JONS October 2014

October 2014 • Vol 5, NO 5

A Focus on the Commission on Cancer INVESTING IN YOUR CAREER AS AN ONCOLOGY NAVIGATOR Lillie D. Shockney, RN, BS, MAS

WHAT YOU NEED TO KNOW ABOUT THE 2015 STANDARDS Frederique H. Evans, MBS

DEVELOPMENT AND EVOLUTION OF AN ONCOLOGY NURSE NAVIGATION PROGRAM Peggy Malone, RN, BS, OCN, and Colleagues

5

YE A R A NNI V E RS A RY

© 2014 Green Hill Healthcare Communications, LLC Navigating Patients Across the Continuum of Cancer Caretm

www.AONNonline.org

PMMP O

ersonalized edicine in Oncology

TM

BIOMARKERS • IMMUNOTHERAPY • TARGETED THERAPIES • DIAGNOSTICS

Providing Critical Insights for Clinical Application Customized Drugs/Biologics Pharmacogenomics Diagnostics & Assays Gene Sequencing Targeted Therapies Immunotherapy Biomarkers Prevention Pathology

www.PersonalizedMedOnc.com GLOBAL BIOMARKERS CONSORTIUM Clinical Approaches to Targeted Technologies ™

The official publication of

www.PersonalizedMedOnc.com GLOBAL BIOMARKERS CONSORTIUM Clinical Approaches to Targeted Technologies ™

WORLD CUTANEOUS MALIGNANCIES CONGRESS

In partnership with PMOElementsAsize30714

™

PMOelementsAsize 40414

LETTERS FROM LILLIE

Editor-in-Chief

Lillie D. Shockney, RN, BS, MAS

Investing in Your Career as an Oncology Navigator It doesn’t matter if you are new at navigation or a seasoned navigator, we each need to invest in our careers. In order to move up the ladder within your current organization, or apply for a promotional position at another institution, we need to demonstrate our commitment to constantly learning new information. Currently, many navigators need to justify their own existence in the position they have, despite the Commission on Cancer standards targeted at requiring that there be a navigation program within the infrastructure of where patients are receiving their cancer diagnosis and treatment.

Why bring this up now as an important topic? Because if you work within a hospital or university health system, it is more than likely you are experiencing a continuation of budget cuts, the first of which are usually targeted at the line item associated with monies for continued staff education. Does that mean you no longer attend conferences or get journal subscriptions or go to other CEU-accredited seminars associated with educating you more about community outreach, navigation, and survivorship? I sure hope not.

It is very important that we all remain abreast of what is happening in our field. So how can you get the education you need? By making a personal investment—as hard as that may seem, it is the smart thing to do. If you are a registered nurse, you probably don’t expect your hospital to pay for your nursing license renewal, right? That is your responsibility. Well, budget cuts that remove funding opportunities for continuing education are now falling into that same category; it is the employee’s responsibility.

Think about it. If there was an easier way to perform a specific navigation task or function, wouldn’t you want to learn about it and make your life a little easier? For those who are the only navigator within their clinical practice, just the concept and opportunity to network with others is a blessing unto itself. And if I were interviewing you for a navigator position and I knew that one candidate had not attended any continuing education programs in the past 2 years while another had paid out of pocket to get to the AONN+ Conference so she could remain up to date on the latest information about navigation, which person do you think I would rank higher for my interview evaluation? That’s right, the one who demonstrated a personal commitment to wanting to further her education, despite it now being an out-of-pocket expense.

Some take-home messages: • When creating your personal budget, factor in dollars for continuing education.

It’s important.

• Those who do invest in their own career growth are the ones who get the higher salaries and better positions because managers recognize this as a quality they want to foster within their organization.

Continued page on 4

Lillie D. Shockney, RN, BS, MAS University Distinguished Service Assoc Prof of Breast Cancer, Depts of Surgery and Oncology; Admin Director, The Johns Hopkins Breast Center; Director, Cancer Survivorship Programs at the Sidney Kimmel Cancer Center at Johns Hopkins; Assoc Prof, JHU School of Medicine, Depts of Surgery, Oncology & Gynecology and Obstetrics; Assoc Prof, JHU School of Nursing shockli@jhmi.edu

Section Editors

Breast Cancer Sharon S. Gentry, RN, MSN, AOCN, CBCN

Breast Health Navigator Novant Health Derrick L. Davis Cancer Center

Cancer Rehabilitation & Survivorship Julie K. Silver, MD Assistant Professor Harvard Medical School

Genetic Counseling

Cristi Radford, MS, CGC Gene Mavens, LLC

Healthcare Disparities Linda Fleisher, PhD, MPH

Asst VP, Office of Health Communications and Health Disparities Asst Prof, Cancer Prevention and Control Fox Chase Cancer Center

Health Promotion and Outreach Iyaad Majed Hasan, DNP, CNP

Director and Nurse Practitioner Survivorship Clinic and Program Cleveland Clinic, Taussig Cancer Center

Patient-Centered Care Mandi Pratt-Chapman, MA Director GW Cancer Institute

Marcy Poletti, RN, MSN

Nursing Operations Supervisor Wake Forest University Baptist Medical Center

Penny Widmaier, RN, MSN Oncology Nurse Navigator Botsford Cancer Center

Prostate Cancer Frank dela Rama, RN, MS, AOCNS

Clinical Nurse Specialist Oncology/Genomics, Cancer Care Clinic Palo Alto Medical Foundation

Thoracic Oncology Pamela Matten, RN, BSN, OCN St. Joseph Hospital

Quality, Outcomes, and Performance Improvement Committee Co-Chairs

Elaine Sein, RN, BSN, OCN, CBCN Danelle Johnston, RN, MSN, OCN, CBCN

Mission Statement

The Journal of Oncology Navi­ gation & Survivorship (JONS) promotes reliance on evidence-based prac­ tices in navigating patients with cancer and their caregivers through diagnosis, treatment, and survivorship. JONS also seeks to strengthen the role of nurse and patient navigators in cancer care by serving as a platform for these professionals to disseminate original research findings, exchange best practices, and find support for their growing community.

JONS-online.com journal of Oncology Navigation & Survivorship

3

LETTERS FROM LILLIE

• Be sure to keep all receipts and record your mileage, as this type of career education is a business expense and, therefore, can usually be included in your annual tax record submissions (include mileage, airport parking, airline fee, hotel fee, food expenses, mileage to and from the airport, registration fee for the conference).

• If you can combine the conference with a family vacation immediately prior to the conference or right after it is completed, you are creating efficiency and value for your dollars being stretched to go even further than perhaps originally planned.

• Be sure to record the conferences, seminars, webinars, educational dinners, etc, you have attended in a continuing education document and maintain this as a running log. Reference those that you flipped the bill to attend. Provide this document as an addendum to your CV.

• Be sure to complete your evaluation forms after attending an educational program so that the presenters get the feedback they need to make sure they have addressed your expectations as well as improve the content for a future presentation.

• If there are special topics of interest that you want AONN+ to focus on that are not being addressed, make our AONN+ leadership team aware so they can be considered for a future educational venue.

• Finally, invest in yourself. You are worth it!

With kind regards,

Lillie D. Shockney, RN, BS, MAS Editor-in-Chief

5

Y E AR A N N I V E RS A RY

A forum for nurse and patient navigators to discuss the day-to-day operations of navigating patients with cancer. The goal is to share ideas and practices and to provide a resource to help navigate patients and improve care.

Join our LinkedIn group today

www.aonnonline.org ABOUT THE COVER

Rainbow Eucalyptus Trees Hawaii Acrylic by a Person Diagnosed with Cancer Artwork from the Lilly Oncology On Canvas: Expressions of a Cancer Journey Art Competition www.LillyOncologyOnCanvas.com The rainbow eucalyptus is a beautiful tree whose outer bark sheds at different rates to reveal the inner bark, which develops over time into jeweled multi-hued tones. Like the natural phenomenon after which it is named, the rainbow eucalyptus reminds us that beneath the neutral surface of the bark or the dark clouds in the sky, lives the promise of hope. After all, it is often after a storm or heavy rain that a rainbow appears. In this way, the rainbow eucalyptus is a symbol of cancer survivorship, just as rainbows are one of mankind’s oldest symbols of hope. Within each survivor lives a strength and beauty that is often revealed under challenging circumstances.

4

october 2014 • Volume 5, number 5

AONNonline.org

You put a lot of work into your treatment plan.

We’ll do everything we can to support it.

Bristol-Myers Squibb Oncology is committed to helping appropriate patients get access to our medications by providing reimbursement support services for healthcare professionals.

Bristol-Myers Squibb Oncology Reimbursement Support It’s your patient. You have our commitment - 100% of requested services are returned to you in 24 hours.*

Access and Reimbursement Services Dedicated, in-person support from local Area Reimbursement Managers Benefit Investigation Prior Authorization and Appeals Support Secure provider portal for monitoring reimbursement cases

*Access Support enrollment form must be complete and have all required signatures.

1

Patient Affordability Services Choosing the appropriate therapy is the first step. Helping patients pay for it is another matter. BMS Access Support® can assist with reimbursement and co-pay issues.

Here’s how: Eligible, commercially-insured patients pay a $25 co-pay per infusion up to $25,000 per year per product Patients with insurance through Federal Healthcare Programs or patients that are otherwise underinsured or uninsured are referred to independent charitable organizations that may be able to provide assistance

On The Phone, Online, In Person For more details, visit www.BMSAccessSupport.com or call 1-800-861-0048.

©2014 Bristol-Myers Squibb Company. MMUS14UB00877-01-01 07/14 Access Support and Access Support logo are registered trademarks of Bristol-Myers Squibb Company.

PUBLISHING STAFF Senior Vice President/Group Publisher Nicholas Englezos nenglezos@the-lynx-group.com Senior Vice President, Sales & Marketing Philip Pawelko ppawelko@the-lynx-group.com Vice President/Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Group Director, Sales & Marketing John W. Hennessy jhennessy2@the-lynx-group.com Publishers Russell Hennessy rhennessy@the-lynx-group.com Cristopher Pires cpires@the-lynx-group.com Director, Client Services Lou Lesperance, Jr llesperance@the-lynx-group.com Editorial Director Frederique H. Evans, MBS fevans@the-lynx-group.com Copy Editor Rosemary Hansen Senior Production Manager Lynn Hamilton

THE LYNX GROUP President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Human Resources Jennine Leale Associate Director, Content Strategy & Development John Welz Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistant Lora LaRocca Director, Digital Media Anthony Romano Web Content Managers David Maldonado Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Sangenito Senior Project Manager Jini Gopalaswamy Project Coordinators Mike Kodada Deanna Martinez IT Specialist Carlton Hurdle Executive Administrator Rachael Baranoski Office Coordinator Robert Sorensen Green Hill Healthcare Communications, LLC 1249 South River Road - Ste 202A • Cranbury, NJ 08512 Phone: 732.656.7935 • Fax: 732.656.7938

6

october 2014 • Volume 5, number 5

Table of ConTents

october 2014 • Vol 5, NO 5

LETTERS FROM LILLIE

3 Investing in Your Career as an Oncology Navigator Lillie D. Shockney, RN, BS, MAS

A focus on the Commission on cancer

9

What You Need to Know About the 2015 Standards

Frederique H. Evans, MBS

QUALITY, OUTCOMES, AND PERFORMANCE IMPROVEMENT (QOPI) COMMITTEE

12

Jennifer R. Klemp, PhD, MPH, MA

THE NATIONAL COMPREHENSIVE CANCER NETWORK

14

Navigation as a Tool for Quality Improvement Sharon Gentry, RN, MSN, AOCN, CBCN

NURSE NAVIGATion PROGRAM

19 Development and Evolution of an Oncology Nurse Navigation Program: From Formation to Fruition Peggy Malone, RN, BS, OCN; Lisa Bruno, RN, BSN, OCN; Beth Hayden, RN, BSN, MBA, OCN; Julie Carlson, RN, MSN, APN, AOCNS BREAST CANCER COLLABORATIVE REGISTRY

29 Breast Cancer Collaborative Registry: Comparison of Physical and Mental Health and Sleep in Breast Cancer Survivors Constance Visovsky, PhD, RN, ACNP-BC; Ann M. Berger, PhD, APRN, AOCNS, FAAN; Melody Hertzog, PhD; Janique Rice, MS; Marcia Y. Shade, MS, RN THE PATIENT’S VOICE

40

Practice Makes Not Perfect: Striving After Cancer Carolyn Comeau

CLINICAL TRIAL TRACKER

44

New Clinical Trials Under Way

Patient Assistance Programs

46

Imbruvica YOU&i Access Program and Support for Patients

Journal of Oncology Navigation & Survivorship, ISSN 2166-0999 (print); ISSN 2166-0980 (online), is published 6 times a year by Green Hill Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Telephone: 732.656.7935. Fax: 732.656.7938. Copy­right © 2014 by Green Hill Health­care Com­muni­cations, LLC. All rights reserved. Journal of Oncology Navigation & Survivorship logo is a registered trademark of Green Hill Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the publisher. Printed in the United States of America.

EDITORIAL CORRESPONDENCE should be ad­­dressed to EDITORIAL DEPARTMENT, Journal of Oncology Navigation & Survivorship (JONS), 1249 South River Road, Suite 202A, Cranbury, NJ 08512. E-mail: fevans@the-lynx-group.com. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $50.00; institutions, $90.00; single issues, $5.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subject to change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPART­MENT, Green Hill Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. The ideas and opinions expressed in JONS do not necessarily reflect those of the editorial board, the editorial director, or the publisher.

Publication of an advertisement or other product mentioned in JONS should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the editorial board nor the publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other healthcare professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribing physician. Please convey any errors to the editorial director.

AONNonline.org

IN PLANNING DURATION OF THERAPY WITH VELCADE® (bortezomib)

WHAT MORE CAN YOU DO FOR YOUR PATIENTS WITH MULTIPLE MYELOMA?

An online resource—created just for nurses—is available to help you do more to manage your patients’ treatment.

The VELCADE (bortezomib) Nurse Portal features: ▼

Patient education tools to help support your patients throughout their journey with multiple myeloma

▼

A learning center to help you and your patients get the most out of their treatment

▼

Case studies to support you in managing different clinical scenarios

Start learning more today at www.VELCADE-RN.com

INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR VELCADE® (bortezomib) INDICATIONS VELCADE (bortezomib) is indicated for the treatment of patients with multiple myeloma. VELCADE is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy.

CONTRAINDICATIONS VELCADE is contraindicated in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol, including anaphylactic reactions. VELCADE is contraindicated for intrathecal administration. Fatal events have occurred with intrathecal administration of VELCADE. WARNINGS, PRECAUTIONS, AND DRUG INTERACTIONS ▼ Peripheral neuropathy: Manage with dose modification or discontinuation. Patients with preexisting severe neuropathy should be treated with VELCADE only after careful riskbenefit assessment. ▼ Hypotension: Use caution when treating patients taking antihypertensives, with a history of syncope, or with dehydration. ▼ Cardiac toxicity: Worsening of and development of cardiac failure have occurred.

Closely monitor patients with existing heart disease or risk factors for heart disease. ▼ Pulmonary toxicity: Acute respiratory syndromes have occurred. Monitor closely for new or worsening symptoms. ▼ Posterior reversible encephalopathy syndrome: Consider MRI imaging for onset of visual or neurological symptoms; discontinue VELCADE if suspected.

Gastrointestinal toxicity: Nausea, diarrhea, constipation, and vomiting may require use of antiemetic and antidiarrheal medications or fluid replacement. ▼ Thrombocytopenia or Neutropenia: Monitor complete blood counts regularly throughout treatment. ▼ Tumor lysis syndrome: Closely monitor patients with high tumor burden. ▼ Hepatic toxicity: Monitor hepatic enzymes during treatment. ▼ Embryo-fetal risk: Women should avoid becoming pregnant while being treated with VELCADE. Advise pregnant women of potential embryo-fetal harm. ▼ Closely monitor patients receiving VELCADE in combination with strong CYP3A4 inhibitors.

Avoid concomitant use of strong CYP3A4 inducers.

ADVERSE REACTIONS Most commonly reported adverse reactions (incidence ≥20%) in clinical studies include nausea, diarrhea, thrombocytopenia, neutropenia, peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, constipation, vomiting, lymphopenia, rash, pyrexia, and anorexia. ▼

Please see Brief Summary for VELCADE on the next page of this advertisement.

S:7”

Brief Summary

VELC3X0043_A_Velcade_BS_7x10_r3.indd 1

Embryo-fetal: Pregnancy Category D. Women of reproductive potential should avoid becoming pregnant while being treated with VELCADE. Bortezomib administered to rabbits during organogenesis at a dose approximately 0.5 times the clinical dose of 1.3 mg/m2 based on body surface area caused post-implantation loss and a decreased number of live fetuses.

ADVERSE EVENT DATA: Safety data from phase 2 and 3 studies of single-agent VELCADE 1.3 mg/m2/dose administered intravenously twice weekly for 2 weeks followed by a 10-day rest period in 1163 patients with previously-treated multiple myeloma (N=1008) and previously-treated mantle cell lymphoma (N=155) were integrated and tabulated. In these studies, the safety profile of VELCADE was similar in patients with multiple myeloma and mantle cell lymphoma.

In the integrated analysis, the most commonly reported (≥10%) adverse reactions were nausea (49%), diarrhea NOS (46%), fatigue (41%), peripheral neuropathies NEC (38%), thrombocytopenia (32%), vomiting NOS (28%), constipation (25%), pyrexia (21%), anorexia (20%), anemia NOS (18%), headache NOS (15%), neutropenia (15%), rash NOS (13%), paresthesia (13%), dizziness (excl vertigo 11%), and weakness (11%). Eleven percent (11%) of patients experienced at least 1 episode of ≥Grade 4 toxicity, most commonly thrombocytopenia (4%) and neutropenia (2%). A total of 26% of patients experienced a serious adverse reaction during the studies. The most commonly reported serious adverse reactions included diarrhea, vomiting, and pyrexia (3% each), nausea, dehydration, and thrombocytopenia (2% each), and pneumonia, dyspnea, peripheral neuropathies NEC, and herpes zoster (1% each).

In the phase 3 VELCADE+melphalan and prednisone study in previously untreated multiple myeloma, the safety profile of VELCADE administered intravenously in combination with melphalan/prednisone is consistent with the known safety profiles of both VELCADE and melphalan/prednisone. The most commonly reported adverse reactions in this study (VELCADE+melphalan/prednisone vs melphalan/prednisone) were thrombocytopenia (48% vs 42%), neutropenia (47% vs 42%), peripheral neuropathy (46% vs 1%), nausea (39% vs 21%), diarrhea (35% vs 6%), neuralgia (34% vs <1%), anemia (32% vs 46%), leukopenia (32% vs 28%), vomiting (26% vs 12%), fatigue (25% vs 14%), lymphopenia (23% vs 15%), constipation (23% vs 4%), anorexia (19% vs 6%), asthenia (16% vs 7%), pyrexia (16% vs 6%), paresthesia (12% vs 1%), herpes zoster (11% vs 3%), rash (11% vs 2%), abdominal pain upper (10% vs 6%), and insomnia (10% vs 6%).

In the phase 3 VELCADE subcutaneous vs intravenous study in relapsed multiple myeloma, safety data were similar between the two treatment groups. The most commonly reported adverse reactions in this study were peripheral neuropathy NEC (37% vs 50%), thrombocytopenia (30% vs 34%), neutropenia (23% vs 27%), neuralgia (23% vs 23%), anemia (19% vs 23%), diarrhea (19% vs 28%), leukopenia (18% vs 20%), nausea (16% vs 14%), pyrexia (12% vs 8%), vomiting (9% vs 11%), asthenia (7% vs 16%), and fatigue (7% vs 15%). The incidence of serious adverse reactions was similar for the subcutaneous treatment group (20%) and the intravenous treatment group (19%). The most commonly reported SARs were pneumonia and pyrexia (2% each) in the subcutaneous treatment group and pneumonia, diarrhea, and peripheral sensory neuropathy (3% each) in the intravenous treatment group.

DRUG INTERACTIONS: Bortezomib is a substrate of cytochrome P450 enzyme 3A4, 2C19 and 1A2. Co-administration of ketoconazole, a strong CYP3A4 inhibitor, increased the exposure of bortezomib by 35% in 12 patients. Monitor patients for signs of bortezomib toxicity and consider a bortezomib dose reduction if bortezomib must be given in combination with strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir). Co-administration of omeprazole, a strong inhibitor of CYP2C19, had no effect on the exposure of bortezomib in 17 patients. Co-administration of rifampin, a strong CYP3A4 inducer, is expected to decrease the exposure of bortezomib by at least 45%. Because the drug interaction study (n=6) was not designed to exert the maximum effect of rifampin on bortezomib PK, decreases greater than 45% may occur. Efficacy may be reduced when VELCADE is used in combination with strong CYP3A4 inducers; therefore, concomitant use of strong CYP3A4 inducers is not recommended in patients receiving VELCADE. St. John’s wort (Hypericum perforatum) may decrease bortezomib exposure unpredictably and should be avoided. Co-administration of dexamethasone, a weak CYP3A4 inducer, had no effect on the exposure of bortezomib in 7 patients. Co-administration of melphalan-prednisone increased the exposure of bortezomib by 17% in 21 patients. However, this increase is unlikely to be clinically relevant.

USE IN SPECIFIC POPULATIONS: Nursing Mothers: It is not known whether bortezomib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from VELCADE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: The safety and effectiveness of VELCADE in children has not been established.

Geriatric Use: No overall differences in safety or effectiveness were observed between patients ≥age 65 and younger patients receiving VELCADE; but greater sensitivity of some older individuals cannot be ruled out.

Patients with Renal Impairment: The pharmacokinetics of VELCADE are not influenced by the degree of renal impairment. Therefore, dosing adjustments of VELCADE are not necessary for patients with renal insufficiency. Since dialysis may reduce VELCADE concentrations, VELCADE should be administered after the dialysis procedure. For information concerning dosing of melphalan in patients with renal impairment, see manufacturer’s prescribing information.

Patients with Hepatic Impairment: The exposure of bortezomib is increased in patients with moderate and severe hepatic impairment. Starting dose should be reduced in those patients.

Patients with Diabetes: During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving VELCADE treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication.

Please see full Prescribing Information for VELCADE at VELCADEHCP.com.

VELCADE, MILLENNIUM and are registered trademarks of Millennium Pharmaceuticals, Inc. Other trademarks are property of their respective owners.

Millennium Pharmaceuticals, Inc., Cambridge, MA 02139 Copyright © 2013, Millennium Pharmaceuticals, Inc. All rights reserved. Printed in USA V-14-0087a Printed in USA 4/14

8/27/13 4:54 PM

S:10”

INDICATIONS: VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with multiple myeloma. VELCADE for Injection is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy.

CONTRAINDICATIONS: VELCADE is contraindicated in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol, including anaphylactic reactions. VELCADE is contraindicated for intrathecal administration. Fatal events have occurred with intrathecal administration of VELCADE. WARNINGS AND PRECAUTIONS: Peripheral Neuropathy: VELCADE treatment causes a peripheral neuropathy that is predominantly sensory; however, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with pre-existing symptoms (numbness, pain, or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including ≥Grade 3) during treatment with VELCADE. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness. In the Phase 3 relapsed multiple myeloma trial comparing VELCADE subcutaneous vs intravenous, the incidence of Grade ≥2 peripheral neuropathy events was 24% for subcutaneous and 39% for intravenous. Grade ≥3 peripheral neuropathy occurred in 6% of patients in the subcutaneous treatment group, compared with 15% in the intravenous treatment group.

Starting VELCADE subcutaneously may be considered for patients with pre-existing or at high risk of peripheral neuropathy.

Patients experiencing new or worsening peripheral neuropathy during VELCADE therapy may require a decrease in the dose and/or a less dose-intense schedule. In the VELCADE vs dexamethasone phase 3 relapsed multiple myeloma study, improvement in or resolution of peripheral neuropathy was reported in 48% of patients with ≥Grade 2 peripheral neuropathy following dose adjustment or interruption. Improvement in or resolution of peripheral neuropathy was reported in 73% of patients who discontinued due to Grade 2 neuropathy or who had ≥Grade 3 peripheral neuropathy in the phase 2 multiple myeloma studies. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma.

Hypotension: The incidence of hypotension (postural, orthostatic, and hypotension NOS) was 8%. These events are observed throughout therapy. Caution should be used when treating patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated. Management of orthostatic/postural hypotension may include adjustment of antihypertensive medications, hydration, and administration of mineralocorticoids and/or sympathomimetics.

Cardiac Toxicity: Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have occurred during VELCADE therapy, including reports in patients with no risk factors for decreased left ventricular ejection fraction. Patients with risk factors for, or existing, heart disease should be closely monitored. In the relapsed multiple myeloma study of VELCADE vs dexamethasone, the incidence of any treatment-related cardiac disorder was 8% and 5% in the VELCADE and dexamethasone groups, respectively.

The incidence of adverse reactions suggestive of heart failure (acute pulmonary edema, pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock) was ≤1% for each individual reaction in the VELCADE group. In the dexamethasone group, the incidence was ≤1% for cardiac failure and congestive cardiac failure; there were no reported reactions of acute pulmonary edema, pulmonary edema, or cardiogenic shock. There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established.

Pulmonary Toxicity: Acute Respiratory Distress Syndrome (ARDS) and acute diffuse infiltrative pulmonary disease of unknown etiology, such as pneumonitis, interstitial pneumonia, and lung infiltration have occurred in patients receiving VELCADE. Some of these events have been fatal.

In a clinical trial, the first two patients given high-dose cytarabine (2 g/m2 per day) by continuous infusion with daunorubicin and VELCADE for relapsed acute myelogenous leukemia died of ARDS early in the course of therapy. There have been reports of pulmonary hypertension associated with VELCADE administration in the absence of left heart failure or significant pulmonary disease.

In the event of new or worsening cardiopulmonary symptoms, consider interrupting VELCADE until a prompt, comprehensive, diagnostic evaluation is conducted.

Posterior Reversible Encephalopathy Syndrome (PRES): Posterior Reversible Encephalopathy Syndrome (PRES; formerly termed Reversible Posterior Leukoencephalopathy Syndrome (RPLS)) has occurred in patients receiving VELCADE. PRES is a rare, reversible, neurological disorder, which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. Brain imaging, preferably MRI (Magnetic Resonance Imaging), is used to confirm the diagnosis. In patients developing PRES, discontinue VELCADE. The safety of reinitiating VELCADE therapy in patients previously experiencing PRES is not known.

Gastrointestinal Toxicity: VELCADE treatment can cause nausea, diarrhea, constipation, and vomiting, sometimes requiring use of antiemetic and antidiarrheal medications. Ileus can occur.

Fluid and electrolyte replacement should be administered to prevent dehydration. Interrupt VELCADE for severe symptoms.

Thrombocytopenia/Neutropenia: VELCADE is associated with thrombocytopenia and neutropenia that follow a cyclical pattern, with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle. The cyclical pattern of platelet and neutrophil decreases and recovery remained consistent over the 8 cycles of twice-weekly dosing, and there was no evidence of cumulative thrombocytopenia or neutropenia. The mean platelet count nadir measured was approximately 40% of baseline.

The severity of thrombocytopenia was related to pretreatment platelet count. In the relapsed multiple myeloma study of VELCADE vs dexamethasone, the incidence of bleeding (≥Grade 3) was 2% on the VELCADE arm and <1% on the dexamethasone arm. Complete blood counts (CBC) should be monitored frequently during treatment with VELCADE. Platelet counts should be monitored prior to each dose of VELCADE. Patients experiencing thrombocytopenia may require change in the dose and schedule of VELCADE. Gastrointestinal and intracerebral hemorrhage has been reported in association with VELCADE. Transfusions may be considered.

Tumor Lysis Syndrome: Tumor lysis syndrome has been reported with VELCADE therapy.

Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment.

Monitor patients closely and take appropriate precautions.

Hepatic Toxicity: Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Other reported hepatic reactions include hepatitis, increases in liver enzymes, and hyperbilirubinemia. Interrupt VELCADE therapy to assess reversibility. There is limited re-challenge information in these patients.

A focus on the Commission on cancer

What You Need to Know About the 2015 Standards Frederique H. Evans, MBS, Editorial Director, JONS

W

ith the latest Commission on Cancer (CoC) standards taking effect in January 2015, cancer centers across the United States are in various stages of compliance. Altogether, the commission has accredited approximately 1500 cancer programs and more than 70% of patients with cancer are being treated at a CoC-accredited program.1 In an effort to provide you with the latest information on these standards, the Journal of Oncology Navigation & Survivorship (JONS) has dedicated this issue of the journal to the CoC and its standards. In this article, we had the opportunity to discuss key opportunities and issues facing cancer centers seeking accreditation with members of the CoC governance, and learn more about the commission.

Patient-Centered Care

The CoC was founded in 1922 under the authority of the American College of Surgeons and is led by volunteer leaders that are nominated and elected for the positions of leadership. With the new standards, the commission is seeking to improve quality of life and survival for patients with cancer.

“Several years ago, we looked at our standards,” Daniel P. McKellar, MD, FACS, Chair of the CoC, told JONS. “We also looked at some important documents, like the Institute of Medicine reports on cancer care, as well as healthcare in this country. They made a very strong argument that healthcare in this country really isn’t patient-centered, like it should be.”

In particular, the report, provided strong support for survivorship care, patient navigation, palliative care, and psychosocial distress management. To address these gaps of care, members of the commission, completely revised the standards and included 3 new patient-centered standards, which became effective in January 2012. The new standards included establishing a patient navigation process (3.1), screening patients for psychosocial distress (3.2), and creating a survivorship care plan (3.3).2 The CoC allowed for a phase-in period for these standards and requested that cancer programs show how they are working to meet the standards during a 3-year span from 2012 to 2015, at which point the standards would take effect.

“The programs have done pretty well,” according to Dr McKellar. “I think their standards have done a lot to gen-

erate a lot of activity in the United States around areas like patient navigation, survivorship, and management of psychosocial distress.”

Providing, Advocating for Quality of Care

Over the years, the commission has evolved its accreditation standards to match the current state of cancer care, according to Lawrence Shulman, MD, Chair of the Quality Integration Committee. For example, the committee manages the National Cancer Database (NCD) —a compilation of registry data from all other CoC-accredited hospitals.

I think their standards have done a lot to generate a lot of activity in the United States around areas like patient navigation, survivorship, and management of psychosocial distress.

In addition, the Committee consists of several subcommittees that develop new quality measures that can be evaluated from the NCD database, and provide reports to each CoC-accredited hospital with their data and data from the overall CoC database to help hospitals better understand how they are performing in many of the quality metrics. Another subcommittee oversees research programs performed through the CoC and the NCD. The CoC also has a reach in Washington, and is currently involved in several major initiatives, according to James J. Hamilton, Jr, MD, FACS, Chair of the Advocacy Committee. Because one of the CoC standards includes enrolling patients in clinical trials, the commission is also lobbying to increase National Institutes of Health funding.

“What the CoC brings to the table, for congress or for anyone, is that we have all 1500 programs that are organized in ways that can participate in research and that are encouraged because of our standards to do so,” Dr Hamilton explained. “The value to the government is that when you have that system in place, it doesn’t really cost them a dime that can facilitate this research.”

On the state level, the commission has also been very active in cancer control programs. Specifically, members of the commission are promoting the importance of survivor-

JONS-online.com journal of Oncology Navigation & Survivorship

9

2015 standards

ship issues, navigation in the cancer process, and helping the stress reduction in patients in accordance with the CoC standards.

Getting Started

CoC accreditation comes with a wide range of benefits, including national recognition as having established performance measures for the provision of high-quality of cancer care.3 Accredited institutions also have the benefit of quality improvement measures such as participating in the NCD and access to Comparison Benchmark Reports.

There is also the benefit of organized care, data analysis, and public awareness.

The programs truly have to be showing compliance.

For centers considering accreditation, the CoC offers a wide range of resources to get the process started. “We have a unique opportunity to effect change in those cancer programs,” Dr McKellar explained. “We have to also be sensitive to resource availability, and we know that in most hospitals around the country, resources really are dwindling. That’s why we provide a lot of support to our cancer programs to help them meet the standard.” The CoC website also provides a series of best practices, including tools for cancer programs as well as examples of how other cancer programs are meeting those standards. Webinars and face-to-face webinars are also available (see, eo2.commpartners.com/users/acsnew/search.php).

In addition, the Academy of Oncology Nurse & Patient Navigators Fifth Annual Conference will be offering several sessions focusing on the standards, including “Commission on Cancer Updates” (Friday, September 19, at 8 am) and “Navigation and Survivorship Standards – Are You Ready for Your Commission on Cancer Accreditation?”

(Saturday, September 20, 2014 , at 10 am).

There is also a wealth of information available on YouTube, including videos on “CoC Distress Screening Quality Care Standard” (see, http://youtube/yulicgrxKnY) and “Accreditations for Cancer Care More Than Just CoC” (see, http://youtube/UB2SEvjWi8Q).

Surveyors

Overall, the CoC has a team of approximately 50 surveyors, which is overseen by the Field Staff Subcommittee. “The role of the surveyor is very, very important,” Dr McKellar emphasized. “The American College of Surgeons has many quality programs and part of our philosophy is that we want to provide meaningful standards, we want to collect rigorous data, and we want to verify that

10

october 2014 • Volume 5, number 5

cancer programs are truly meeting the standards.” To that end, the surveyors go out onsite, and every 3 years, they visit each cancer program.

A surveyor visit is a full-day meeting, where they review the standards with the cancer programs. “We like to think of our surveyors more as consultants,” Dr McKellar explained. “They are really going out and looking deeply into the cancer programs trying to identify opportunities for improvements.” During their visit, the surveyors also bring ideas from previous cancer centers they surveyed, as well as share best practices and various tools.

Onsite visits are key to verifying compliance with the standards. In addition, as part of the accreditation process, all CoC-accredited programs have to submit comprehensive data on every patient treated in their program for the NCD. These data are used to ensure quality improvement, and cancer programs have to show compliance within a threshold for each specific measure set by the CoC. The process is transparent, and the surveyors have an open communication with the centers to identify deficiencies or opportunities for improvement. “When I, as a surveyor, go and visit a program,” Dr McKellar said. “If I see that they’re not meeting certain standards in my summation I will tell the cancer program, ‘You’re not meeting this standard. Here’s what I recommend.’”

The CoC has a system of deficiency resolutions in place to resolve all areas needing improvement within 1 year, at which point cancer centers need to submit documentation showing that they are resolved. A program can have up to 7 deficiencies of approximately 34 standards, and still maintain their accreditation until they are resolved, according to Dr McKellar. If a program has more than 7 deficiencies, they receive nonaccreditation and have to restart the process.

“The programs truly have to be showing compliance,” Dr McKellar stated. “If they’re not in compliance with more than 7 standards, we consider them nonaccreditation, and we encourage them to have a consultant come in and assist their program.” The CoC works with a team of CoC-trained consultants, who are independent and not employed by the commission. These services may be especially useful for new centers just starting out. Although these consultants are not mandated by the commission, they are a great resource for cancer centers working toward becoming accredited.

Joining the Team of Surveyors

Both physicians and nonphysicians can become a surveyor. To become a surveyor, candidates should be actively practicing medicine for a CoC-accredited cancer program or recently retired.4 Retired physicians may be considered if their retirement began less than 1 year before the appli-

AONNonline.org

A focus on the Commission on cancer

cation date. Nonphysicians should have recognized experience and service in oncology administration for a CoC-accredited cancer program as well as significant operational knowledge regarding Tumor Registry.

Once an application is submitted, the candidate undergoes an interview with the Field Staff Subcommittee chair.

Selected candidates are trained and undergo a 1-day orientation in August, followed by a 2-day surveyor training in November. Upon completion, the surveyor receives their survey assignments, which begins in January of the following year. The new surveyor is also required to go on an observation with an experienced surveyor, Dr McKellar explained, and is assigned a mentor. The mentor helps train them, answer their questions, and goes with the new surveyor when they perform their first survey.

Barriers to Accreditation

Cancer centers that are working on integrating the standards are facing several key barriers, including understanding the standards, finding the best ways to implement them, as well as finding the budget to do so.

The CoC standards do not provide a step-by-step guide on how to implement a navigation program or psychosocial stress test. They leave room for creativity on the part of the cancer center. Stephen B. Edge, MD, FACS, Chair of the Nominating Committee, explained that at his center, which includes a 14-hospital network with 6 cancer center buildings, 5500 new analytics cases annually, and 25 to 30 medical oncologists who are distributed over a 250mile radius, it is not feasible to include a genetic counselor in every center. However, to meet this challenge, they are looking to implement video consultation for genetics, which has been shown to be equally effective with in-person counseling. “There is plenty of room for creativity with quality standards,” he added. “As any time, you have a creative process going on, it doesn’t always work out the way you expect. You recognize it and you try something different.”

According to the LIVESTRONG survey results he continued, the navigation standards were best understood, followed by the distress assessment, then survivorship standards. “How to functionally implement a distress assessment tool and deal with the results of it is not a trivial activity for any center,” Dr Shulman explained. “The larger you are, the more complex it is.” Once the standard is implemented, it needs to be evaluated, and centers need to be able to manage patients who have a high level of distress. “Not every program is currently staffed to manage that.” The survivorship standard is currently being reevaluated and it is possible that the time and the components of that standard will change before they become effective in January.

The survivorship standard is more vague in terms of the appropriate patient population that it applies to, whether everyone needs a survivorship care plan or just patient treated with curative intent; is it patients with all diseases or just the common diseases; what data components should be in the treatment summary and survivorship care plan. “There is no consensus on that,” according to Dr Shulman.

There is plenty of room for creativity with quality standards.

Other concerns raised by these standards are the costs associated with accreditation. Specifically, the application fee is $1000; annual maintainance, $1500; the survey, $7500; and survey cancellation is $1000.5 These fees do not include the cost of hiring staff to meet each of the standards.

Conclusion

If you are lucky enough to have just gone through this process, you may not be in the hot seat until 2016 or 2017, but putting these standards on the back burner, will not be beneficial for your patients or your center. If, however, you are looking to get the process started, keep in mind that you are not alone and there are resources available to you.

When learning about the standards, consider asking the following questions: what do the standards really mean; what does it really mean when you operationalize it; does it get measured one time or do you have to incorporate it into every visit; what do we mean by the survivorship care plan standards; and how are we going to support the implementation of survivorship care plans around hospitals?

In the end, centers owe it to themselves and their patients to meet these standards, Dr Edge told JONS. “The important point is that people are not implementing these standards, simply to assure that they remain accredited. People are implementing the standards, because they will improve the patient experience and the outcome of cancer care.” g

References

1. American College of Surgeons. About the CoC Accreditation. www.facs. org/quality-programs/cancer/accredited/about. Accessed September 2, 2014.

2. American College of Surgeons. Cancer Program Standards 2012. www.facs. org/quality%20programs/cancer/coc/standards. Accessed August 28, 2014.

3. Benefits of Being a CoC-Accredited Program. www.facs.org/quality-programs/cancer/accredited/benefitscoc. Accessed September 2, 2014.

4. The American College of Surgeons. January 2013 Introducing the CoC Source. www.facs.org/publications/newsletters/coc-source/2013/jan- 2013-introsource. Accessed August 28, 2014.

5. American College of Surgeons. Fees. www.facs.org/quality-programs/ cancer/accredited/benefitscoc/fees. Accessed September 2, 2014.

JONS-online.com journal of Oncology Navigation & Survivorship

11

Quality, outcomes, and performance improvement (QOPI) committee

Jennifer R. Klemp, PhD, MPH, MA

Associate Professor of Medicine, Division of Clinical Oncology, Director, Cancer Survivorship, Cancer Risk Counselor, University of Kansas Cancer Center; Founder, CEO, Cancer Survivorship Training, Inc.

J

ust like many other nurse navigators, there was a pivotal time in my life when I knew I wanted to dedicate my career to cancer. As a young, altruistic senior in college, I was set to attend medical school, become a surgeon (yes, this is what I really wanted to do) and save the world. Unfortunately, life does not always go as planned and you have to take these as opportunities to truly define who you are and what path you will follow.

The Moment That Changed My Life

I can still clearly remember that day 23 years ago. It was April, and I was studying for finals during the last semester of my senior year in college. My mother, who was undergoing imaging twice a year for fibrocystic breasts, called to let me know she was having a biopsy, and told me not to worry. But the first thing you do is worry! Something felt wrong, and I decided to drive home and be there when my parents returned from the procedure. They walked in the door, both looking sad and defeated, and all I could do was hug them and cry.

My mother was 49 years old at the time and had endocrine-negative lobular breast cancer in the left breast with 18 positive nodes. That is enough to knock the optimism out of you. My mother was given several treatment options: mastectomy followed by 6 cycles of chemotherapy (neoadjuvant therapy was not an option at the time), radiation, and, because physicians thought she had a 75% chance of dying in the next 5 years, another treatment option she had to consider was a bone marrow transplant. Unfortunately, when these options were laid out before her, all she heard was “you have a 25% chance of still being alive in 5 years,” so she decided to get a bone marrow transplant. As a family, we supported her decision but also sought second, third, and fourth opinions. We also looked at transplant programs and clinical trials across the country. The Internet was not a resource at the time, and this process involved a lot of phone calls and office visits.

Because I was just graduating, I was ideally suited to take a year off and care for my mother during her journey, which included 3 months of an inpatient transplant protocol at the University of Nebraska. On October 31, 1994, my mother was started on high-dose chemotherapy and I became her navigator. Taking my job very seriously, I double-checked everything, did research at the library, and had

12

october 2014 • Volume 5, number 5

a stationary bike brought into her room—I would hold her on it so she could peddle. I also fed her Dove bars, which is all she could eat at the time.

Caring for my mother changed that year of my life.

Transitioning to a Lifelong Vocation

After 1 year of treatment, she was ready to get her life back, and resumed teaching high school biology the following year. She was ready to move on, but my transition was not so easy. My life plan had changed and I wrote a letter to my now mentor, Carol Fabian, MD, from the University of Kansas Medical Center, and told her that I wanted to work in breast cancer research. “If you do not have any money to pay me, that’s OK,” I wrote. “I will figure it out.” To this day, she still has this letter. She has been my mentor for almost 2 decades, and together, we make a formidable team.

These leaders in breast cancer motivated me and taught me invaluable life and career lessons.

I did complete my education in a nontraditional way, working full time and completing 3 advanced degrees from the University of Kansas. I had the amazing opportunity to work with several strong women mentors, in addition to Dr Fabian. I also helped build the Breast Cancer Prevention Program at the University of California, San Francisco with Laura J. Esserman, MD, MBA. These leaders in breast cancer motivated me and taught me invaluable life and career lessons.

Improving Access to Quality Care

Today, my mother continues to thrive and be the source of my motivation to improve access to quality care for cancer survivors. With the Commission on Cancer (CoC) standards looming, my journey has prepared me to help my organization meet the standards: 3.1, patient navigation process; 3.2, psychosocial distress screening; and 3.3, survivorship care plan.

My role at the University of Kansas Cancer Center, a National Cancer Institute–designated center, includes being an Associate Professor of Medicine, Division of

AONNonline.org

A focus on the Commission on cancer

Clinical Oncology, the Director of Cancer Survivorship, a cancer risk counselor, and an entrepreneur as the founder and CEO of Cancer Survivorship Training, Inc. These clinical, research, and entrepreneurial hats provide me with the access to help our organization meet national benchmarks to ensure quality care to our patients and their caregivers. This task is daunting and sometimes feels impossible.

My philosophy focuses on how to improve the quality and quantity of life for cancer survivors from the time of diagnosis to the rest of their lives. The CoC standards push us to integrate best practices. This sometimes feels like an impossible task to undertake, especially with shrinking resources, the sheer volume of the different moving parts in the clinical workflow, as well as the limited functionality of electronic health records to include navigation notes, pa-

tient-reported outcomes (eg, distress screening), or building survivorship care plans. The functionality of health records is changing, but not in time for 2015.

AONN+

I am the most recent member of the Academy of Oncology Nurse & Patient Navigators (AONN+) Leadership Council, with the expanded focus on survivorship.

AONN+ is well-suited and has taken on the challenge to facilitate the sharing of best practices and providing resources to help each of us meet our responsibilities. I am honored to be part of such a forward-thinking organization as AONN+ and feel it is consistent with my career path.

Thank you for letting me share my journey and hope we will continue to collaborate with the goal of improving the quality and quantity of life for cancer survivors. g

REGISTER TODAY! WCMC CONFERENCE CHAIR

Sanjiv S. Agarwala, MD

THIRD ANNUAL CONFERENCE

WORLD CUTANEOUS MALIGNANCIES CONGRESS

™

OCT. 29 - OCT. 31, 2014

www.regonline.com/WCMC2014

WORLD THIRD ANNUAL CONFERENCE CUTANEOUS GLOBAL BIOMARKERS MALIGNANCIES CONSORTIUM Clinical Approaches to Targeted Technologies CONGRESS

Professor of Medicine Temple University School of Medicine Chief, Medical Oncology & Hematology St. Luke’s Cancer Center Bethlehem, PA

GBC CONFERENCE CHAIRS Jorge E. Cortes, MD

Chair, CML and AML Sections D.B. Lane Cancer Research Distinguished Professor for Leukemia Research Department of Leukemia Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX

TM

™

TM

OCT. 31 - NOV. 1, 2014

www.regonline.com/GBC2014

Roy S. Herbst, MD, PhD

Ensign Professor of Medicine Professor of Pharmacology Chief of Medical Oncology Director, Thoracic Oncology Research Program Associate Director for Translational Research Yale Cancer Center New Haven, CT

Marriott Marquis San Francisco • San Francisco, California WCMC GBC2014RegisterToday_21214

JONS-online.com journal of Oncology Navigation & Survivorship

13

The national comprehensive cancer network

Navigation as a Tool for Quality Improvement Sharon Gentry, RN, MSN, AOCN, CBCN

T

he National Comprehensive Cancer Network (NCCN) provides clinical practice guidelines in oncology for all types and stages of cancer as well as areas of supportive care. The guidelines are updated annually and allow new findings to be initiated quickly. They have become a benchmark as the best standard of care in the United States and internationally. Concordance of care is provided in an annual report for each participating institution. One hundred percent is not expected since the clinical situations involve the human nature of diseaseâ&#x20AC;&#x201D; comorbidities, patient choices, and cultural values. Beyond treatment care, there was a lot of variation in practice patterns. The variation in care among the centers drove the NCCN to initiate Opportunities for Improvement.

Breast cancer care was chosen as the project for institutions to identify and address quality issues. Some chose process-oriented projects while others selected guideline-targeted practices. Interestingly, navigation was used as a tool in 3 of the opportunities.

The use of navigation has led to a 74% retention rate after the first visit, and the time from call to first appointment has been reduced from 14 to 21 days to 7 days.

Northwestern University used nurse navigators to assist in coordinating the multidisciplinary evaluation in a timely fashion. Two navigators were hired to make sure any imaging from outside institutions would be reviewed internally within 3 days of receiving the images, and to efficiently schedule any additional workup that was required. Once surgery scheduling was completed, postoperative appointments with the surgeon, medical oncologist, and radiation oncologist were also scheduled. This allowed the patient to receive the recommended adjuvant therapy within a 120day window. The systemic review and use of nurse navigators allowed timely care from diagnosis through treatment.

Fox Chase Cancer Center redesigned their patient access for new patient intake. In the preimprovement design,

14

october 2014 â&#x20AC;˘ Volume 5, number 5

a nonclinical scheduler transferred patients to a preregistration line to leave messages. Registration was inconsistently completed before the initial visit. In the improved design, a nurse navigator performs the intake and then hands the patient off to real-time registration/insurance verification by nonclinical staff. Nurse navigators are connected with the new patients within 24 hours after a visit request. Preregistration is now consistent prior to the first visit and benefits are verified. Also, with the nurse navigatorâ&#x20AC;&#x2122;s clinical expertise, the patient is scheduled for the appropriate type of appointment. The patient is educated about the visit, as well as informed regarding what to bring with him or her or send before the visit. Education from the navigator allows the patient to understand why this information is important to his or her clinical visit and decision-making. The navigators identify and remove barriers to timely cancer treatment. They also meet the patient in person upon arrival for the consult. The use of navigation has led to a 74% retention rate after the first visit, and the time from call to first appointment has been reduced from 14 to 21 days to 7 days. Future opportunities are being visualized as risk assessment and clinical trials plan to be integrated with the program.

Roswell Park Cancer Institute focused on patient satisfaction and wait times. From their analysis, a Patient and Family Advisory Council was formed to help address patient access and intake concerns. Lack of communication and misunderstanding of the time associated with a new patient visit led to the establishment of a patient navigation program. Using existing resources, the educators in the patient resource center contact each new breast cancer patient before the first visit. The patient is contacted 5 or more times through the primary treatment phase, and the final contact is 2 to 3 months after completion of therapy (early survivorship phase). Patient experience improvement was shown with a 40% decrease in complaints and a 10-point increase in patient satisfaction scores.

Congratulations to each of these programs, as well as others that will be used as a model to improve care and the patient experience. The use of nurse navigation as well as nonclinical navigation will contribute to the future trend of quality reporting and value-based reimbursement. g

AONNonline.org

Think Avastin

Clinically meaningful activity in 4 distinct tumor types1

Confronting a common threat across approved indications Indications

Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

Avastin is indicated for the treatment of glioblastoma as a single agent for adult patients with progressive disease following prior therapy. The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avastin.

Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer in combination with carboplatin and paclitaxel.

Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil– based chemotherapy.

Avastin, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidineoxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastincontaining regimen.

Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.

Boxed WARNINGS

Gastrointestinal (GI) perforation — Serious and sometimes fatal GI perforation occurs at a higher incidence in Avastintreated patients compared to controls — The incidences of GI perforation ranged from 0.3% to 2.4% across clinical studies — Discontinue Avastin in patients with GI perforation Surgery and wound healing complications — The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients — Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed. The appropriate interval between termination of Avastin and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined — Discontinue Avastin at least 28 days prior to elective surgery and in patients with wound healing complications requiring medical intervention Hemorrhage — Severe or fatal hemorrhage, including hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving Avastin. Across indications, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 1.2% to 4.6% — Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis (≥1/2 tsp of red blood) — Discontinue Avastin in patients with serious hemorrhage (ie, requiring medical intervention)

Additional serious adverse events

Additional serious and sometimes fatal adverse events with increased incidence in the Avastin-treated arm vs control included — Non-GI fistula formation (≤0.3%) — Arterial thromboembolic events (grade ≥3, 2.6%) — Proteinuria (nephrotic syndrome, <1%) Additional serious adverse events with increased incidence in the Avastin-treated arm vs control included — Hypertension (grade 3–4, 5%–18%) — Reversible posterior leukoencephalopathy syndrome (RPLS) (<0.1%) Infusion reactions with the first dose of Avastin were uncommon (<3%), and severe reactions occurred in 0.2% of patients Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin

Most common adverse events

Across indications, the most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate were — Epistaxis — Rhinitis — Dry skin — Back pain — Headache — Proteinuria — Rectal hemorrhage — Exfoliative dermatitis — Hypertension — Taste alteration — Lacrimation disorder

Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions

Pregnancy warning

Avastin may impair fertility Based on animal data, Avastin may cause fetal harm Advise patients of the potential risk to the fetus during and following Avastin and the need to continue adequate contraception for at least 6 months following the last dose of Avastin For nursing mothers, discontinue nursing or Avastin, taking into account the importance of Avastin to the mother

Indication-specific adverse events

In mRCC, the most common grade 3–5 adverse events in AVOREN, occurring at a ≥2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%), and hemorrhage (3% vs 0.3%) In GBM Study AVF3708g, in patients receiving Avastin alone, the most frequently reported adverse events were infection (55%), fatigue (45%), headache (37%), hypertension (30%), epistaxis (19%), and diarrhea (21%). Of these, the incidence of grade ≥3 adverse events was infection (10%), fatigue (4%), headache (4%), hypertension (8%), and diarrhea (1%). Two deaths were possibly related to Avastin: 1 retroperitoneal hemorrhage and 1 neutropenic infection In GBM patients receiving Avastin alone or Avastin plus irinotecan,* the incidences of Avastin-related adverse events (grade 1–4) were bleeding/hemorrhage (40%), epistaxis (26%), CNS hemorrhage (5%), hypertension (32%), venous thromboembolic events (8%), arterial thromboembolic events (6%), wound healing complications (6%), proteinuria (4%), GI perforation (2%), and RPLS (1%). The incidences of grade 3–5 events in these 163 patients were bleeding/hemorrhage (2%), CNS hemorrhage (1%), hypertension (5%), venous thromboembolic events (7%), arterial thromboembolic events (3%), wound healing complications (3%), proteinuria (1%), and GI perforation (2%). Intracranial hemorrhage occurred in 8 of 163 patients; 2 patients had grade 3–4 hemorrhage In NSCLC, grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events in Study E4599 occurring at a ≥2% higher incidence in Avastin-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thrombus/embolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%) In first-line MCRC, the most common grade 3–4 events in Study 2107, which occurred at a ≥2% higher incidence in the Avastin plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%) In second-line MCRC, the most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (≥2%) in the Avastin plus FOLFOX4 vs FOLFOX4 groups, were diarrhea (18% vs 13%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), ileus (4% vs 1%), neuropathy–sensory (17% vs 9%), neurologic–other (5% vs 3%), fatigue (19% vs 13%), abdominal pain (8% vs 5%), headache (3% vs 0%), hypertension (9% vs 2%), and hemorrhage (5% vs 1%). These data are likely to underestimate the true adverse event rates due to the reporting mechanisms used in this study When continued beyond first progression in MCRC, no new safety signals were observed in the TML study (ML18147) when Avastin was administered in second-line MCRC patients who progressed on an Avastin containing regimen in first-line MCRC. The safety data was consistent with the known safety profile established in first- and second-line MCRC *Avastin is not approved for use in combination with irinotecan or any other combination regimens.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.

You may also report side effects to Genentech at (888) 835-2555.

Please see accompanying brief summary of Prescribing Information, including Boxed WARNINGS, for additional important safety information.

Reference: 1. Avastin Prescribing Information.

Genentech, Inc. March 2013.

©2013 Genentech USA, Inc. All rights reserved. AVA0000488304 Printed in USA. (12/13)

www.avastin-hcp.com

AVASTIN® (bevacizumab)

AVASTIN® (bevacizumab)

AVASTIN® (bevacizumab)

Solution for intravenous infusion Initial U.S. Approval: 2004 This is a brief summary of information about AVASTIN. Before prescribing, please see full Prescribing Information.

gastrointestinal bleeding, hematemesis, CNS hemorrhage, epistaxis, and vaginal bleeding occurred up to five‑fold more frequently in patients receiving Avastin compared to patients receiving only chemotherapy.

Across indications, the incidence of Grade ≥ 3 hemorrhagic events among patients receiving Avastin ranged from 1.2 to 4.6%. [See Adverse Reactions (6.1).]

Serious or fatal pulmonary hemorrhage occurred in four of 13 (31%) patients with squamous cell histology and two of 53 (4%) patients with non‑squamous non‑small cell lung cancer receiving Avastin and chemotherapy compared to none of the 32 (0%) patients receiving chemotherapy alone.

In clinical studies in non–small cell lung cancer where patients with CNS metastases who completed radiation and surgery more than 4 weeks prior to the start of Avastin were evaluated with serial CNS imaging, symptomatic Grade 2 CNS hemorrhage was documented in one of 83 Avastin‑treated patients (rate 1.2%, 95% CI 0.06%–5.93%).

Intracranial hemorrhage occurred in 8 of 163 patients with previously treated glioblastoma; two patients had Grade 3–4 hemorrhage.

Do not administer Avastin to patients with recent history of hemoptysis of ≥ 1/2 teaspoon of red blood. Discontinue Avastin in patients with hemorrhage. [See Boxed Warning, Dosage and Administration (2.4).]

use for which Avastin is not approved. Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin. [See Adverse Reactions (6.1), Use in Specific Populations (8.6).]

WARNING: GASTROINTESTINAL PERFORATIONS, SURGERY AND WOUND HEALING COMPLICATIONS, and HEMORRHAGE Gastrointestinal Perforations The incidence of gastrointestinal perforation, some fatal, in Avastin‑treated patients ranges from 0.3 to 2.4%. Discontinue Avastin in patients with gastrointestinal perforation. [See Dosage and Administration (2.4), Warnings and Precautions (5.1).]

Surgery and Wound Healing Complications The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin‑treated patients. Discontinue Avastin in patients with wound dehiscence. The appropriate interval between termination of Avastin and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined. Discontinue at least 28 days prior to elective surgery. Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed. [See Dosage and Administration (2.4), Warnings and Precautions (5.2), Adverse Reactions (6.1).]

Hemorrhage Severe or fatal hemorrhage, including hemoptysis, gastrointestinal bleeding, central nervous systems (CNS) hemorrhage, epistaxis, and vaginal bleeding occurred up to five‑fold more frequently in patients receiving Avastin. Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis. [See Dosage and Administration (2.4), Warnings and Precautions (5.3), Adverse Reactions (6.1).]

1.3 Glioblastoma Avastin is indicated for the treatment of glioblastoma with progressive disease in adult patients following prior therapy as a single agent.

The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease‑related symptoms or increased survival with Avastin. [See Clinical Studies (14.4).]

1.4 Metastatic Renal Cell Carcinoma (mRCC) Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

4 CONTRAINDICATIONS None.

5 WARNINGS AND PRECAUTIONS 5.1 Gastrointestinal Perforations Serious and sometimes fatal gastrointestinal perforation occurs at a higher incidence in Avastin treated patients compared to controls. The incidence of gastrointestinal perforation ranged from 0.3 to 2.4% across clinical studies. [See Adverse Reactions (6.1).]

The typical presentation may include abdominal pain, nausea, emesis, constipation, and fever. Perforation can be complicated by intra‑abdominal abscess and fistula formation. The majority of cases occurred within the first 50 days of initiation of Avastin.

Discontinue Avastin in patients with gastrointestinal perforation. [See Boxed Warning, Dosage and Administration (2.4).]

5.2 Surgery and Wound Healing Complications Avastin impairs wound healing in animal models. [See Nonclinical Toxicology (13.2).] In clinical trials, administration of Avastin was not allowed until at least 28 days after surgery. In a controlled clinical trial, the incidence of wound healing complications, including serious and fatal complications, in patients with mCRC who underwent surgery during the course of Avastin treatment was 15% and in patients who did not receive Avastin, was 4%. [See Adverse Reactions (6.1).]

Avastin should not be initiated for at least 28 days following surgery and until the surgical wound is fully healed. Discontinue Avastin in patients with wound healing complications requiring medical intervention.

The appropriate interval between the last dose of Avastin and elective surgery is unknown; however, the half‑life of Avastin is estimated to be 20 days. Suspend Avastin for at least 28 days prior to elective surgery. Do not administer Avastin until the wound is fully healed. [See Boxed Warning, Dosage and Administration (2.4).]

Necrotizing fasciitis including fatal cases, has been reported in patients treated with Avastin; usually secondary to wound healing complications, gastrointestinal perforation or fistula formation. Discontinue Avastin therapy in patients who develop necrotizing fasciitis. [See Adverse Reactions (6.3).]

5.3 Hemorrhage Avastin can result in two distinct patterns of bleeding: minor hemorrhage, most commonly Grade 1 epistaxis; and serious, and in some cases fatal, hemorrhagic events. Severe or fatal hemorrhage, including hemoptysis,

5.5 Arterial Thromboembolic Events Serious, sometimes fatal, arterial thromboembolic events (ATE) including cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and a variety of other ATE occurred at a higher incidence in patients receiving Avastin compared to those in the control arm. Across indications, the incidence of Grade ≥ 3 ATE in the Avastin containing arms was 2.6% compared to 0.8% in the control arms. Among patients receiving Avastin in combination with chemotherapy, the risk of developing ATE during therapy was increased in patients with a history of arterial thromboembolism, diabetes, or age greater than 65 years. [See Use in Specific Populations (8.5).]

The safety of resumption of Avastin therapy after resolution of an ATE has not been studied. Discontinue Avastin in patients who experience a severe ATE. [See Dosage and Administration (2.4).]

5.6 Hypertension The incidence of severe hypertension is increased in patients receiving Avastin as compared to controls. Across clinical studies the incidence of Grade 3 or 4 hypertension ranged from 5‑18%.

Monitor blood pressure every two to three weeks during treatment with Avastin. Treat with appropriate anti‑hypertensive therapy and monitor blood pressure regularly. Continue to monitor blood pressure at regular intervals in patients with Avastin‑induced or ‑exacerbated hypertension after discontinuation of Avastin.

Temporarily suspend Avastin in patients with severe hypertension that is not controlled with medical management. Discontinue Avastin in patients with hypertensive crisis or hypertensive encephalopathy. [See Dosage and Administration (2.4).]

5.7 Reversible Posterior Leukoencephalopathy Syndrome (RPLS) RPLS has been reported with an incidence of < 0.1% in clinical studies. The onset of symptoms occurred from 16 hours to 1 year after initiation of Avastin. RPLS is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances. Mild to severe hypertension may be present. Magnetic resonance imaging (MRI) is necessary to confirm the diagnosis of RPLS. Discontinue Avastin in patients developing RPLS. Symptoms usually resolve or improve within days, although some patients have experienced ongoing neurologic sequelae. The safety of reinitiating Avastin therapy in patients previously experiencing RPLS is not known. [See Dosage and Administration (2.4).]

5.8 Proteinuria The incidence and severity of proteinuria is increased in patients receiving Avastin as compared to controls. Nephrotic syndrome occurred in < 1% of patients receiving Avastin in clinical trials, in some instances with fatal outcome. [See Adverse Reactions (6.1).] In a published case series, kidney biopsy of six patients with proteinuria showed findings consistent with thrombotic microangiopathy.

Monitor proteinuria by dipstick urine analysis for the development or worsening of proteinuria with serial urinalyses during Avastin therapy.

Patients with a 2 + or greater urine dipstick reading should undergo further assessment with a 24‑hour urine collection.

Suspend Avastin administration for ≥ 2 grams of proteinuria/24 hours and resume when proteinuria is < 2 gm/24 hours. Discontinue Avastin in patients with nephrotic syndrome. [See Dosage and Administration (2.4).]

Data from a postmarketing safety study showed poor correlation between UPCR (Urine Protein/Creatinine Ratio) and 24 hour urine protein (Pearson Correlation 0.39 (95% CI 0.17, 0.57). [See Use in Specific Populations (8.5).]

5.9 Infusion Reactions Infusion reactions reported in the clinical trials and post‑marketing experience include hypertension, hypertensive crises associated with neurologic signs and symptoms, wheezing, oxygen desaturation, Grade 3 hypersensitivity, chest pain, headaches, rigors, and diaphoresis. In clinical studies, infusion reactions with the first dose of Avastin were uncommon (< 3%) and severe reactions occurred in 0.2% of patients.

Stop infusion if a severe infusion reaction occurs and administer appropriate medical therapy. [See Dosage and Administration (2.4).]

5.10 Ovarian Failure The incidence of ovarian failure was higher (34% vs. 2%) in premenopausal women receiving Avastin in combination with mFOLFOX chemotherapy as compared to those receiving mFOLFOX chemotherapy alone for adjuvant treatment for colorectal cancer, a

6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data below reflect exposure to Avastin in 4599 patients with CRC, non‑squamous NSCLC, glioblastoma, or mRCC trials including controlled (Studies 1, 2, 4, 5 and 8) or uncontrolled, single arm (Study 6) treated at the recommended dose and schedule for a median of 8 to 23 doses of Avastin.

[See Clinical Studies (14).] The population was aged 18‑89 years (median 60 years), 45.4% male and 85.8% (3729/4345) White. The population included 2184 first‑ and second‑line mCRC patients who received a median of 10 doses of Avastin, 480 first‑line metastatic NSCLC patients who received a median of 8 doses of Avastin, 163 glioblastoma patients who received a median of 9 doses of Avastin, and 337 mRCC patients who received a median of 16 doses of Avastin. These data also reflect exposure to Avastin in 363 patients with metastatic breast cancer (MBC) who received a median of 9.5 doses of Avastin, 669 female adjuvant CRC patients who received a median of 23 doses of Avastin and exposure to Avastin in 403 previously untreated patients with diffuse large B‑cell lymphoma (DLBCL) who received a median of 8 doses of Avastin. Avastin is not approved for use in MBC, adjuvant CRC, or DLBCL. Surgery and Wound Healing Complications The incidence of post‑operative wound healing and/or bleeding complications was increased in patients with mCRC receiving Avastin as compared to patients receiving only chemotherapy. Among patients requiring surgery on or within 60 days of receiving study treatment, wound healing and/or bleeding complications occurred in 15% (6/39) of patients receiving bolus‑IFL plus Avastin as compared to 4% (1/25) of patients who received bolus‑IFL alone.

In Study 6, events of post‑operative wound healing complications (craniotomy site wound dehiscence and cerebrospinal fluid leak) occurred in patients with previously treated glioblastoma: 3/84 patients in the Avastin alone arm and 1/79 patients in the Avastin plus irinotecan arm. [See Boxed Warning, Dosage and Administration (2.4), Warnings and Precautions (5.2).]

Hemorrhage The incidence of epistaxis was higher (35% vs. 10%) in patients with mCRC receiving bolus‑IFL plus Avastin compared with patients receiving bolus‑IFL plus placebo. All but one of these events were Grade 1 in severity and resolved without medical intervention. Grade 1 or 2 hemorrhagic events were more frequent in patients receiving bolus‑IFL plus Avastin when compared to those receiving bolus‑IFL plus placebo and included gastrointestinal hemorrhage (24% vs. 6%), minor gum bleeding (2% vs. 0), and vaginal hemorrhage (4% vs. 2%). [See Boxed Warning, Dosage and Administration (2.4), Warnings and Precautions (5.3).]

Venous Thromboembolic Events The overall incidence of Grade 3–4 venous thromboembolic events in Study 1 was 15.1% in patients receiving bolus‑IFL plus Avastin and 13.6% in patients receiving bolus‑IFL plus placebo. In Study 1, more patients in the Avastin containing arm experienced deep venous thrombosis (34 vs. 19 patients ) and intra‑abdominal venous thrombosis (10 vs. 5 patients).

The risk of developing a second thromboembolic event while on Avastin and oral anticoagulants was evaluated in two randomized studies. In Study 1, 53 patients (14%) on the bolus‑IFL plus Avastin arm and 30 patients (8%) on the bolus‑IFL plus placebo arm received full dose warfarin following a venous thromboembolic event (VTE). Among these patients, an additional thromboembolic event occurred in 21% (11/53) of patients receiving bolus‑IFL plus Avastin and 3% (1/30) of patients receiving bolus‑IFL alone.

In a second, randomized, 4‑arm study in 1401 patients with mCRC, prospectively evaluating the incidence of VTE (all grades), the overall incidence of first VTE was higher in the Avastin containing arms (13.5%) than the chemotherapy alone arms (9.6%). Among the 116 patients treated with anticoagulants following an initial VTE event (73 in the Avastin plus chemotherapy arms and 43 in the chemotherapy alone arms), the overall incidence of subsequent VTEs was also higher among the Avastin treated patients (31.5% vs. 25.6%). In this subgroup of patients treated with anticoagulants, the overall incidence of bleeding, the majority of which were Grade 1, was higher in the Avastin treated arms than the chemotherapy arms (27.4% vs. 20.9%). [See Dosage and Administration (2.4).]

Safety:10”

1 INDICATIONS AND USAGE 1.1 Metastatic Colorectal Cancer (mCRC) Avastin is indicated for the first‑ or second‑line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5‑fluorouracil–based chemotherapy.

Avastin, in combination with fluoropyrimidine‑irinotecan‑ or fluoropyrimidine‑oxaliplatin‑based chemotherapy, is indicated for the second‑line treatment of patients with metastatic colorectal cancer who have progressed on a first‑line Avastin‑containing regimen.

Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer. [See Clinical Studies (14.2).]

1.2 Non‑Squamous Non–Small Cell Lung Cancer (NSCLC) Avastin is indicated for the first‑line treatment of unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer in combination with carboplatin and paclitaxel.

5.4 Non‑Gastrointestinal Fistula Formation Serious and sometimes fatal non‑gastrointestinal fistula formation involving tracheo‑esophageal, bronchopleural, biliary, vaginal, renal and bladder sites occurs at a higher incidence in Avastin‑treated patients compared to controls. The incidence of non‑gastrointestinal perforation was ≤ 0.3% in clinical studies. Most events occurred within the first 6 months of Avastin therapy.

Discontinue Avastin in patients with fistula formation involving an internal organ. [See Dosage and Administration (2.4).]

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label: • Gastrointestinal Perforations [See Boxed Warning, Dosage and Administration (2.4), Warnings and Precautions (5.1).]

• Surgery and Wound Healing Complications [See Boxed Warning, Dosage and Administration (2.4), Warnings and Precautions (5.2).]

• Hemorrhage [See Boxed Warning, Dosage and Administration (2.4), Warnings and Precautions (5.3).]

• Non‑Gastrointestinal Fistula Formation [See Dosage and Administration (2.4), Warnings and Precautions (5.4).]

• Arterial Thromboembolic Events [See Dosage and Administration (2.4), Warnings and Precautions (5.5).]

• Hypertensive Crisis [See Dosage and Administration (2.4), Warnings and Precautions (5.6).]

• Reversible Posterior Leukoencephalopathy Syndrome [See Dosage and Administration (2.4), Warnings and Precautions (5.7).]

• Proteinuria [See Dosage and Administration (2.4), Warnings and Precautions (5.8).]

• Ovarian Failure [See Warnings and Precautions (5.10), Use in Specific Populations (8.6).]

The most common adverse reactions observed in Avastin patients at a rate > 10% and at least twice the control arm rate, are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain and exfoliative dermatitis.

Across all studies, Avastin was discontinued in 8.4 to 21% of patients because of adverse reactions.

AVASTIN® (bevacizumab)

AVASTIN® (bevacizumab)

AVASTIN® (bevacizumab)

Neutropenia and Infection The incidences of neutropenia and febrile neutropenia are increased in patients receiving Avastin plus chemotherapy compared to chemotherapy alone. In Study 1, the incidence of Grade 3 or 4 neutropenia was increased in mCRC patients receiving IFL plus Avastin (21%) compared to patients receiving IFL alone (14%). In Study 5, the incidence of Grade 4 neutropenia was increased in NSCLC patients receiving paclitaxel/carboplatin (PC) plus Avastin (26.2%) compared with patients receiving PC alone (17.2%). Febrile neutropenia was also increased (5.4% for PC plus Avastin vs.

1.8% for PC alone). There were 19 (4.5%) infections with Grade 3 or 4 neutropenia in the PC plus Avastin arm of which 3 were fatal compared to 9 (2%) neutropenic infections in patients receiving PC alone, of which none were fatal. During the first 6 cycles of treatment, the incidence of serious infections including pneumonia, febrile neutropenia, catheter infections and wound infections was increased in the PC plus Avastin arm [58 patients (13.6%)] compared to the PC alone arm [29 patients (6.6%)].

In Study 6, one fatal event of neutropenic infection occurred in a patient with previously treated glioblastoma receiving Avastin alone. The incidence of any grade of infection in patients receiving Avastin alone was 55% and the incidence of Grade 3–5 infection was 10%.

Grade 1–4 adverse events which occurred at a higher incidence (≥ 5%) in patients receiving bolus‑IFL plus Avastin as compared to the bolus‑IFL plus placebo arm are presented in Table 2. Grade 1–4 adverse events were collected for the first approximately 100 patients in each of the three treatment arms who were enrolled until enrollment in Arm 3 (5‑FU/LV + Avastin) was discontinued.

Table 2 NCI‑CTC Grade 1‑4 Adverse Events in Study 1 (Occurring at Higher Incidence [≥ 5%] in IFL + Avastin vs. IFL)

small intestinal hemorrhage, aneurysm ruptured, gastric ulcer hemorrhage, gingival bleeding, haemoptysis, hemorrhage intracranial, large intestinal hemorrhage, respiratory tract hemorrhage, and traumatic hematoma).

Grade 1–5 adverse events occurring at a higher incidence ( ≥ 5%) in patients receiving IFN‑α plus Avastin compared to the IFN‑α plus placebo arm are presented in Table 3.

Table 3 NCI‑CTC Grades 1−5 Adverse Events in Study 8 (Occurring at Higher Incidence [≥5%] in IFN‑α + Avastin vs. IFN‑α + Placebo)

Proteinuria Grade 3–4 proteinuria ranged from 0.7 to 7.4% in Studies 1, 2, 4, 5 and 8. The overall incidence of proteinuria (all grades) was only adequately assessed in Study 8, in which the incidence was 20%. Median onset of proteinuria was 5.6 months (range 15 days to 37 months) after initiation of Avastin. Median time to resolution was 6.1 months (95% CI 2.8 months, 11.3 months). Proteinuria did not resolve in 40% of patients after median follow up of 11.2 months and required permanent discontinuation of Avastin in 30% of the patients who developed proteinuria (Study 8).

In an exploratory, pooled analysis of 8,273 patients treated in 7 randomized clinical trials, 5.4% (271 of 5037) of patients receiving Avastin in combination with chemotherapy experienced Grade ≥ 2 proteinuria. The Grade ≥ 2 proteinuria resolved in 74.2% (201 of 271) of patients. Avastin was re‑initiated in 41.7% (113 of 271) of patients. Of the 113 patients who re‑initiated Avastin, 47.8% (54 of 113) experienced a second episode of Grade ≥ 2 proteinuria. [See Warnings and Precautions (5.8).]

Ovarian Failure The incidence of new cases of ovarian failure (defined as amenorrhoea lasting 3 or more months, FSH level ≥ 30 mIU/mL and a negative serum β‑HCG pregnancy test) was prospectively evaluated in a subset of 179 women receiving mFOLFOX chemotherapy alone (n = 84) or with Avastin (n = 95). New cases of ovarian failure were identified in 34% (32/95) of women receiving Avastin in combination with chemotherapy compared with 2% (2/84) of women receiving chemotherapy alone [relative risk of 14 (95% CI 4, 53)]. After discontinuation of Avastin treatment, recovery of ovarian function at all time points during the post‑treatment period was demonstrated in 22% (7/32) of the Avastin‑treated women. Recovery of ovarian function is defined as resumption of menses, a positive serum β‑HCG pregnancy test, or a FSH level < 30 mIU/mL during the post‑treatment period. Long term effects of Avastin exposure on fertility are unknown. [See Warnings and Precautions (5.10), Use in Specific Populations (8.6).]

Metastatic Colorectal Cancer (mCRC) The data in Table 1 and Table 2 were obtained in Study 1, a randomized, double‑blind, controlled trial comparing chemotherapy plus Avastin with chemotherapy plus placebo. Avastin was administered at 5 mg/kg every 2 weeks.

All Grade 3–4 adverse events and selected Grade 1–2 adverse events (hypertension, proteinuria, thromboembolic events) were collected in the entire study population. Severe and life‑threatening (Grade 3–4) adverse events, which occurred at a higher incidence ( ≥ 2%) in patients receiving bolus‑IFL plus Avastin as compared to bolus‑IFL plus placebo, are presented in Table 1.

Table 1 NCI‑CTC Grade 3−4 Adverse Events in Study 1 (Occurring at Higher Incidence [ ≥ 2 %] Avastin vs. Control)

NCI‑CTC Grade 3‑4 Events Body as a Whole Asthenia Abdominal Pain Pain Cardiovascular Hypertension Deep Vein Thrombosis Intra‑Abdominal Thrombosis Syncope Digestive Diarrhea Constipation Hemic/Lymphatic Leukopenia Neutropeniaa a

Arm 1 IFL+ + Placebo (n = 396) 74%

Arm 2 IFL+ + Avastin (n = 392) 87%

7% 5% 5%

10% 8% 8%

2% 5% 1% 1%

12% 9% 3% 3%

25% 2%

34% 4%

31% 14%

37% 21%

Central laboratories were collected on Days 1 and 21 of each cycle.

Neutrophil counts are available in 303 patients in Arm 1 and 276 in Arm 2.

Body as a Whole Pain Abdominal Pain Headache Cardiovascular Hypertension Hypotension Deep Vein Thrombosis Digestive Vomiting Anorexia Constipation Stomatitis Dyspepsia GI Hemorrhage Weight Loss Dry Mouth Colitis Hemic/Lymphatic Thrombocytopenia Nervous Dizziness Respiratory Upper Respiratory Infection Epistaxis Dyspnea Voice Alteration Skin/Appendages Alopecia Skin Ulcer Special Senses Taste Disorder Urogenital Proteinuria

55% 55% 19%

61% 61% 26%

62% 50% 26%

14% 7% 3%

23% 15% 9%

34% 7% 6%

47% 30% 29% 18% 15% 6% 10% 2% 1%

52% 43% 40% 32% 24% 24% 15% 7% 6%

47% 35% 29% 30% 17% 19% 16% 4% 1%

0%

5%

5%

20%

26%

19%

39% 10% 15% 2%

47% 35% 26% 9%

40% 32% 25% 6%

26% 1%

32% 6%

6% 6%

9%

14%

21%

24%

36%

36%

Avastin in Combination with FOLFOX4 in Second‑line mCRC Only Grade 3‑5 non‑hematologic and Grade 4–5 hematologic adverse events related to treatment were collected in Study 2. The most frequent adverse events (selected Grade 3–5 non‑hematologic and Grade 4–5 hematologic adverse events) occurring at a higher incidence (≥2%) in 287 patients receiving FOLFOX4 plus Avastin compared to 285 patients receiving FOLFOX4 alone were fatigue (19% vs. 13%), diarrhea (18% vs.

13%), sensory neuropathy (17% vs. 9%), nausea (12% vs. 5%), vomiting (11% vs. 4%), dehydration (10% vs. 5%), hypertension (9% vs. 2%), abdominal pain (8% vs. 5%), hemorrhage (5% vs. 1%), other neurological (5% vs. 3%), ileus (4% vs. 1%) and headache (3% vs. 0%). These data are likely to under‑estimate the true adverse event rates due to the reporting mechanisms used in Study 2.

Avastin in Combination with Fluoropyrimidine‑Irinotecan or Fluoropyrimidine‑ Oxaliplatin Based Chemotherapy in Second‑line mCRC Patients who have Progressed on an Avastin Containing Regimen in First‑line mCRC: No new safety signals were observed in Study 4 when Avastin was administered in second line mCRC patients who progressed on an Avastin containing regimen in first line mCRC. The safety data was consistent with the known safety profile established in first and second line mCRC. Unresectable Non‑Squamous Non‑Small Cell Lung Cancer (NSCLC) Only Grade 3‑5 non‑hematologic and Grade 4‑5 hematologic adverse events were collected in Study 5. Grade 3–5 non‑hematologic and Grade 4–5 hematologic adverse events (occurring at a higher incidence (≥2%) in 427 patients receiving PC plus Avastin compared with 441 patients receiving PC alone were neutropenia (27% vs. 17%), fatigue (16% vs. 13%), hypertension (8% vs. 0.7%), infection without neutropenia (7% vs. 3%), venous thrombus/embolism (5% vs. 3%), febrile neutropenia (5% vs. 2%), pneumonitis/ pulmonary infiltrates (5% vs. 3%), infection with Grade 3 or 4 neutropenia (4% vs. 2%), hyponatremia (4% vs. 1%), headache (3% vs. 1%) and proteinuria (3% vs. 0%).

Glioblastoma All adverse events were collected in 163 patients enrolled in Study 6 who either received Avastin alone or Avastin plus irinotecan. All patients received prior radiotherapy and temozolomide. Avastin was administered at 10 mg/kg every 2 weeks alone or in combination with irinotecan. Avastin was discontinued due to adverse events in 4.8% of patients treated with Avastin alone.

In patients receiving Avastin alone (N = 84), the most frequently reported adverse events of any grade were infection (55%), fatigue (45%), headache (37%), hypertension (30%), epistaxis (19%) and diarrhea (21%). Of these, the incidence of Grade ≥ 3 adverse events was infection (10%), fatigue (4%), headache (4%), hypertension (8%) and diarrhea (1%). Two deaths on study were possibly related to Avastin: one retroperitoneal hemorrhage and one neutropenic infection.

In patients receiving Avastin alone or Avastin plus irinotecan (N = 163), the incidence of Avastin‑related adverse events (Grade 1–4) were bleeding/ hemorrhage (40%), epistaxis (26%), CNS hemorrhage (5%), hypertension (32%), venous thromboembolic event (8%), arterial thromboembolic event (6%), wound‑healing complications (6%), proteinuria (4%), gastrointestinal perforation (2%), and RPLS (1%). The incidence of Grade 3–5 events in these 163 patients were bleeding/hemorrhage (2%), CNS hemorrhage (1%), hypertension (5%), venous thromboembolic event (7%), arterial thromboembolic event (3%), wound‑healing complications (3%), proteinuria (1%), and gastrointestinal perforation (2%).

Metastatic Renal Cell Carcinoma (mRCC) All grade adverse events were collected in Study 8. Grade 3–5 adverse events occurring at a higher incidence (≥ 2%) in 337 patients receiving interferon alfa (IFN‑α) plus Avastin compared to 304 patients receiving IFN‑α plus placebo arm were fatigue (13% vs. 8%), asthenia (10% vs. 7%), proteinuria (7% vs. 0%), hypertension (6% vs. 1%; including hypertension and hypertensive crisis), and hemorrhage (3% vs. 0.3%; including epistaxis,

System Organ Class/ IFN‑α + Placebo (n = 304) Preferred terma Gastrointestinal disorders Diarrhea 16% General disorders and administration site conditions Fatigue 27% Investigations Weight decreased 15% Metabolism and nutrition disorders Anorexia 31% Musculoskeletal and connective tissue disorders Myalgia 14% Back pain 6% Nervous system disorders Headache 16% Renal and urinary disorders Proteinuria 3% Respiratory, thoracic and mediastinal disorders Epistaxis 4% Dysphonia 0% Vascular disorders Hypertension 9% a

IFN‑α + Avastin (n = 337) 21% 33% 20% 36% 19% 12% 24% 20% 27% 5% 28%

Adverse events were encoded using MedDRA, Version 10.1.

The following adverse events were reported at a 5‑fold greater incidence in the IFN‑α plus Avastin arm compared to IFN‑α alone and not represented in Table 3: gingival bleeding (13 patients vs. 1 patient); rhinitis (9 vs. 0); blurred vision (8 vs. 0); gingivitis (8 vs. 1); gastroesophageal reflux disease (8 vs. 1); tinnitus (7 vs. 1); tooth abscess (7 vs. 0); mouth ulceration (6 vs. 0); acne (5 vs. 0); deafness (5 vs. 0); gastritis (5 vs. 0); gingival pain (5 vs. 0) and pulmonary embolism (5 vs. 1).

6.2 Immunogenicity As with all therapeutic proteins, there is a potential for an immune response to Avastin. In clinical trials of adjuvant colon carcinoma, 14 of 2233 evaluable patients (0.63%) tested positive for treatment‑emergent anti‑bevacizumab antibodies detected by an electrochemiluminescent (ECL) based assay. Among these 14 patients, three tested positive for neutralizing antibodies against bevacizumab using an enzyme‑linked immunosorbent assay (ELISA). The clinical significance of these anti‑product antibody responses to bevacizumab is unknown.

Immunogenicity assay results are highly dependent on the sensitivity and specificity of the test method and may be influenced by several factors, including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Avastin with the incidence of antibodies to other products may be misleading.

6.3 Postmarketing Experience The following adverse reactions have been identified during post‑approval use of Avastin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: Polyserositis Cardiovascular: Pulmonary hypertension, RPLS, Mesenteric venous occlusion Eye disorders (from unapproved intravitreal use for treatment of various ocular disorders): Permanent loss of vision; Endophthalmitis (infectious and sterile); Intraocular inflammation; Retinal detachment; Increased intraocular pressure; Hemorrhage including conjunctival, vitreous hemorrhage or retinal hemorrhage; Vitreous floaters; Ocular hyperemia; Ocular pain or discomfort Gastrointestinal: Gastrointestinal ulcer, Intestinal necrosis, Anastomotic ulceration Hemic and lymphatic: Pancytopenia Hepatobiliary disorders: Gallbladder perforation Infections and infestations: Necrotizing fasciitis, usually secondary to wound healing complications, gastrointestinal perforation or fistula formation Musculoskeletal: Osteonecrosis of the jaw Renal: Renal thrombotic microangiopathy (manifested as severe proteinuria) Respiratory: Nasal septum perforation, dysphonia Systemic Events (from unapproved intravitreal use for treatment of various ocular disorders): Arterial thromboembolic events, Hypertension, Gastrointestinal perforation, Hemorrhage 7 DRUG INTERACTIONS A drug interaction study was performed in which irinotecan was administered as part of the FOLFIRI regimen with or without Avastin. The results demonstrated no significant effect of bevacizumab on the pharmacokinetics of irinotecan or its active metabolite SN38.

In a randomized study in 99 patients with NSCLC, based on limited data, there did not appear to be a difference in the mean exposure of either carboplatin or paclitaxel when each was administered alone or in combination with Avastin.

However, 3 of the 8 patients receiving Avastin plus paclitaxel/carboplatin had substantially lower paclitaxel exposure after four cycles of treatment (at Day 63) than those at Day 0, while patients receiving paclitaxel/carboplatin without Avastin had a greater paclitaxel exposure at Day 63 than at Day 0.

In Study 8, there was no difference in the mean exposure of interferon alfa administered in combination with Avastin when compared to interferon alfa alone.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C There are no adequate or well controlled studies of bevacizumab in pregnant women.

While it is not known if bevacizumab crosses the placenta, human IgG is known to cross the placenta. Reproduction studies in rabbits treated with approximately

Safety:10”

T:10.75”

Congestive Heart Failure (CHF) The incidence of Grade ≥ 3 left ventricular dysfunction was 1.0% in patients receiving Avastin compared to 0.6% in the control arm across indications. In patients with metastatic breast cancer (MBC), an indication for which Avastin is not approved, the incidence of Grade 3–4 CHF was increased in patients in the Avastin plus paclitaxel arm (2.2%) as compared to the control arm (0.3%). Among patients receiving prior anthracyclines for MBC, the rate of CHF was 3.8% for patients receiving Avastin as compared to 0.6% for patients receiving paclitaxel alone.

The safety of continuation or resumption of Avastin in patients with cardiac dysfunction has not been studied.

In previously untreated patients with diffuse large B‑cell lymphoma (DLBCL), an indication for which Avastin is not approved, the incidence of CHF and decline in left‑ventricular ejection fraction (LVEF) were significantly increased in the Avastin plus R‑CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) arm (n=403) compared to the placebo plus R‑CHOP arm (n=379); both regimens were given for 6 to 8 cycles. At the completion of R‑CHOP therapy, the incidence of CHF was 10.9% in the Avastin plus R‑CHOP arm compared to 5.0% in the R‑CHOP alone arm [relative risk (95% CI) of 2.2 (1.3, 3.7)]. The incidence of a LVEF event, defined as a decline from baseline of 20% or more in LVEF or a decline from baseline of 10% or more to a LVEF value of less than 50%, was also increased in the Avastin plus R‑CHOP arm (10.4%) compared to the R‑CHOP alone arm (5.0%). Time to onset of left‑ventricular dysfunction or CHF was 1‑6 months after initiation of therapy in at least 85% of the patients and was resolved in 62% of the patients experiencing CHF in the Avastin arm compared to 82% in the control arm.

Arm 1 Arm 2 Arm 3 IFL + Placebo IFL + Avastin 5‑FU/LV + Avastin (n = 98) (n = 102) (n = 109)

Safety:2.6875" AVASTIN® (bevacizumab) 1 to 12 times the recommended human dose of bevacizumab demonstrated teratogenicity, including an increased incidence of specific gross and skeletal fetal alterations. Adverse fetal outcomes were observed at all doses tested. Other observed effects included decreases in maternal and fetal body weights and an increased number of fetal resorptions. [See Nonclinical Toxicology (13.3).]

Because of the observed teratogenic effects of bevacizumab in animals and of other inhibitors of angiogenesis in humans, bevacizumab should be used during pregnancy only if the potential benefit to the pregnant woman justifies the potential risk to the fetus.

8.3 Nursing Mothers It is not known whether Avastin is secreted in human milk. Human IgG is excreted in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from bevacizumab, a decision should be made whether to discontinue nursing or discontinue drug, taking into account the half‑life of the bevacizumab (approximately 20 days [range 11–50 days]) and the importance of the drug to the mother. [See Clinical Pharmacology (12.3).]

8.4 Pediatric Use The safety, effectiveness and pharmacokinetic profile of Avastin in pediatric patients have not been established.

Antitumor activity was not observed among eight children with relapsed glioblastoma treated with bevacizumab and irinotecan. There is insufficient information to determine the safety and efficacy of Avastin in children with glioblastoma.

Juvenile cynomolgus monkeys with open growth plates exhibited physeal dysplasia following 4 to 26 weeks exposure at 0.4 to 20 times the recommended human dose (based on mg/kg and exposure). The incidence and severity of physeal dysplasia were dose‑related and were partially reversible upon cessation of treatment.

8.5 Geriatric Use In Study 1, severe adverse events that occurred at a higher incidence (≥ 2%) in patients aged ≥65 years as compared to younger patients were asthenia, sepsis, deep thrombophlebitis, hypertension, hypotension, myocardial infarction, congestive heart failure, diarrhea, constipation, anorexia, leukopenia, anemia, dehydration, hypokalemia, and hyponatremia. The effect of Avastin on overall survival was similar in elderly patients as compared to younger patients.

In Study 2, patients aged ≥65 years receiving Avastin plus FOLFOX4 had a greater relative risk as compared to younger patients for the following adverse events: nausea, emesis, ileus, and fatigue.

In Study 5, patients aged ≥65 years receiving carboplatin, paclitaxel, and Avastin had a greater relative risk for proteinuria as compared to younger patients. [See Warnings and Precautions (5.8).]

10 OVERDOSAGE The highest dose tested in humans (20 mg/kg IV) was associated with headache in nine of 16 patients and with severe headache in three of 16 patients.

17 PATIENT COUNSELING INFORMATION Advise patients: • To undergo routine blood pressure monitoring and to contact their health care provider if blood pressure is elevated.

• To immediately contact their health care provider for unusual bleeding, high fever, rigors, sudden onset of worsening neurological function, or persistent or severe abdominal pain, severe constipation, or vomiting.

• Of increased risk of wound healing complications during and following Avastin.

• Of increased risk of an arterial thromboembolic event.

• Of the potential risk to the fetus during and following Avastin and the need to continue adequate contraception for at least 6 months following last dose of Avastin.

• Of the increased risk for ovarian failure following Avastin treatment.

Avastin® (bevacizumab) Manufactured by: Genentech, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080‑4990

03/14 AVA0000764707 Initial U.S. Approval: February 2004 Code Revision Date: March 2014 Avastin® is a registered trademark of Genentech, Inc. © 2014 Genentech, Inc.

T:10.75”

In a prospectively designed substudy of 179 premenopausal women randomized to receive chemotherapy with or without Avastin, the incidence of ovarian failure was higher in the Avastin arm (34%) compared to the control arm (2%). After discontinuation of Avastin and chemotherapy, recovery of ovarian function occurred in 22% (7/32) of these Avastin‑treated patients. [See Warnings and Precautions (5.10), Adverse Reactions (6.1).]

Safety:10”

8.6 Females of Reproductive Potential Avastin increases the risk of ovarian failure and may impair fertility. Inform females of reproductive potential of the risk of ovarian failure prior to starting treatment with Avastin. Long term effects of Avastin exposure on fertility are unknown.

Safety:9.125"

Of the 742 patients enrolled in Genentech‑sponsored clinical studies in which all adverse events were captured, 212 (29%) were age 65 or older and 43 (6%) were age 75 or older. Adverse events of any severity that occurred at a higher incidence in the elderly as compared to younger patients, in addition to those described above, were dyspepsia, gastrointestinal hemorrhage, edema, epistaxis, increased cough, and voice alteration.

In an exploratory, pooled analysis of 1745 patients treated in five randomized, controlled studies, there were 618 (35%) patients aged ≥65 years and 1127 patients <65 years of age. The overall incidence of arterial thromboembolic events was increased in all patients receiving Avastin with chemotherapy as compared to those receiving chemotherapy alone, regardless of age. However, the increase in arterial thromboembolic events incidence was greater in patients aged ≥65 years (8.5% vs. 2.9%) as compared to those <65 years (2.1% vs. 1.4%).

[See Warnings and Precautions (5.5).]

A focus on the Commission on cancer

Development and Evolution of an Oncology Nurse Navigation Program: From Formation to Fruition Peggy Malone, RN, BS, OCN; Lisa Bruno, RN, BSN, OCN; Beth Hayden, RN, BSN, MBA, OCN; Julie Carlson, RN, MSN, APN, AOCNS OSF Saint Anthony Center for Cancer Care

I

n preparation for the new American College of Surgeons Commission on Cancer (CoC) standards,1 OSF Saint Anthony Medical Center focused on having an oncology nurse navigation program in place to support patients by January 2014. The Center for Cancer Care at OSF Saint Anthony Medical Center is a comprehensive cancer center located in an urban setting in the Midwestern United States. The most recent CoC site survey was conducted in September 2011, and the center received accreditation with commendation. The center also received the CoC Outstanding Achievement Award for the 2011 survey. The current volume of patients is approximately 850 analytical new cases per year.

The new CoC standards require that a patient navigation process be in place by 2015. The standards concentrate on individualized assistance for patients with cancer to overcome common barriers encountered in the healthcare system. The standards aim to ensure that patients have access to psychosocial support through distress screening and appropriate referrals. In addition, the standards define requirements for survivorship care planning for patients completing cancer treatments.

Extremely positive anecdotal feedback from a 4-year pilot program using an oncology nurse navigator (ONN) for breast cancer patients prompted the center to pursue the development of an oncology nurse navigation program. In order to build a stronger program, actions were taken to restructure the framework of the program to meet specific patient care needs, to comply with the new CoC standards, and to positively affect outcomes. The center developed a collaborative action plan using a step-by-step framework (Figure 1).

This article will focus on the steps taken to launch and develop an oncology nurse navigation program.

timely care, community resource referrals, and mobilizing financial assistance.2,3 Key stakeholders, including the department director, medical oncologists, and the ONN currently involved in the pilot program, met in a work group format on a monthly basis beginning in 2010. The small work group reviewed the successful components of the program and evaluated ways to implement improvements in the existing pilot oncology nurse navigation program. The following steps were taken: â&#x20AC;˘ A literature review was conducted and resources were identified to aid in program development. The literature review focused on the following topics related to oncology nurse navigation: metrics, program design, core competencies, and clinical roles. â&#x20AC;˘ The job description for the ONN was defined using standardized core competencies. The existing ONN was operating under a general oncology nursing job description that did not include role definitions germane to the ONN role, such as assessment of barriers, actions for Figure 1 Sequence of Events Leading to Program Development

Needs Assessment Completed

Survivorship Care Plans Developed and Survivorship Visits Initiated

Team Formation Monthly Planning Meetings

Screening Tools From Care Maps Used to Refer Patients to Appropriate Services

Disease-Specific Care Maps Developed

Obtained Budget Approval for a Total of 2.0 FTEs for Nurse Navigation

Getting Started: Creation of a Small Work Group

The concept of oncology nurse navigation in cancer care has been recognized as a vital, supportive component of patient care on the care continuum by the oncology community. Patients with cancer perceive ONN services as effective augmentations in the areas of patient education,

JONS-online.com journal of Oncology Navigation & Survivorship

19

nurse navigator program

guidance through the healthcare system, and patient education competencies. The job description for the ONN was developed using competencies from the National Coalition of Oncology Nurse Navigators (Figure 2).4 The integration of the standardized core competencies into the ONN job description provided structure to the new role and served as a framework for the decidedly diverse role. New hires to the ONN role benefited from the specifics of the job description as the role was clearly outlined as were detailed job expectations.

• The medical director and director of oncology services of the center’s department obtained administrative support at the facility’s executive level from the chief nursing officer and the vice president of patient care. The small work group met for 6 months and then used the information garnered from those meetings to launch an oncology nurse navigation development team.

Multidisciplinary Team Formation

Using information provided by the small work group, the main work team was created and goals were established.

The oncology nurse navigation development team sought to achieve quality outcomes in specific areas.

One goal was to increase the number of referrals to ancillary support services, including breast cancer support groups, nutritional services, financial coordination services, cancer rehabilitation, pulmonary rehabilitation, genetic counseling, and chemotherapy education classes.

The baseline volume for referrals to ancillary services prior to the initiation of the oncology nurse navigation program was less than optimal with a 60% attendance rate to chemotherapy education classes by all chemotherapy patients.

The breast cancer support group referrals were inadequate as well, reaching only 52% of all breast cancer patients.

The pulmonary rehabilitation and cancer rehabilitation departments consistently reported low referral numbers each quarter. The team sought to increase the percentages of referrals to ancillary services by 25% in the first 6 months of the program launch.

Given the excellent anecdotal patient satisfaction feedback from the pilot program, a second objective of the new program was to improve patient satisfaction over a wider range of the patients with cancer population. The existing pilot navigation program focused on only 1 disease site, breast cancer, and because the pilot program was a part-time position, the navigator was only able to reach approximately 70% of all breast cancer patients. The intention of the new program was to expand the population of patients under navigation by at least 3 disease sites and to increase the nurse navigation positions from 1 part-time nurse to 2 full-time nurses. It was also the aim of the oncology nurse navigation program to improve efficiency by reducing the wait time

20

october 2014 • Volume 5, number 5

from diagnosis to oncology consultation. The standard was set for patients to be seen by an oncologist within 1 week from the time of initial referral to the center. Prior to program initiation, the average wait time from initial referral to oncology consult in all disease sites was 11.9 days.

The team sought to meet the program goals would encompass the accreditation standards put forth by the CoC. The oncology nurse navigation development team consisted of multidisciplinary members including administrative staff, oncologists, oncology nurses, oncology clinical nurse specialists, social workers, pastoral care staff, and community support persons from the American Cancer Society.

The team met on a monthly basis and developed methods for assessment and guidance of the program.

Community Health Needs Assessment

In 2013, Saint Anthony Medical Center, along with a collaborative team of health professional experts and key community advocates, conducted a Community Health Needs Assessment (CHNA) in keeping with the federal requirement for tax-exempt hospitals.5 A CHNA is required to be conducted every 3 years and had last been completed by the collaborative team in 2010.

In the interest of meeting the specific needs of oncology patients in the service region and fulfilling the CoC requirements, the data provided by the CHNA were integrated into the guidelines for the oncology nurse navigation program. Specifically, the CHNA report indicated that obesity rates in the service region were higher than the state average, prompting the team to develop a consistent process for initiating cancer rehabilitative referrals within the care map algorithm. The CHNA report showed a regional increase of 11% over the past 3 years in persons reporting that they felt mentally unhealthy on most days. In light of the mental health data, the team developed a system to trigger social service referrals for patients based on the National Comprehensive Cancer Network (NCCN) distress tool score.6 The needs assessment tool provided through the Association of Community Cancer Centers (ACCC)7 was implemented as a means to identify areas that needed to be addressed prior to the initiation of the program.2,3 The tool also assisted the team in considering specific aspects of the navigation program. For example, the ACCC tool aided the team in decision-making regarding which disease sites would be adopted into the navigation program. The top 4 analytical disease sites were chosen: breast, prostate, colon, and lung.

Care Map Development

Once the needs assessment was complete, the information obtained was integrated into disease-specific care maps

AONNonline.org

A focus on the Commission on cancer

Figure 2 Job Description for Oncology Nurse Navigators POSITION SUMMARY:

The Oncology Nurse Navigator serves as a patient liaison to help patients and family members navigate the complex healthcare system. The Nurse Navigator will establish early contact with cancer patients to identify and eliminate barriers to timely diagnosis and treatment.

He/She will assess clinical, emotional, spiritual, psychosocial, financial, and other patient needs. This person works with a multidisciplinary team to provide improved comprehensive oncology services to patients. The Navigator will be responsible to monitor and report on outcomes measures. He/She will be responsible to schedule tests, procedures, appointments, and treatments, as well as initiate and complete the survivorship care plan. He/She will participate in multidisciplinary consultations and/or tumor conferences. He/She will refer patients to appropriate clinical trials as well as supportive care services. He/She will also direct patients and families to available community resources and supportive services, serve as a clinical resource with expertise in oncology care management in reinforcing education with patients and families, in addition to providing input on education materials.

MINIMUM EDUCATION:

GRADUATE OF ACCREDITED SCHOOL OF NURSING

PREFERRED EDUCATION:

Bachelor of Science in Nursing

MINIMUM EXPERIENCE:

5 YEARS’ ONCOLOGY EXPERIENCE IN THE ACUTE CARE OR OUTPATIENT SETTING

PREFERRED EXPERIENCE:

OCN

REQUIRED LICENSURE/ CERTIFICATION/REGISTRATION:

RN ILLINOIS

TECHNICAL COMPETENCE (This is what the employee will be evaluated on for his or her performance appraisals. Limit of 15) Professional, Legal, and Ethical Nursing Practice—The Oncology Nurse Navigator will integrate the philosophy of nursing care and evidence-based practice into care of the oncology patient.

1. D emonstrate proficiency in applying nursing theories, evidence-based nursing knowledge, problem-solving skills, and therapeutic techniques to perform professional nursing duties safely, legally, ethically, efficiently, and effectively.

2. K nowledge of pathophysiology of specific disease processes.

3. U nderstand oncology treatment modalities and rationale, including surgery, chemotherapy, symptom management, survivor care, surveillance, and radiation therapy.

4. U nderstand and apply current clinical guidelines in implementing treatment plan (ie, NCCN guidelines).

5. Lead the multidisciplinary treatment care plan and its implementation and evaluation.

6. P erform nursing techniques proficiently by maintaining accurate documentation, using appropriate channels of referral, and working effectively with other healthcare team members.

7. M anage physical, mental, psychosocial, and/or spiritual well-being while working with the patient to develop a treatment care plan and contribute to its implementation and evaluation.

Health Promotion and Health Education—The Oncology Nurse Navigator will implement specific therapeutic modalities to facilitate individualized care to the oncology patient in collaboration with the multidisciplinary team.

1. Develop a plan of care for the patient based on his or her own personal needs.

2. Perform a cancer risk assessment for patients with past, current, or potential diagnosis of cancer.

3. Assessment of hereditary predisposition and/or susceptibility to cancer.

4. Apply teaching-coaching philosophy when establishing patient relationships: a. Assessment of patient’s understanding of plan of care. b. Assist patient with understanding medical terminology.

5. Provide continuity of care throughout the entire cancer care experience from prediagnosis through survivorship, palliative/hospice care, and end of life: a. Remain a point of contact for the patient along the continuum of cancer care. b. Respond appropriately to instances of unsafe practice to safeguard the patient’s health.

6. Provide referrals to supportive resources at local, regional, and national levels.

7. Provide patient and family with appropriate educational materials regarding diagnosis, disease, and treatment.

Management and Leadership—The Oncology Nurse Navigator will promote the role of patient navigator to the public market and healthcare industry to ensure preservation of the role and advancement of the profession.

1. Participate in community educational outreach efforts to promote cancer screening guidelines.

2. Assess trends in patient care needs and development of services and resources to meet these needs.

3. Develop algorithms for care of stage-specific conditions, complying with cancer staging criteria.

4. A dvocate for the ONN role to other disciplines within the healthcare system and the community, including dialogue with other disciplines, such as cancer committee and multidisciplinary tumor board.

5. Implement a tracking system for data collection and benchmarking performance.

6. Communicate with cancer registrar to facilitate patient tracking.

Continued on page 22

JONS-online.com journal of Oncology Navigation & Survivorship

21

nurse navigator program

Figure 2 Job Description for Oncology Nurse Navigators...Continued from page 21 Advocacy—The Oncology Nurse Navigator will guide and direct the patient through a collaborative environment of healthcare disciplines to maintain dignity and autonomy of the individual patient.

1. Assessment of patient’s ability to navigate through the healthcare system and identify potential barriers (such as continuity, coordination of care, and communication with providers and the healthcare team).

2. Guide the patient through the healthcare system including: a. Appropriate referrals to insurance case manager/social worker to assist patient with insurance barriers. b. Ability to communicate among specialty practices within healthcare organization—build relationship with physicians and staff. c. Screen and inform patients who may be eligible for clinical trials for the advancement of oncology practice.

3. Educate and research issues related to diagnosis/treatment options and others pertinent to the patient.

4. Knowledge of cultural differences among diverse populations: a. Understand community demographics pertaining to health disparities. b. Knowledge of religious guidelines. c. Demonstrate cultural sensitivity. d. Utilize interpreter services as indicated.

5. Facilitate access to the appropriate services for individuals with disabilities.

6. Advocate for all patients’ equal access to cancer care regardless of financial status.

7. Advocate for the patient’s right to autonomy and an informed decision-making process.

(Figure 3) that were created to serve as algorithms for the ONNs to reference while navigating patients. The information included in the care maps was based upon guidelines from the NCCN and Oncology Nursing Society’s guidelines for oncology patient navigation.7,8 The development of the care maps by the multidisciplinary team has proven to be instrumental in both the improvement and the execution of the ONN program.

The care maps guide ONN actions that are vital in terms of meeting national guidelines for best practice, delineating scope of care, ensuring consistency in care delivery, and establishing clear strategies that positively impact outcomes. The care maps expedite diagnostic testing, staging, and treatment for patients, and also assure the integration of education, and supportive, palliative, and survivorship care. Validated screening tools have been incorporated into the care maps, enabling the ONN to properly assess patients and make appropriate referrals to ancillary services based upon the patients’ individual needs.9

Outcomes

For the first 6 months of the advent of the ONN program, all newly diagnosed patients with cancer of the breast, prostate, lung, and colon were navigated—a total of 202 patients. With the increased time and resources devoted to oncology nurse navigation, referrals have been more consistent to support groups, genetic counseling, cancer rehabilitation, pulmonary rehabilitation, hospice, and the American Cancer Society (Figure 3).

The implementation of the ONN program has led to a marked increase in attendance at the chemotherapy class offered in the department as well as increased attendance at the department’s breast cancer support group (Figure 3, Figure 4). In addition to boosting referrals to ancillary services, the oncology nurse navigation program has shown

22

october 2014 • Volume 5, number 5

indications of decreasing wait times from diagnosis to oncology consultation. Average time from diagnosis to consult decreased from 11.9 days (for all new patient referrals to the prenavigation program) to 5.5 days (for patients in the navigation program).

Survivorship Care Planning

The care maps include guidance for survivorship care planning recommended by NCCN6 and the survivorship section of the care maps have been integral in the development of the survivorship care planning process.

Currently, the survivorship care planning process includes a computer-based template that is populated with patient-specific information containing treatment dates and doses. The survivorship care plan information is finalized by the ONN and presented to the patient on the first follow-up visit with the oncologist after treatments are completed. The survivorship care plan is printed and included in a survivorship folder complete with information about the challenges of survivorship and resources for specific supportive programs. The survivorship care plan is faxed or mailed to the patient’s primary care physician once treatment and the survivorship visit have been completed.

Next Steps

The ONN program has proven to be a valuable service that positively promotes referrals to ancillary and community support services. The next steps for ongoing program improvement include the following: • Development of additional care maps for disease sites that will be added to the ONN program in the future—including cancers of the head and neck and pancreatic cancer.

• Streamlining the survivorship care planning tool and process to ensure all patients who have received naviga-

AONNonline.org

A focus on the Commission on cancer

Figure 3 Care Path—Breast at the OSF Center for Cancer Care

Patient Identification 1. Tumor Registry 2. Physicians 3. Women’s Center

Insurance Status

Have Insurance Meet with Financial Coordinator to: __ D iscuss insurance benefits, co-pays, co-pay assistance __ R efer to social work if appropriate

Navigator Checklist & Screening Tools __ NVS (Literacy Assessment) __ ACS Needs Assessment __ Health History __ Distress Thermometer __ Nutrition Score __ Genetics Screening __ Language & Sensory Evaluation __ Financial Coordinator __ Clinical Trials __ Support Group Information

No Insurance Meet with Financial Coordinator to: __ Assess eligibility for Medicare/Medicaid __ Review self-pay options, charity care,

low-cost insurance

**If there are eligibility issues that affect treatment— contact MD

Referral from Surgeon

Testing/Imaging Prior to Visit Imaging Studies: 1. Mammogram 2. I ndicators for breast MRI? (per MD recommendation) 3. PTE 4. CT scans 5. CXR

Medical Records: 1. Pathology report 2. I maging needs to be uploaded to PACS 3. Surgical or operative report 4. PCP progress notes 5. Patient medication list 6. Prior consultation report

Lab: CBC CMP Pregnancy test as indicated Molecular Testing: ER, PR, HER2/neu Radiation Therapy Chemotherapy Surgery Radiation

Decision Regarding Chemotherapy and/or Radiation Therapy (This is the first MD appt with either Radiation or MedOnc)

Surgery Chemotherapy +/- Reconstruction Implant Exchange Radiation

Treatment should start within 6-22 weeks of surgery

Surgery MammoSite Chemotherapy

Chemotherapy Is Not Indicated/Declined __ Rehab and physical therapy __ American Cancer Society consultation __ Advanced care planning __ Nutrition assessment __ Pain management __ Hospice referral __ Survivor care planning __ Support group

Before starting radiation __ P ostlumpectomy/

preradiation mammogram

Navigator confers with physician at day 120—then consults with patient

Lumpectomy Postop radiation MammoSite if: __ ≤2 cm __ LN negative __ Age ≥60 __ ER+ __ *At MD’s discretion

__ __ __ __ __ __ __ __ __ __

Mastectomy Radiation therapy if: __ LN+ __ ≥T3 __ +margins

Chemotherapy Candidate Rehab and physical therapy American Cancer Society consultation Advanced care planning Nutrition assessment Chemotherapy class scheduled NCCN guidelines for this patient’s stage Clinical trials MUGA scan Port placement Support group

Completion of Chemotherapy Survivorship Care Planning: __ Advanced care planning __ Nutrition consultation __ Rehab and physical therapy—Consult versus assessment only; specific weight loss and maintenance goal __ Lymphedema assessment __ PTSD Screening Tool—Psychologist/Psychiatrist referral if indicated __ Q1-3 monthly visit, physical examination __ 3-6 monthly CT scans of the chest __ Patient to be given list of symptoms of recurrence, and educated to notify MD early if they occur __ Support group __ Q6 months mammogram per NCCN guidelines (to radiated breast side) **Complete check-off in Epic Navigator Note Template**

JONS-online.com journal of Oncology Navigation & Survivorship

23

S:7"

a py

her

hab

y re

Phy

sic

al t

are

ec

Pul

mo

nar

iety

e/P alli

ativ

Soc

pic

an

eric

Am

Hos

Soc

Can

cer

etic

s

s

Gen

s

vic e

ser

ial

yc las

rap

the

mo

Che

Bre

ast

can

cer

sup

por

t

Number of patients navigated

Figure 4 Outcomes: Referrals to Ancillary Service

Table 2 (cont'd) MedDRA ver 10.0

HALAVEN (n=503) All Grades ≥ Grade 3

Control Group (n=247) All Grades ≥ Grade 3

Infections and Infestations Urinary Tract Infection 10% 1% 5% 0 Based upon laboratory data. b Includes neuropathy peripheral, neuropathy, peripheral motor neuropathy, polyneuropathy, peripheral sensory neuropathy, and paraesthesia. c Not applicable; (grading system does not specify > Grade 2 for alopecia).

Cytopenias: Grade 3 neutropenia occurred in 28% (143/503) of patients who received HALAVEN in Study 1, and 29% (144/503) of patients experienced Grade 4 neutropenia. Febrile neutropenia occurred in 5% (23/503) of patients; two patients (0.4%) died from complications of febrile neutropenia. Dose reduction due to neutropenia was required in 12% (62/503) of patients and discontinuation was required in <1% of patients. The mean time to nadir was 13 days and the mean time to recovery from severe neutropenia (<500/mm3) was 8 days. Grade 3 or greater thrombocytopenia occurred in 1% (7/503) of patients. G-CSF (granulocyte colony-stimulating factor) or GM-CSF (granulocyte–macrophage colony-stimulating factor) was used in 19% of patients who received HALAVEN. Peripheral Neuropathy: In Study 1, 17% of enrolled patients had Grade 1 peripheral neuropathy and 3% of patients had Grade 2 peripheral neuropathy at baseline. Dose reduction due to peripheral neuropathy was required by 3% (14/503) of patients who received HALAVEN. Four percent (20/503) of patients experienced peripheral motor neuropathy of any grade and 2% (8/503) of patients developed Grade 3 peripheral motor neuropathy.

Liver Function Test Abnormalities: Among patients with Grade 0 or 1 ALT levels at baseline, 18% of HALAVEN-treated patients experienced Grade 2 or greater ALT elevation. One HALAVEN-treated patient without documented liver metastases had concomitant Grade 2 elevations in bilirubin and ALT; these abnormalities resolved and did not recur with re-exposure to HALAVEN. Less Common Adverse Reactions: The following additional adverse reactions were reported in ≥5% to <10% of the HALAVEN-treated group: Eye Disorders: increased lacrimation; Gastrointestinal Disorders: dyspepsia, abdominal pain, stomatitis, dry mouth; General Disorders and Administration Site Conditions: peripheral edema; Infections and 1.respiratory Commission onMetabolism Cancer. Cancer Program Standards 2012: Ensuring PatientInfestations: upper tract infection; and Nutrition Disorders: hypokalemia; Musculoskeletal and Connective Centered Tissue Disorders: muscle spasms,1.2. muscular weakness; Nervous System Disorders: dysgeusia, Care.

Version http://www.facs.org/cancer/coc/programstandards dizziness; Psychiatric Disorders: insomnia, depression; Skin and Subcutaneous Tissue Disorders: rash.

2012.pdf.

Accessed July 24, 2014.

6.2 Postmarketing Experience 2. drug Campbell C,been Craig J, Eggert J, Bailey-Dorton C. Implementing The following adverse reactions have identified during post-approval of HALAVEN. Because these reactions are and meareported voluntarilysuring from a population of uncertainofsize, it is not always possible to reliably their frequency or community establish the impact patient navigation at aestimate comprehensive cana causal relationship to drug exposure. Blood and Lymphatic System Disorders: lymphopenia; Gastrointestinal cer center.

OncolDisorders: Nurs Forum.

Disorders: pancreatitis; Hepatobiliary hepatitis; 2010;37:61-68.

Immune System Disorders: drug hypersensitivity; Infections and 3.

Infestations: pneumonia, sepsis/neutropenic sepsis; aMetabolism and Nutrition Disorders: Christensen D, Bellomo C. Using nurse navigation pathway in the timehypomagnesemia, dehydration; Respiratory, thoracic, and mediastinal disorders: interstitial lung disease; ly care of oncology patients.Tissue J Oncol Navpruritus. & Survivorship. 2014;5:13-18.

Psychiatric Disorders: anxiety; Skin and Subcutaneous Disorders: 8 USE IN SPECIFIC POPULATIONS 4. National Coalition of Oncology Nurse Navigators. www.nconn.org. Ac8.1 Pregnancy Category D cessed August 6, 2014.

There are no adequate and well-controlled studies with HALAVEN in pregnant women. HALAVEN is a microtubule inhibitor; 5. http://www.irs.gov/Charities-&-Non-Profits/Charitable-Organizations/Newtherefore, it is expected to cause fetal harm when administered to a pregnant woman. Embryo-fetal toxicity and teratogenicity occurred in rats thatRequirements-for-501(c)(3)-Hospitals-Under-the-Affordable-Care-Act. received eribulin mesylate at approximately half of the recommended human dose based on body surface area. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be Accessed August apprised of the potential hazard to the fetus. 26, 2014.

In a developmental toxicity study, pregnant rats received intravenousCancer infusion of eribulin mesylate during organogenesis (Gestation 6. National Comprehensive Network. www.nccn.com.

Accessed July Days 8, 10, and 12) at doses approximately 0.04, 0.13, 0.43 and 0.64 times the recommended human dose, based on body surface 28, 2014. area (mg/m2). Increased abortion and severe external or soft tissue malformations were observed in offspring at doses 0.64 times the 7.dose Association of Community Cancer Centers. www.accc-cancerorg/resources/ recommended human based on body surface area (mg/m2), including the absence of a lower jaw, tongue, stomach and spleen.

Increased embryo-fetal death/resorption, reduced fetal weights, and minor skeletal anomalies consistent with developmental delay pdf/PNTOOLS/Pre-Assessment-Tool.pdf.

Accessed July 24, 2014. were also reported at or above doses of 0.43 times the recommended human dose.

Oncology Oncology Society, the(mg/m²), Association of Maternal toxicity of8. eribulin mesylate wasNursing reported in ratsSociety. at or above doses of 0.43 timesNursing the recommended human dose and included enlarged spleen, reducedSocial maternal Work, weight gainand and decreased food consumption.

Oncology the National Association of Social Workers Joint 8.3 Nursing Position Mothers on the Role of Oncology Nursing and Oncology Social Work in It is not known whether HALAVEN is excreted into human milk. No studies in humans or animals were conducted to determine Patient https://www.ons.org/about-ons/ons-position-statements/ if HALAVEN is excreted into milk.Navigation.

Because many drugs are excreted into human milk and because of the potential for serious adverse reactions ineducation-certification-and-role-delineation/oncology-nursing-0. human milk fed infants from HALAVEN, a decision should be made whether to discontinue nursing or to Accessed discontinue HALAVEN taking into account the importance of the drug to the mother.

8.4 PediatricJuly Use 28, 2014.

9. Swanson J, inKoch Thebelow role of ofthe oncology nurse navigator in distress The safety and effectiveness of HALAVEN pediatricL. patients the age 18 years have not been established.

8.6 Hepatic management Impairment of adult inpatients with cancer: a retrospective study. Oncol 2 2 Administration of HALAVEN at a dose of 1.1 mg/m to patients with mild hepatic impairment and 0.7 mg/m to patients with Nurs Forum. moderate hepatic impairment resulted in2010;37:69-76. similar exposure to eribulin as a dose of 1.4 mg/m2 to patients with normal hepatic 2 function. Therefore, a lower starting dose of 1.1 mg/m is recommended for patients with mild hepatic impairment (Child-Pugh A) and of 0.7 mg/m2 is recommended for patients with moderate hepatic impairment (Child-Pugh B). HALAVEN was not studied in patients with severe hepatic impairment (Child-Pugh C).

8.7 Renal Impairment For patients with moderate renal impairment (CrCl 30-50 mL/min), the geometric mean dose-normalized systemic exposure increased 2-fold compared to patients with normal renal function. A lower starting dose of 1.1 mg/m2 is recommended for patients with moderate renal impairment. The safety of HALAVEN was not studied in patients with severe renal impairment (CrCl <30 mL/min).

10 OVERDOSAGE Overdosage of HALAVEN has been reported at approximately 4 times the recommended dose, which resulted in Grade 3 neutropenia lasting seven days and a Grade 3 hypersensitivity reaction lasting one day.

There is no known antidote for HALAVEN overdose.

12 CLINICAL PHARMACOLOGY 12.3 Pharmacokinetics ® Specific Populations Hepatic Impairment A study evaluated the PK of eribulin in patients with mild (Child-Pugh A; n=7) and moderate (Child-Pugh B; n=5) hepatic impairment.

Compared to patients with normal hepatic function (n=6), eribulin exposure increased 1.8-fold and 2.5-fold in patients with mild and moderate hepatic impairment, respectively. Administration of HALAVEN at a dose of 1.1 mg/m2 to patients with mild hepatic impairment and 0.7 mg/m2 to patients with moderate hepatic impairment resulted in similar exposure to eribulin as a dose of 1.4 mg/m2 to patients with normal hepatic function.

Renal Impairment No formal PK trials were conducted with HALAVEN in patients with renal impairment. Available data suggests that geometric mean dose-normalized systemic exposure is similar for patients with mild renal impairment (CrCl 50-80 mL/min) relative to patients with normal renal function. However, for patients with moderate renal impairment (CrCl 30-50 mL/min), the geometric mean dose-normalized systemic exposure increased 2-fold compared to patients with normal renal function.

12.6 Cardiac Electrophysiology The effect of HALAVEN on the QTc interval was assessed in an open-label, uncontrolled, multicenter, single-arm dedicated QT trial. A total of 26 patients with solid tumors received 1.4 mg/m2 of HALAVEN on Days 1 and 8 of a 21-day cycle. A delayed QTc prolongation was observed on Day 8, with no prolongation observed on Day 1. The maximum mean QTcF change from baseline (95% upper confidence interval) was 11.4 (19.5) ms.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, mutagenesis, impairment of fertility Carcinogenicity studies have not been conducted with eribulin mesylate.

Eribulin mesylate was not mutagenic in in vitro bacterial reverse mutation assays (Ames test). Eribulin mesylate was positive in mouse lymphoma mutagenesis assays, and was clastogenic in an in vivo rat bone marrow micronucleus assay.

The effects of HALAVEN on human fertility are unknown. Fertility studies have not been conducted with eribulin mesylate in humans or animals. However, nonclinical findings in repeated-dose dog and rat toxicology studies suggest that male fertility may be compromised by treatment with eribulin mesylate. Rats exhibited testicular toxicity (hypocellularity of seminiferous epithelium with hypospermia/aspermia) following dosing with eribulin mesylate at or above 0.43 times the recommended human dose (mg/m2) given once weekly for 3 weeks, or at or above 0.21 times the recommended human dose (mg/m2) given once weekly for 3 out of 5 weeks, repeated for 6 cycles. Testicular toxicity was also observed in dogs given 0.64 times the recommended human dose (mg/m2) weekly for 3 out of 5 weeks, repeated for 6 cycles.

17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling • Advise patients to contact their health care provider for a fever of 100.5°F or greater or other signs or symptoms of infection such as chills, cough, or burning or pain on urination.

• Advise women of childbearing potential to avoid pregnancy and to use effective contraception during treatment with HALAVEN. a

Corresponding Author: Peggy Malone, RN, BS, OCN, OSF Saint Anthony Center for Cancer Care, 5666 East State Street, Rockford, IL 61008. E-mail: Peggy.e.malone@osf healthcare.org

References

Author Disclosure Statement: All authors have nothing to disclose.

Call for Papers

The Journal of Oncology Navigation & Survivorship (JONS), launched in 2010, is the nation’s first peer-reviewed clinical journal for Oncology Nurse and Patient Navigators. As this critical area of specialty and expertise grows, research and sharing of best practices are integral to both improving the clinical care of cancer patients as well as expanding the existing literature and knowledge base. Our goal at JONS is to help facilitate that growth.

Papers can be in the following forms: • Original Research • Case Study • Review Article (a synopsis/review of current • “How To” article designed to transfer literature in a specific area of research) successes to fellow practitioners Each manuscript is subject to an internal review to see that it fits the scope and mission of our journal. Papers that pass the initial review could be subject to a blind peer review; final acceptance is based on that review.

If you are interested in submitting a paper or have any questions, please feel free to visit our website www.JONS-online.com or e-mail our editorial department at fevans@the-lynx-group.com.

24

october 2014 • Volume 5, number 5

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– HALAVEN® is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd. © 2013 Eisai Inc. All rights reserved. Printed in USA / November 2013 HALA0475

AONNonline.org

T:10.5"

tor services are provided with a survivorship care plan upon treatment completion.

• Implementation of a patient satisfaction survey for the oncology nurse navigation program. g

S:10"

HALAVEN® (eribulin mesylate) Injection BRIEF SUMMARY – See package insert for full prescribing information.

2.2 nurse Dose Modification navigator Assess for peripheral neuropathy and obtain complete blood cell counts prior to each dose. program Recommended dose delays • Do not administer HALAVEN on Day 1 or Day 8 for any of the following: – ANC <1,000/mm3 – Platelets <75,000/mm3 – Grade 3 or 4 non-hematological toxicities.

• The Day 8 dose may be delayed for a maximum of 1 week.

– If toxicities do not resolve or improve to ≤ Grade 2 severity by Day 15, omit the dose.

– If toxicities resolve or improve to ≤ Grade 2 severity by Day 15, administer HALAVEN at a reduced dose and initiate the next cycle no sooner than 2 weeks later.

Recommended dose reductions • If a dose has been delayed for toxicity and toxicities have recovered to Grade 2 severity or less, resume HALAVEN at a reduced dose as set out in Table 1.

225 • Do not re-escalate HALAVEN dose after it has been reduced.

Table 1 Recommended Dose Reductions 200 Recommended Event Description HALAVEN Dose 175 2 Permanently reduce the 1.4 mg/m HALAVEN dose for any of the following: ANC <500/mm3 for >7 days 150 ANC <1,000 /mm3 with fever or infection 1.1 mg/m2 Platelets <25,000/mm3 125 Platelets <50,000/mm3 requiring transfusion Non-hematologic Grade 3 or 4 toxicities 100 Omission or delay of Day 8 HALAVEN dose in previous cycle for toxicity 75 dose reduction while receiving 1.1 mg/m2 Occurrence of any event requiring permanent 0.7 mg/m2 Occurrence of any event requiring permanent dose reduction while receiving 0.7 mg/m2 Discontinue HALAVEN 50 ANC = absolute neutrophil count.

Toxicities graded in accordance with National25 Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

5 WARNINGS AND PRECAUTIONS 5.1 Neutropenia 0 Severe neutropenia (ANC <500/mm3) lasting more than one week occurred in 12% (62/503) of patients in Study 1, leading to discontinuation in <1% of patients. Patients with alanine aminotransferase or aspartate aminotransferase >3 × ULN (upper limit of normal) experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal aminotransferase levels. Patients with bilirubin >1.5 × ULN also had a higher incidence of Grade 4 neutropenia and febrile neutropenia.

Monitor complete blood counts prior to each dose; increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias.

Delay administration of HALAVEN and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days. Clinical studies of HALAVEN did not include patients with baseline neutrophil counts below 1,500/mm3.

5.2 Peripheral Neuropathy Grade 3 peripheral neuropathy occurred in 8% (40/503) of patients, and Grade 4 in 0.4% (2/503) of patients in Study 1. Peripheral neuropathy was the most common toxicity leading to discontinuation of HALAVEN (5% of patients; 24/503). Neuropathy lasting more than one year occurred in 5% (26/503) of patients. Twenty-two percent (109/503) of patients developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Monitor patients closely for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

5.3 Embryo-Fetal Toxicity There are no adequate and well-controlled studies of HALAVEN in pregnant women. HALAVEN is a microtubule inhibitor; therefore, it is expected to cause fetal harm when administered to a pregnant woman. Embryo-fetal toxicity and teratogenicity occurred in rats that received eribulin mesylate at approximately half of the recommended human dose based on body surface area. If this drug is used during pregnancy, or if a patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus.

5.4 QT Prolongation In an uncontrolled open-label ECG study in 26 patients, QT prolongation was observed on Day 8, independent of eribulin concentration, with no QT prolongation observed on Day 1. ECG monitoring is recommended if therapy is initiated in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid HALAVEN in patients with congenital long QT syndrome.

6 ADVERSE REACTIONS 6.1 Clinical Trials Experience The following adverse reactions are discussed in detail in other sections of the labeling: • Neutropenia • Peripheral neuropathy • QT interval prolongation The most common adverse reactions (≥25%) reported in patients receiving HALAVEN were neutropenia, anemia, asthenia/ fatigue, alopecia, peripheral neuropathy, nausea, and constipation. The most common serious adverse reactions reported in patients receiving HALAVEN were febrile neutropenia (4%) and neutropenia (2%). The most common adverse reaction resulting in discontinuation of HALAVEN was peripheral neuropathy (5%).

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.

In clinical trials, HALAVEN has been administered to 1,222 patients with multiple tumor types, including 240 patients exposed to HALAVEN for 6 months or longer. The majority of the 1,222 patients were women (82%) with a median age of 58 years (range: 26 to 91 years). The racial and ethnic distribution was Caucasian (83%), Black (5%), Asian (2%), and other (5%).

The adverse reactions described in Table 2 were identified in 750 patients treated in Study 1. In Study 1, patients were randomized (2:1) to receive either HALAVEN (1.4 mg/m2 on Days 1 and 8 of a 21-day cycle) or single agent treatment chosen by their physician (control group). A total of 503 patients received HALAVEN, and 247 patients in the control group received therapy consisting of chemotherapy [total 97% (anthracyclines 10%, capecitabine 18%, gemcitabine 19%, taxanes 15%, vinorelbine 25%, other chemotherapies 10%)] or hormonal therapy (3%). The median duration of exposure was 118 days for patients receiving HALAVEN and 63 days for patients receiving control therapy. Table 2 reports the most common adverse reactions occurring in at least 10% of patients in either group.

Table 2 Adverse Reactions with a Per-Patient Incidence of at Least 10% in Study 1 MedDRA ver 10.0 HALAVEN (n=503) Control Group (n=247) All Grades ≥ Grade 3 All Grades ≥ Grade 3 a Blood and Lymphatic System Disorders Neutropenia 82% 57% 53% 23% Anemia 58% 2% 55% 4% Nervous system disorders Peripheral neuropathyb 35% 8% 16% 2% Headache 19% <1% 12% <1% General disorders and administrative site conditions Asthenia/Fatigue 54% 10% 40% 11% Mucosal inflammation 9% 1% 10% 2% Pyrexia 21% <1% 13% <1% Gastrointestinal disorders Constipation 25% 1% 21% 1% Diarrhea 18% 0 18% 0 Nausea 35% 1% 28% 3% Vomiting 18% 1% 18% 1% Musculoskeletal and connective tissue disorders Arthralgia/Myalgia 22% <1% 12% 1% Back pain 16% 1% 7% 2% Bone pain 12% 2% 9% 2% Pain in extremity 11% 1% 10% 1% Investigations Weight decreased 21% 1% 14% <1% Metabolism and nutrition disorders Anorexia 20% 1% 13% 1% Respiratory, thoracic, and mediastinal disorders Cough 14% 0 9% 0 Dyspnea 16% 4% 13% 4% Skin and subcutaneous tissue disorders Alopecia 45% NAc 10% NAc

Navigate

THE EVOLVING MBC LANDSCAPE...

Indication

Halaven is indicated for the treatment of patients with metastatic breast cancer (MBC) who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease.

Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

Please see Important Safety Information on the following spread and accompanying brief summary of Halaven full Prescribing Information.

HALAVEN Ž is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd. Š 2013 Eisai Inc. All rights reserved.

Printed in USA/November 2013 HALA0479

IN MBC, ONCOLOGISTS ARE CONSISTENTLY

EXTENDING THE CONTINUUM OF MEANINGFUL CARE1-3 With MBC treatment potentially extending to 6 lines and beyond, third-line chemotherapy can still be early in the fight for some patients2

LINES OF THERAPY GIVEN

1L 2L

3L 4L

2001 and earlier4

5L 6L 7L+

2005-20093,5

2010-20112,6

Indication Halaven is indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

Important Safety Information Neutropenia

Monitor complete blood counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days Severe neutropenia (ANC <500/mm3) lasting more than 1 week occurred in 12% (62/503) of patients. Patients with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels Grade 3 and Grade 4 neutropenia occurred in 28% and 29%, respectively, of patients who received Halaven. Febrile neutropenia occurred in 5% of patients and two patients (0.4%) died from complications

Peripheral Neuropathy Patients should be monitored closely for signs of peripheral motor and sensory neuropathy

Grade 3 peripheral neuropathy occurred in 8% of patients, and Grade 4 in 0.4% of patients who received Halaven. Delay administration of Halaven until resolution to Grade 2 or less Neuropathy lasting more than 1 year occurred in 5% of patients. Twenty-two percent of patients developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days) Peripheral neuropathy (5%) was the most common adverse reaction resulting in discontinuation

Pregnancy Category D Halaven is expected to cause fetal harm when administered to a pregnant woman and patients should be advised of these risks

QT Prolongation In an uncontrolled ECG study in 26 patients, QT prolongation was observed on Day 8, independent of eribulin concentration, with no prolongation on Day 1. ECG monitoring is recommended for patients with congestive heart failure; bradyarrhythmias;

HALAVEN ® is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd. © 2013 Eisai Inc. All rights reserved.

Printed in USA/November 2013 HALA0479

GIVE YOUR PATIENTS

AN OPPORTUNITY FOR MORE LIFE The FIRST and ONLY single agent that significantly extended OVERALL SURVIVAL in third-line MBC7-14

UPDATED OVERALL SURVIVAL (OS) ANALYSIS (UNPLANNED): MEDIAN OS, MONTHS (95% CI)1,15,a

P R O P O R T I O N O F PAT I E N T S A L I V E

1.0 0.9 0.8

Halaven

0.77

25% (2.6 month)

(n=508)

13.2

INCREASE

(12.1, 14.4)

0.6

IN MEDIAN OS

Deaths=386

0.5

Treatment of Physician’s Choice

0.4

(n=254)

0.3

10.6

0.2

(9.2, 12.0)

0.1

Deaths=203

0.0 0

6

12

18

24

30

36

54 26

11 5

0 Halaven 0 TPC

TIME (MONTHS)

Number of patients at risk

508 254

406 178

274 106

142 61

Results from an updated, unplanned survival analysis of the Phase III, randomized, openlabel, multicenter, multinational Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice versus E7389 (Eribulin) (EMBRACE) trial of Halaven versus Treatment of Physician’s Choice (TPC) in patients with MBC (N=762), conducted when 77% of events (deaths) had been observed. The primary endpoint was OS. Patients were randomized (2:1) to receive either Halaven 1.4 mg/m2 intravenously for 2 to 5 minutes on Days 1 and 8 of a 21-day cycle, or any singleagent therapy, selected prior to randomization.

At baseline, all patients had received ≥2 prior chemotherapeutic regimens for metastatic disease and demonstrated disease progression within 6 months of their last chemotherapeutic regimen. All patients received prior anthracyclineand taxane-based chemotherapy, unless contraindicated. Therapies in the TPC arm consisted of 97% chemotherapy (26% vinorelbine, 18% gemcitabine, 18% capecitabine, 16% taxanes [included paclitaxel, docetaxel, nab-paclitaxel, and ixabepilone], 9% anthracyclines, 10% other chemotherapy), and 3% hormonal therapy.

CI=confidence interval.

Conducted in the intent-to-treat population.

a

The updated OS analysis was consistent with the primary analysis7 The primary analysis, conducted when ~50% of events (deaths) had been observed, demonstrated a median OS for Halaven vs TPC of 13.1 months (95% CI: 11.8, 14.3) vs 10.6 months (95% CI: 9.3, 12.5), hazard ratio=0.81 (95% CI: 0.66, 0.99) (P=0.041)7,15

concomitant use of drugs that prolong QT interval, including Class Ia and III antiarrhythmics; and electrolyte abnormalities Correct hypokalemia or hypomagnesemia prior to initiating Halaven and monitor electrolytes periodically during therapy.

Avoid in patients with congenital long QT syndrome

Hepatic and Renal Impairment For patients with mild (Child-Pugh A) or moderate (ChildPugh B) hepatic and/or moderate (CrCl 30-50 mL/min) renal impairment, a reduction in starting dose is recommended

Most Common Adverse Reactions Most common adverse reactions (≥25%) reported in patients receiving Halaven were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%) The most common serious adverse reactions reported in patients receiving Halaven were febrile neutropenia (4%) and neutropenia (2%)

References: 1. Dufresne A, et al. Breast Cancer Res Treat. 2008;107(2):275-279.

2. Planchat E, et al. Breast. 2011;20(6):574-578. 3. Ray S, et al. In: J Clin Oncol.

San Francisco, CA: ASCO Breast Cancer Symposium; 2012. Abstract 116.

4. Cardoso F, et al. Ann Oncol. 2002;13(2):197-207. 5. Seah DS, et al. Poster presented at: 2012 ASCO Annual Meeting; June 1–5, 2012; Chicago, IL. Abstract 6089. 6. Lin NU, et al. Lancet. 2011;377(9769):878-880. 7. Halaven [package insert]. Woodcliff Lake, NJ: Eisai Inc; 2013. 8. Saad ED, et al. J Clin Oncol. 2010;28(11):1958-1962. 9. Slamon DJ, et al.

N Engl J Med. 2001;344(11):783-792. 10. Geyer CE, et al. N Engl J Med. 2006;355(26): 2733-2743. 11. von Minckwitz G, et al. J Clin Oncol. 2009;27(12):1999-2006.

12. Miller K, et al. N Engl J Med. 2007;357(26):2666-2676. 13. Robert NJ, et al.

J Clin Oncol. 2011;29(10):1252-1260. 14. Sparano JA, et al. J Clin Oncol. 2010;28(20): 3256-3263. 15. Cortes J, et al. Lancet. 2011;377(9769):914-923.

Please see accompanying brief summary of Halaven full Prescribing Information.

Visit www.halaven.com/hcp.aspx

S:7"

Table 2 (cont'd) MedDRA ver 10.0

HALAVEN (n=503) All Grades ≥ Grade 3

Control Group (n=247) All Grades ≥ Grade 3

Infections and Infestations Urinary Tract Infection 10% 1% 5% 0 Based upon laboratory data. b Includes neuropathy peripheral, neuropathy, peripheral motor neuropathy, polyneuropathy, peripheral sensory neuropathy, and paraesthesia. c Not applicable; (grading system does not specify > Grade 2 for alopecia).

Cytopenias: Grade 3 neutropenia occurred in 28% (143/503) of patients who received HALAVEN in Study 1, and 29% (144/503) of patients experienced Grade 4 neutropenia. Febrile neutropenia occurred in 5% (23/503) of patients; two patients (0.4%) died from complications of febrile neutropenia. Dose reduction due to neutropenia was required in 12% (62/503) of patients and discontinuation was required in <1% of patients. The mean time to nadir was 13 days and the mean time to recovery from severe neutropenia (<500/mm3) was 8 days. Grade 3 or greater thrombocytopenia occurred in 1% (7/503) of patients. G-CSF (granulocyte colony-stimulating factor) or GM-CSF (granulocyte–macrophage colony-stimulating factor) was used in 19% of patients who received HALAVEN. Peripheral Neuropathy: In Study 1, 17% of enrolled patients had Grade 1 peripheral neuropathy and 3% of patients had Grade 2 peripheral neuropathy at baseline. Dose reduction due to peripheral neuropathy was required by 3% (14/503) of patients who received HALAVEN. Four percent (20/503) of patients experienced peripheral motor neuropathy of any grade and 2% (8/503) of patients developed Grade 3 peripheral motor neuropathy.

Liver Function Test Abnormalities: Among patients with Grade 0 or 1 ALT levels at baseline, 18% of HALAVEN-treated patients experienced Grade 2 or greater ALT elevation. One HALAVEN-treated patient without documented liver metastases had concomitant Grade 2 elevations in bilirubin and ALT; these abnormalities resolved and did not recur with re-exposure to HALAVEN. Less Common Adverse Reactions: The following additional adverse reactions were reported in ≥5% to <10% of the HALAVEN-treated group: Eye Disorders: increased lacrimation; Gastrointestinal Disorders: dyspepsia, abdominal pain, stomatitis, dry mouth; General Disorders and Administration Site Conditions: peripheral edema; Infections and Infestations: upper respiratory tract infection; Metabolism and Nutrition Disorders: hypokalemia; Musculoskeletal and Connective Tissue Disorders: muscle spasms, muscular weakness; Nervous System Disorders: dysgeusia, dizziness; Psychiatric Disorders: insomnia, depression; Skin and Subcutaneous Tissue Disorders: rash.

6.2 Postmarketing Experience The following adverse drug reactions have been identified during post-approval of HALAVEN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: lymphopenia; Gastrointestinal Disorders: pancreatitis; Hepatobiliary Disorders: hepatitis; Immune System Disorders: drug hypersensitivity; Infections and Infestations: pneumonia, sepsis/neutropenic sepsis; Metabolism and Nutrition Disorders: hypomagnesemia, dehydration; Respiratory, thoracic, and mediastinal disorders: interstitial lung disease; Psychiatric Disorders: anxiety; Skin and Subcutaneous Tissue Disorders: pruritus.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Category D There are no adequate and well-controlled studies with HALAVEN in pregnant women. HALAVEN is a microtubule inhibitor; therefore, it is expected to cause fetal harm when administered to a pregnant woman. Embryo-fetal toxicity and teratogenicity occurred in rats that received eribulin mesylate at approximately half of the recommended human dose based on body surface area. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

In a developmental toxicity study, pregnant rats received intravenous infusion of eribulin mesylate during organogenesis (Gestation Days 8, 10, and 12) at doses approximately 0.04, 0.13, 0.43 and 0.64 times the recommended human dose, based on body surface area (mg/m2). Increased abortion and severe external or soft tissue malformations were observed in offspring at doses 0.64 times the recommended human dose based on body surface area (mg/m2), including the absence of a lower jaw, tongue, stomach and spleen.

Increased embryo-fetal death/resorption, reduced fetal weights, and minor skeletal anomalies consistent with developmental delay were also reported at or above doses of 0.43 times the recommended human dose.

Maternal toxicity of eribulin mesylate was reported in rats at or above doses of 0.43 times the recommended human dose (mg/m²), and included enlarged spleen, reduced maternal weight gain and decreased food consumption.

8.3 Nursing Mothers It is not known whether HALAVEN is excreted into human milk. No studies in humans or animals were conducted to determine if HALAVEN is excreted into milk. Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in human milk fed infants from HALAVEN, a decision should be made whether to discontinue nursing or to discontinue HALAVEN taking into account the importance of the drug to the mother.

8.4 Pediatric Use The safety and effectiveness of HALAVEN in pediatric patients below the age of 18 years have not been established.

8.6 Hepatic Impairment Administration of HALAVEN at a dose of 1.1 mg/m2 to patients with mild hepatic impairment and 0.7 mg/m2 to patients with moderate hepatic impairment resulted in similar exposure to eribulin as a dose of 1.4 mg/m2 to patients with normal hepatic function. Therefore, a lower starting dose of 1.1 mg/m2 is recommended for patients with mild hepatic impairment (Child-Pugh A) and of 0.7 mg/m2 is recommended for patients with moderate hepatic impairment (Child-Pugh B). HALAVEN was not studied in patients with severe hepatic impairment (Child-Pugh C).

8.7 Renal Impairment For patients with moderate renal impairment (CrCl 30-50 mL/min), the geometric mean dose-normalized systemic exposure increased 2-fold compared to patients with normal renal function. A lower starting dose of 1.1 mg/m2 is recommended for patients with moderate renal impairment. The safety of HALAVEN was not studied in patients with severe renal impairment (CrCl <30 mL/min).

10 OVERDOSAGE Overdosage of HALAVEN has been reported at approximately 4 times the recommended dose, which resulted in Grade 3 neutropenia lasting seven days and a Grade 3 hypersensitivity reaction lasting one day.

There is no known antidote for HALAVEN overdose.

12 CLINICAL PHARMACOLOGY 12.3 Pharmacokinetics Specific Populations Hepatic Impairment A study evaluated the PK of eribulin in patients with mild (Child-Pugh A; n=7) and moderate (Child-Pugh B; n=5) hepatic impairment.

Compared to patients with normal hepatic function (n=6), eribulin exposure increased 1.8-fold and 2.5-fold in patients with mild and moderate hepatic impairment, respectively. Administration of HALAVEN at a dose of 1.1 mg/m2 to patients with mild hepatic impairment and 0.7 mg/m2 to patients with moderate hepatic impairment resulted in similar exposure to eribulin as a dose of 1.4 mg/m2 to patients with normal hepatic function.

Renal Impairment No formal PK trials were conducted with HALAVEN in patients with renal impairment. Available data suggests that geometric mean dose-normalized systemic exposure is similar for patients with mild renal impairment (CrCl 50-80 mL/min) relative to patients with normal renal function. However, for patients with moderate renal impairment (CrCl 30-50 mL/min), the geometric mean dose-normalized systemic exposure increased 2-fold compared to patients with normal renal function.

12.6 Cardiac Electrophysiology The effect of HALAVEN on the QTc interval was assessed in an open-label, uncontrolled, multicenter, single-arm dedicated QT trial. A total of 26 patients with solid tumors received 1.4 mg/m2 of HALAVEN on Days 1 and 8 of a 21-day cycle. A delayed QTc prolongation was observed on Day 8, with no prolongation observed on Day 1. The maximum mean QTcF change from baseline (95% upper confidence interval) was 11.4 (19.5) ms.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, mutagenesis, impairment of fertility Carcinogenicity studies have not been conducted with eribulin mesylate.

Eribulin mesylate was not mutagenic in in vitro bacterial reverse mutation assays (Ames test). Eribulin mesylate was positive in mouse lymphoma mutagenesis assays, and was clastogenic in an in vivo rat bone marrow micronucleus assay.

The effects of HALAVEN on human fertility are unknown. Fertility studies have not been conducted with eribulin mesylate in humans or animals. However, nonclinical findings in repeated-dose dog and rat toxicology studies suggest that male fertility may be compromised by treatment with eribulin mesylate. Rats exhibited testicular toxicity (hypocellularity of seminiferous epithelium with hypospermia/aspermia) following dosing with eribulin mesylate at or above 0.43 times the recommended human dose (mg/m2) given once weekly for 3 weeks, or at or above 0.21 times the recommended human dose (mg/m2) given once weekly for 3 out of 5 weeks, repeated for 6 cycles. Testicular toxicity was also observed in dogs given 0.64 times the recommended human dose (mg/m2) weekly for 3 out of 5 weeks, repeated for 6 cycles.

17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling • Advise patients to contact their health care provider for a fever of 100.5°F or greater or other signs or symptoms of infection such as chills, cough, or burning or pain on urination.

• Advise women of childbearing potential to avoid pregnancy and to use effective contraception during treatment with HALAVEN. a

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––– HALAVEN® is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd. © 2013 Eisai Inc. All rights reserved. Printed in USA / November 2013 HALA0475

S:10"

HALAVEN® (eribulin mesylate) Injection BRIEF SUMMARY – See package insert for full prescribing information.

2.2 Dose Modification Assess for peripheral neuropathy and obtain complete blood cell counts prior to each dose.

Recommended dose delays • Do not administer HALAVEN on Day 1 or Day 8 for any of the following: – ANC <1,000/mm3 – Platelets <75,000/mm3 – Grade 3 or 4 non-hematological toxicities.

• The Day 8 dose may be delayed for a maximum of 1 week.

– If toxicities do not resolve or improve to ≤ Grade 2 severity by Day 15, omit the dose.

– If toxicities resolve or improve to ≤ Grade 2 severity by Day 15, administer HALAVEN at a reduced dose and initiate the next cycle no sooner than 2 weeks later.

Recommended dose reductions • If a dose has been delayed for toxicity and toxicities have recovered to Grade 2 severity or less, resume HALAVEN at a reduced dose as set out in Table 1.

• Do not re-escalate HALAVEN dose after it has been reduced.

Table 1 Recommended Dose Reductions Recommended Event Description HALAVEN Dose 2 Permanently reduce the 1.4 mg/m HALAVEN dose for any of the following: ANC <500/mm3 for >7 days ANC <1,000 /mm3 with fever or infection 1.1 mg/m2 Platelets <25,000/mm3 Platelets <50,000/mm3 requiring transfusion Non-hematologic Grade 3 or 4 toxicities Omission or delay of Day 8 HALAVEN dose in previous cycle for toxicity Occurrence of any event requiring permanent dose reduction while receiving 1.1 mg/m2 0.7 mg/m2 Occurrence of any event requiring permanent dose reduction while receiving 0.7 mg/m2 Discontinue HALAVEN ANC = absolute neutrophil count.

Toxicities graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

5 WARNINGS AND PRECAUTIONS 5.1 Neutropenia Severe neutropenia (ANC <500/mm3) lasting more than one week occurred in 12% (62/503) of patients in Study 1, leading to discontinuation in <1% of patients. Patients with alanine aminotransferase or aspartate aminotransferase >3 × ULN (upper limit of normal) experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal aminotransferase levels. Patients with bilirubin >1.5 × ULN also had a higher incidence of Grade 4 neutropenia and febrile neutropenia.

Monitor complete blood counts prior to each dose; increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias.

Delay administration of HALAVEN and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days. Clinical studies of HALAVEN did not include patients with baseline neutrophil counts below 1,500/mm3.

5.2 Peripheral Neuropathy Grade 3 peripheral neuropathy occurred in 8% (40/503) of patients, and Grade 4 in 0.4% (2/503) of patients in Study 1. Peripheral neuropathy was the most common toxicity leading to discontinuation of HALAVEN (5% of patients; 24/503). Neuropathy lasting more than one year occurred in 5% (26/503) of patients. Twenty-two percent (109/503) of patients developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Monitor patients closely for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

5.3 Embryo-Fetal Toxicity There are no adequate and well-controlled studies of HALAVEN in pregnant women. HALAVEN is a microtubule inhibitor; therefore, it is expected to cause fetal harm when administered to a pregnant woman. Embryo-fetal toxicity and teratogenicity occurred in rats that received eribulin mesylate at approximately half of the recommended human dose based on body surface area. If this drug is used during pregnancy, or if a patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus.

5.4 QT Prolongation In an uncontrolled open-label ECG study in 26 patients, QT prolongation was observed on Day 8, independent of eribulin concentration, with no QT prolongation observed on Day 1. ECG monitoring is recommended if therapy is initiated in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid HALAVEN in patients with congenital long QT syndrome.

6 ADVERSE REACTIONS 6.1 Clinical Trials Experience The following adverse reactions are discussed in detail in other sections of the labeling: • Neutropenia • Peripheral neuropathy • QT interval prolongation The most common adverse reactions (≥25%) reported in patients receiving HALAVEN were neutropenia, anemia, asthenia/ fatigue, alopecia, peripheral neuropathy, nausea, and constipation. The most common serious adverse reactions reported in patients receiving HALAVEN were febrile neutropenia (4%) and neutropenia (2%). The most common adverse reaction resulting in discontinuation of HALAVEN was peripheral neuropathy (5%).

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.

In clinical trials, HALAVEN has been administered to 1,222 patients with multiple tumor types, including 240 patients exposed to HALAVEN for 6 months or longer. The majority of the 1,222 patients were women (82%) with a median age of 58 years (range: 26 to 91 years). The racial and ethnic distribution was Caucasian (83%), Black (5%), Asian (2%), and other (5%).

The adverse reactions described in Table 2 were identified in 750 patients treated in Study 1. In Study 1, patients were randomized (2:1) to receive either HALAVEN (1.4 mg/m2 on Days 1 and 8 of a 21-day cycle) or single agent treatment chosen by their physician (control group). A total of 503 patients received HALAVEN, and 247 patients in the control group received therapy consisting of chemotherapy [total 97% (anthracyclines 10%, capecitabine 18%, gemcitabine 19%, taxanes 15%, vinorelbine 25%, other chemotherapies 10%)] or hormonal therapy (3%). The median duration of exposure was 118 days for patients receiving HALAVEN and 63 days for patients receiving control therapy. Table 2 reports the most common adverse reactions occurring in at least 10% of patients in either group.

Table 2 Adverse Reactions with a Per-Patient Incidence of at Least 10% in Study 1 MedDRA ver 10.0 HALAVEN (n=503) Control Group (n=247) All Grades ≥ Grade 3 All Grades ≥ Grade 3 a Blood and Lymphatic System Disorders Neutropenia 82% 57% 53% 23% Anemia 58% 2% 55% 4% Nervous system disorders Peripheral neuropathyb 35% 8% 16% 2% Headache 19% <1% 12% <1% General disorders and administrative site conditions Asthenia/Fatigue 54% 10% 40% 11% Mucosal inflammation 9% 1% 10% 2% Pyrexia 21% <1% 13% <1% Gastrointestinal disorders Constipation 25% 1% 21% 1% Diarrhea 18% 0 18% 0 Nausea 35% 1% 28% 3% Vomiting 18% 1% 18% 1% Musculoskeletal and connective tissue disorders Arthralgia/Myalgia 22% <1% 12% 1% Back pain 16% 1% 7% 2% Bone pain 12% 2% 9% 2% Pain in extremity 11% 1% 10% 1% Investigations Weight decreased 21% 1% 14% <1% Metabolism and nutrition disorders Anorexia 20% 1% 13% 1% Respiratory, thoracic, and mediastinal disorders Cough 14% 0 9% 0 Dyspnea 16% 4% 13% 4% Skin and subcutaneous tissue disorders Alopecia 45% NAc 10% NAc

A focus on the Commission on cancer

Breast Cancer Collaborative Registry: Comparison of Physical and Mental Health and Sleep in Breast Cancer Survivors Constance Visovsky, PhD, RN, ACNP-BC1; Ann M. Berger, PhD, APRN, AOCNS, FAAN2; Melody Hertzog, PhD; Janique Rice, MS1; Marcia Y. Shade, MS, RN2 1 University of South Florida; 2University of Nebraska Medical Center

Purpose: Women treated for breast cancer have reported lower physical and mental health status and poorer sleep quality compared with the general female population. The Breast Cancer Collaborative Registry (BCCR) from a Midwestern tertiary medical center was used to examine these factors.

Methods: This cross-sectional design used data collected from BCCR participants at the first breast cancer diagnosis.

Descriptive statistics, correlations, t tests, and analysis of variance were used to analyze physical and mental health (ShortForm Health Survey [n = 548]), sleep quality (Pittsburgh Sleep Quality Index [n = 358]), and demographic/medical factors, and their relationships.

T:10.5"

Results: The sample was predominantly Caucasian, non-Hispanic, and living with a partner; had some postsecondary education; mean age was 58.6 years; were ≤5 years postdiagnosis; had stage I or II disease; and had received cancer treatment within the past month. Physical component scores were significantly lower and mental component scores were significantly higher in this sample compared with the general female population. Sleep-quality scores were “good” (<5) in 33% but “poor” in 66% of the sample. These primary outcomes were associated with several demographic/medical factors (age, educational level, body mass index, time since diagnosis, and performance status).

Conclusions: Several explanations are provided for this sample’s reported higher mental health scores, despite self-reports of poorer physical health and sleep quality than in the general female population.

Implications for Cancer Survivors: Results confirm the need to increase physical functioning and sleep quality in breast cancer survivors. Interventions focused in these areas may need to be tailored based on mental health and other demographic/medical factors to promote adherence in survivors.

C

Navigate

THE EVOLVING MBC LANDSCAPE...

urrently, 2.9 million women in the United States and other cancer-related symptoms and often results in a are breast cancer survivors, and this number is exdecline in QOL.7-9 Persistent bodily pain that may result 1,2 from cancer treatment has also been reported in breast canpected to increase to 3.4 million by 2015. In this paper, survivorship is defined as beginning at diagnosis.3 cer survivors. Pain can occur from multiple sources related to Survivors seek understanding of the immediate and longcancer treatment and comorbid conditions. Pain from cheterm consequences of breast cancer treatments to cure or motherapy-induced peripheral neuropathy is manifested as manage the disease, including surgery,Indication radiation, chemonumbness, tingling, and dysesthesia, and may not resolve 10 therapy, and hormonal manipulation.Halaven Women iswho redespite discontinuation of chemotherapy. indicatedcompletely for the treatment of patients with metastatic Arthralgia and joint pain resulting from at theleast use oftwo aromatase ceived treatment for breast cancer report consequences of breast cancer (MBC) who have previously received inhibitors have been reported in 36% of breast cancer survilower physical and mental health and chemotherapeutic poorer sleep quality regimens for the treatment of metastatic disease.

4,5 11 Breast cancer vors taking these medications for prevention of recurrence. compared with the general population.

Prior therapy should have included an anthracycline and a taxane survivors also report that decrements ininphysical body symptoms are reported by 10% to 64% of either and the menadjuvantUpper or metastatic setting. tal health negatively impact quality of life (QOL).6 Further women following breast cancer surgery.12 Shoulder and arm understanding of the impact of breast cancer and its treattightness, pain, numbness, swelling, and limitations in moment on physical and mental functioning and sleep quality bility have adverse effects on breast cancer survivors’ physiis important because of the impact on performance status cal, social, and emotional functioning.13-15 Please see Important Safety Information on the following Breast cancer survivors often experience a decline in and overall QOL. spread and of accompanying brief summary fullhealth in the form of prolonged stress, fear, depresmental A recent review adverse physical events experiencedofbyHalaven Prescribing Information. sion, and/or anxiety. Emotional distress in many breast survivors of various types of cancer concluded that impaired cancer survivors continues to be present, even long after physical functioning is commonly associated with fatigue HALAVEN ® is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd. © 2013 Eisai Inc. All rights reserved.

Printed in USA/November 2013 HALA0479

JONS-online.com journal of Oncology Navigation & Survivorship

29

Breast Cancer Collaborative Registry

treatment ends.16 Although depression affects 7% of the US population, the prevalence of depression is estimated to be 10% to 52% in breast cancer survivors. Elements of mental health, such as anxiety and depression, have been correlated with impaired QOL in breast cancer survivors.17,18 In a study of disease-free Finnish breast cancer survivors (n = 537), 26% of the study participants were depressed, had lower levels of QOL, and physical performance compared with the general population.19 Poor sleep quality is a prevalent symptom in women undergoing breast cancer treatment.20 Recent studies report at least 33% of breast cancer survivors have persistent sleepwake disturbances, ranking it as one of the most common and distressing symptoms.21,22 Patients with breast cancer reported the highest number (85%) of insomnia compared with patients with other types of cancers.23 Sleep-wake disturbances include problems in sleep quality, latency, efficiency, and duration; all may impact the social, mental, and physical functioning of individuals.24 Altered patterns of sleep quantity and quality have been found to continue well into the survivorship phase.25 Increased numbers of survivors have raised awareness of the urgent need to improve the treatment of the most common cancer-related symptoms.21 Interventions aimed at reducing poor sleep in survivors have resulted in improved sleep and QOL.26-28 Local, state, and national cancer agencies, and control programs have used registry data to make public health decisions and for cancer control and epidemiologic research aimed to improve patient care outcomes.29,30 Recently, registries have included factors associated with the etiology of cancer, lifestyle, and QOL. Several cancer registries provide source material for examining factors impacting QOL in patients with breast cancer.31-33 The Pathways Study, based on the Kaiser Permanente Northern California Cancer Registry of women recently diagnosed with breast cancer (n = 950), found that younger women and women presenting with late-stage disease at diagnosis reported lower QOL; women reporting higher levels of social support had better QOL, with the exception of physical well-being.34 The study of Western Australian Cancer Registry breast cancer survivors (n = 558) who were 1 to 3 years postdiagnosis indicated that physically active breast cancer survivors within a healthy weight range reported higher QOL.35 Cancer registries can address many unanswered questions and gaps concerning breast cancer survivorship. This report addresses QOL, sleep, as well as physical and mental health in breast cancer survivors. The purpose of this study was to (1) describe the Breast Cancer Collaborative Registry (BCCR) sample with regard to physical and mental health components of QOL and sleep quality, and demographic and medical characteristics; and (2) determine the

30

october 2014 â&#x20AC;˘ Volume 5, number 5

associations among physical and mental components of QOL, sleep quality, performance status, and demographic/ medical characteristics of the BCCR sample.

Methods

This cross-sectional study used data from the BCCR from a Midwestern tertiary medical center.

The BCCR database is populated with 916 cases with available data from 2008 to 2011. All data were from patient interviews that were administered upon enrollment into the registry. Enrollment took place at any phase of the cancer trajectory. For this study, only women who completed the questionnaire after their initial diagnosis were considered for inclusion (n = 692). Of these, the 548 with Short-Form Health Survey (SF-36) physical and mental component summary scores formed our sample, and 358 of those had a valid total sleep quality score from the Pittsburgh Sleep Quality Index (PSQI).

This study was approved by the Institutional Review Board. Patients provided an informed consent when they enrolled in the registry for the data to be used in clinical studies. All of the participants in the BCCR were given a questionnaire at the initial study visit. This report focuses on the initial baseline data collection due to the large sample size obtained. Follow-up data are in the process of collection.

The BCCR questionnaire was designed for standard collection of data to provide a comprehensive review of factors that could influence breast cancer survivorship. The BCCR registry was developed in collaboration with consultants with expertise in breast cancer.33 The BCCR questionnaire contains extensive categories of demographic and medical data.33 Information collected included the participantâ&#x20AC;&#x2122;s age, race, ethnicity, marital status, height and weight, highest education level, and annual income, as well as employment status. Information was obtained to ascertain physical and mental health, sleep quality, and performance status. Other pertinent medical data were collected, including current cancer diagnosis and tumor stage, cancer treatments, and menopausal status.

Physical and mental health components were measured using the SF-36 v2 Health Survey. The SF-36 measures 8 aspects of physical and mental health limitations, including physical function, role physical, role emotional, social functioning, bodily pain, mental health, vitality, and general health. Two summary component scores were calculated, one for physical and one for mental health.30 The participants were asked to respond to the items based on the past 4 weeks (standard form). Eight subscale scores were obtained by summing items indicating the extent of limitations. Normative data are reported by gender. The SF-36 has been used in over 2000 studies, and the reliability and

AONNonline.org

We Will

exhaust all possibilities.

We will…because patients are our priority.

Celgene Patient Support ® provides free and personalized assistance with patients’ access and reimbursement needs.

With continual communication and consistent follow-through, your dedicated Celgene Patient Support ® Specialist will streamline access to Celgene products by helping you and your patients with: • Benefits investigation

To Contact Celgene Patient Support®:

• Prior authorization

Call: 1-800-931-8691

• Appeal support

E-mail: patientsupport@celgene.com

• Medicare

Fax: 1-800-822-2496

• Co-pay assistance – Celgene Commercial Co-pay Program – Co-pay assistance through third-party organizations

Visit: www.CelgenePatientSupport.com Monday through Friday, 8:00 am to 7:00 pm ET

• Prescription status • Celgene free medication program • Celgene products and restricted distribution programs 4 out of 5 patients who requested assistance from Celgene Patient Support ® received their medication.

Celgene Patient Support® is a registered trademark of Celgene Corporation. © 2013 Celgene Corporation 09/13 US-CELG110059(1)

Breast Cancer Collaborative Registry

emographic/Medical Descriptive Data on Sample Table 1 D (N = 548) Variable

Mean (%)

Age, years

58.58 (28-87)

BMI, kg/m (baseline) ≤29.9 (n) ≥30 (n) 2

28.6 (16.09-54.97) 343 (62.6) 185 (33.8)

Ethnicity Hispanic Non-Hispanic

12 (2.2) 504 (92.0)

Race Caucasian Non-Caucasian

507 (92.5) 41 (7.5)

Marital status Partnered Nonpartnered

402 (73.4) 145 (26.5)

Education Up to high school Some college BA or higher

128 (23.4) 191 (34.9) 201 (36.7)

Household income <$45,000 ≥$45,000

193 (35.2) 319 (58.2)

Tobacco habit Never smoker Current smoker Former smoker

320 (58.4) 52 (9.5) 170 (31.0)

Alcohol habit Never drink Current drinker Former drinker

148 (27.0) 313 (57.1) 82 (15.0)

Performance status Fully active Restricted in strenuous activity Can walk and take care of self Need some help taking care of self

387 (70.6) 126 (23.0) 24 (4.4) 5 (0.9)

Menopausal status Premenopausal Postmenopausal

164 (29.9) 384 (70.1)

Time since first diagnosis (years) <1 1-5 >5 and <10 >10

320 (58.4) 146 (26.6) 53 (9.7) 29 (5.3)

Types of therapy received in the past month Oral therapy Immunotherapy Chemotherapy Radiation

168 (30.7) 12 (2.2) 182 (33.2) 147 (26.8)

Not all figures add up to 100% due to random missing data.

BMI indicates body mass index.

32

october 2014 • Volume 5, number 5

validity of the SF-36 are well established. Reliability scores for the 8 subscales typically exceed .80 and ranged from .80 to .95 in this sample. Version 2.0, introduced in 1996, improved the 2 role-function scales and simplified instructions and questions, thus providing greater comparability with the widely used translated and cultural adaptations.30 Sleep quality during the previous month was measured by the PSQI, a 19-item subjective tool. The total score includes 7 components: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, sleeping medication use, and daytime dysfunction. Components are scored on a 0 to 3 scale, then combined with equal weights to yield a global score ranging from 0 to 21.

Higher scores indicate more severe complaints and poorer sleep quality. The PSQI takes less than 10 minutes to complete. Cronbach’s alpha for the global PSQI has been reported as .80 and was .72 in this study. A global PSQI score ≥5 has a sensitivity of 89.6% and a specificity of 86.5% in identifying poor sleepers. Questions 10 and 11 (optional) that were to be filled out by a bed partner or roommate were not included.29 Performance status was measured using an adaptation of the Eastern Cooperative Oncology Group instrument to assess how the cancer experience affects daily activities.36 One item in the BCCR questionnaire asked participants to rate their level of physical activity over the past week. Response options were ranked from 1 to 5 and were coded as follows: (1) fully active (able to perform all activities without restriction); (2) restricted in strenuous activity (can walk, able to carry out light housework); (3) can walk and take care of self (up more than 1/2 day); (4) need some help taking care of self (spend more than 1/2 day in bed or chair); and (5) cannot take care of self at all (spend all of the time in bed/chair). Based on the authors’ data, because less than 5% of the sample reported restrictions greater than option 2, categories 2 through 5 were merged and the category was labeled as “some restrictions.”

The data were entered and verified by 3 research assistants who received training in the BCCR database. Descriptive statistics (frequency distributions or means and standard deviations) were obtained for demographic and medical variables, physical and mental health, sleep quality, and performance status. Sample means for the SF-36 subscales and component scores were compared with women in the population norming sample using a 2-sided single-sample z test.37 Correlations were calculated for the SF-36 physical health component scores, mental health component scores, and PSQI total scores. For categorical background variables, t tests or one-way analysis of variance (ANOVA) were conducted to compare category means on sleep and the SF-36 component scores. All tests was conducted using α = .05, unless otherwise noted.

AONNonline.org

A focus on the Commission on cancer

Results

Demographic and medical characteristics of the sample are displayed in Table 1. The sample was predominantly Caucasian, non-Hispanic, living with a partner, with at least some postsecondary education, and an annual household income at or exceeding $45,000. The mean age was 58.6 years, and approximately two-thirds of the sample self-reported being postmenopausal. Three-fourths of the sample were within 5 years of a breast cancer diagnosis. Pathology reports indicated the majority of the sample had stage I or stage II tumors. Most of the sample had received at least 1 form of cancer treatment within the past month; chemotherapy and oral therapy were the most common treatments.

Mean SF-36 subscale scores for the physical functioning, role physical, and bodily pain subscales, and also the mean physical component summary score were significantly lower for this sample compared with the general population (Table 2). However, this sample rated their general health status higher than the general population. Older age, lower education level, higher body mass index (BMI), having some restrictions in performance status, and poor sleep quality were all significantly associated with lower physical component summary scores (Table 3). Approximately 70% of the sample reported their performance status as being fully active, performing usual activities without restriction. The remaining 30% required assistance, with some restrictions in performance. Performance status was associated with both physical and mental component scores and sleep quality.

With respect to mean SF-36 mental subscale scores, the sample means for the role emotional and social functioning subscales were significantly lower, while the mental and vitality subscales were higher than in the general female population (Table 2). Younger age, higher BMI, fewer months since diagnosis, having some restrictions in performance status, and poor sleep quality were significantly associated with lower mental component scores (Table 3).

The t tests revealed that higher BMI, some restrictions in performance status, chemotherapy treatment within the past month, and <1 year from diagnosis were factors that were significantly associated with lower mental health component scores (Table 4).

Of the 358 patients with a PSQI total score, approximately 33% reported good sleep quality (<5). However, 66% reported poor sleep quality (≥5), and in more than half of those cases, the PSQI score was >8, a cutoff score reflective of poor sleep in patients with cancer.38 Poorer sleep quality was associated with a higher BMI, some restrictions in performance status, and lower physical and mental component scores. The t tests and ANOVA revealed that higher BMI (P = .002), some restrictions in performance status (P = .001), and some postsecondary education (P = .021) were

Mean (SD) of SF-36 Subscales and Component Scores in Table 2 BCCR Sample (N = 548) and US Female Population (N = 4032)29 0-100 scaling mean (SD)

Norm-based scores,a mean (SD)

Population, mean (SD)

Physical function

74.3 (25.4)

46.2 (10.7)b,c

48.7 (10.5)

Role physical

71.0 (29.6)

45.5 (11.6)b,c

49.0 (10.3)

Role emotional

83.4 (23.4)

48.1 (10.9)

48.9 (10.5)

Social functioning

77.7 (25.3)

47.1 (11.1)

49.0 (10.5)

Body pain

65.9 (24.4)

45.5 (10.7)b,c

49.1 (10.2)

Mental

77.0 (16.6)

51.1 (9.3)

48.8 (10.4)

Vitality

58.2 (20.8)

50.0 (10.4)

48.7 (10.1)

General health

70.9 (19.9)

50.0 (9.5)b,c

49.3 (10.2)

Physical component score

b,c

46.2 (10.6)

49.1 (10.4)

Mental component score

50.6 (10.4)b,c

48.9 (10.6)

b,c

b,c b,c

Norm-based scores have a mean of 50 and an SD of 10 in the norming sample (combined male and female). b All sample means significantly different (α = .05) from population means using a 2-sided single-sample z test. c P <.05.

SD indicates standard deviation; SF-36, Short Form Health Survey; BCCR, Breast Cancer Collaborative Registry. a

Correlation of Demographic/Medical Variables with Table 3 Sleep Quality and with SF-36 Physical and Mental Component Scores Demographic/medical

Physical

Mental

Sleep –.060

Current age

–.203

.207

Education level

.190a

.036

Body mass index

–.320

–.104

.164a

Performance status

.662a

.196a

–.201a

Months since diagnosis

.034

.132

–.002

Sleep

a

a

a

.001 a

a

–.197

–.398

—

—

.030

—

—

—

—

a

Physical Mental

a

Sleep quality measured with the PSQI ; Physical and Mental Component Scores measured by the MOS SF-36 v2.29 Sample size ranged from 345 to 358 for correlations involving PSQI and 528 to 548 for those involving SF-36. a P <.05.

SF-36 indicates Short-Form Health Survey; PSQI, Pittsburgh Sleep Quality Index.

28

significantly associated with poorer sleep quality. ANOVA revealed perceived sleep quality varied by education level.

Post hoc comparisons showed that survivors with some postsecondary education reported poorer sleep than those with a high school education or less (P = .015).

JONS-online.com journal of Oncology Navigation & Survivorship

33

Breast Cancer Collaborative Registry

Table 4 Short-Form Health Survey (SF-36) Physical and Mental Component Score Comparisons

Body mass index <29.9 ≥30 Performance status Some restrictions Fully active Chemotherapy in last month No Yes Living with partner No Yes Education levela ≤High school Some postsecondary ≥BAa Years since diagnosis <1 1-5 >5 and <10 ≥10

n

Physical component, mean (SD)

343

48.3 (9.5)

185

42.4 (11.2)

Test statistic (P)

Mental component, mean (SD)

t = 6.30 (<.001)

Test statistic (P) t = 2.68 (.008)

51.5 (10.1) 49.0 (10.6) t = 19.39 (<.001)

t = –4.23 (<.001)

155

35.2 (8.7)

47.4 (11.9)

387

50.6 (7.6)

51.9 (9.5)

366

47.0 (10.5)

182

44.8 (10.5)

t = 2.30 (.022)

t = 2.64 (.009) 51.4 (10.7) 49.0 (9.7)

t = –1.73 (.085)

t = –.68 (.498)

145

44.9 (10.5)

50.1 (10.4)

402

46.7 (10.5)

50.8 (10.4)

128

43.8 (10.6)

43.8 (10.6)

191

45.1 (10.9)

45.1 (10.9)

201

48.7 (9.8)

F = 10.41 (<.001)

F = 1.82 (.163)

F = 1.30 (.273)

F = 6.07 (<.001)

320

45.7 (10.5)

49.1 (11.0)

146

46.4 (11.2)

52.1 (9.7)

53

48.8 (9.0)

53.7 (8.2)

29

46.6 (10.1)

54.2 (7.0)

≥BA was significantly different from both ≤high school and some postsecondary education in post hoc comparisons using Bonferroni correction.

SD indicates standard deviation.

a

Discussion

This cancer registry study examined the physical and mental health components of QOL, sleep quality, and demographic and medical characteristics of breast cancer survivors, and the associations among these variables. A major finding consistent with previous reports in the literature was that these breast cancer survivors reported lower overall physical functioning. Although the majority of the survivors rated themselves as fully physically active on a gross measure of performance status, a more sensitive measure indicated lower physical functioning than the general population. Sleep quality was poor for the majority of survivors in this sample, a finding consistent in patients with breast cancer, especially while they are actively receiving treatment. A major finding that was not consistent with previous studies was that this sample of survivors reported higher mental health scores than in the general female population. These findings will be discussed, strengths and weaknesses identified, and implications proposed.

34

october 2014 • Volume 5, number 5

Physical Health

Based on the authors’ observations, lower physical functioning was prevalent in this sample, most of whom were in the first year following diagnosis. The lower physical component score is congruent with published literature.The lower scores for several physical subscales are consistent with other studies of cancer survivors.39,40 This registry study confirmed previous findings that the impact on physical functioning is more severe in women undergoing chemotherapy4 compared with women receiving other cancer treatments.9 Other studies consistently report significant declines in physical functioning in the first 5 years following a breast cancer diagnosis, which dissipate with further elapsed time.31,41 However, physical functioning in this sample was not higher in survivors who were ≥10 years postdiagnosis, perhaps due to comorbid diseases and aging. Though differences were not significant, the pattern of means is consistent with descriptive study reports of higher physical functioning in the 5- to 10-year posttreatment phase.42,43

AONNonline.org

Breast Cancer Collaborative Registry

The present study agrees with previous reports of bodily pain in women who received breast cancer treatment.10-15 However, this study was not able to determine the exact source of respondentsâ&#x20AC;&#x2122; pain. Breast cancer survivors who are overweight or obese have reported higher pain levels compared with normal weight survivors.42,43 One-third of the BCCR participants were classified as obese, and obesity may be one potential contributor to the bodily pain reported by this sample. This study also supports a relationship between higher education level and higher physical functioning in the general population.9

Mental Health

Although some of the SF-36 subscale scores were lower in this sample than in the general population, the mental component scores were higher. This studyâ&#x20AC;&#x2122;s findings contradict previous reports of lower mental health scores in breast cancer survivors, frequently reported as emotional distress, anxiety, and depression.16,17,25 Several studies found the SF-36 mental component scores of breast cancer survivors to be higher after chemotherapy ended.44,45,46 However, a study from France reported no association between treatment type and mental component scores in long-term breast cancer survivors.47 These findings may be explained by the demographic characteristics of the BCCR sample. The sample was drawn from an urban cancer center in the Midwest that patients from surrounding rural communities, a demographic area with reported higher mental health scores in the general population. Other factors such as the relatively higher age (mean, 58.5 years), education level, household income, partnered status, and performance status may also have affected this result and may account for the higher mental health scores reported in this sample.

Several demographic variables were associated with poorer mental health in this sample. Higher BMI has been associated with lower mental health scores after the chemotherapy treatments end.48 Consistent with the literature, survivors with less time since diagnosis had poorer mental health, with this relationship reported as persisting 5 to 10 years postdiagnosis.31 The literature is inconsistent regarding the association between age and mental health in breast cancer survivors.

In Latina survivors, older age has been associated with poorer mental health.48 This study found poorer mental health in younger, primarily Caucasian women. Younger age has been associated with increased depressive symptoms49 and a more negative impact on psychosocial functioning.49,50 This finding may be related to differences in partner relationships, body image, sexual functioning, and coping mechanisms in younger women with breast cancer.46 Previous research supports feelings of negative family

36

october 2014 â&#x20AC;˘ Volume 5, number 5

impact, career disruption, and anxiety due to the potentially more severe illness that is often present in younger women with breast cancer.51,52

Sleep Quality

Most women have reported a high number of night time awakenings during and after breast cancer treatment.53 Studies have confirmed that changes in sustained sleep after breast cancer diagnosis are related to the degree and duration of other cancer-related symptoms such as fatigue, distress, depression, low physical activity levels, and lower QOL.25,51,54 The findings from this study further support that poor sleep quality is associated with poorer physical and mental health. The associations between poor sleep quality, higher BMI, and lower performance status were consistent with current literature.55 Results regarding poorer sleep after breast cancer diagnosis in women with some postsecondary education contradict literature associating higher risk of poor sleep in women with less education. The factors that may underlie poor sleep in this sample cannot be determined by the registry data. However, early identification of poor sleep quality among women with breast cancer who have a higher BMI, restricted physical performance, and poor mental health can assist the nurse navigator in preventing further decrements in physical and mental health that can persist well into survivorship.

Breast Cancer Registry

Cancer registries can be useful in uncovering short- and long-term issues related to breast cancer survivorship, specifically for physical and mental health and overall QOL. At present, few studies use population-based cancer registries for advancing knowledge of breast cancer survivorship. The majority of registry studies have used a cross-sectional design and thus lack generalizability. Findings from the BCCR support the findings of 2 other population-based cancer registries that suggest physical functioning impairments occur with breast cancer treatments and these impairments are influenced by aging.31,48 However, 1 registry study52 found younger women had better well-being but worse overall QOL. These participants were recruited and measures taken in the immediate postdiagnosis period. In contrast, the BCCR study enrolled participants in all phases of the cancer survivorship trajectory. In another registry study, physically active breast cancer survivors with a normal BMI reported higher QOL.35 Strengths of this study include the large sample and inclusion of a measurement of sleep quality. The large number of breast cancer registry participants provided additional insights into survivorship issues associated with recovery from breast cancer treatment. Sleep quality can affect QOL, but its measurement is generally not included in

AONNonline.org

A focus on the Commission on cancer

cancer registries. Several limitations to this report have been identified. These include the cross-sectional design and a high percentage of early-phase breast cancer survivors. The measure of performance status was a single-item question that addressed “activity levels” only and thus provided limited data. The SF-36 measurement did not permit us to determine the reason for bodily pain present in this sample of breast cancer survivors.

Population-based cancer registries provide an opportunity for nurse researchers to examine important clinical, demographic, and individual variables in order to further understand how these factors impact breast cancer survivorship.

Implications for future research include understanding the individual factors that may negatively impact survivorship and recognizing the need to develop interventions to improve physical function in all survivors, and specifically for those who enter treatment with a higher BMI, poor sleep, and lower performance status. Implications for practice for the nurse navigator include assessment and monitoring of physical and mental health, sleep disturbances, and other symptoms from the time of diagnosis, during treatment, and throughout survivorship. Nurse navigators are in a pivotal position to address individual patient factors that may impact QOL in breast cancer survivors. Patients with persistent pain, depression, anxiety, younger age, higher BMI, and poor sleep who are newly diagnosed and have some restrictions in performance status are at risk for poor QOL. Nurse navigators should recommend that clinical care for sleep disturbances and physical and mental health issues be provided promptly to enhance QOL among women with breast cancer. Furthermore, breast cancer survivorship programs should be initiated early and tailored to the breast cancer survivor’s individual needs. It is particularly impor­ tant to address the needs of patients most at risk for poor sleep quality, which can lead to decrements in physical and mental health and impaired overall QOL. g Acknowledgments: Kenneth Cowan, MD, PhD; Simon Sherman, PhD; and Elizabeth Fleissner, BS, RN. Author Disclosure Statement: All authors have nothing to disclose.

Corresponding Author: Constance Visovsky, PhD, RN, ACNP-­ BC, University of South Florida, 12901 Bruce B. Downs Blvd, MDC 22, Tampa, FL 33612-4766. E-mail: cvisovsk @ health.usf.edu.

References

1. American Cancer Society. Cancer Facts & Figures 2013. www.cancer.org/ research/cancerfactsfigures/cancerfactsfigures/cancer-facts-figures-2013. Accessed May 5, 2014.

2. Ellsworth RE, Valente AL, Shriver CD, Bittman B, Ellsworth DL. Impact

of lifestyle factors on prognosis among breast cancer survivors in the USA. Expert Rev Pharmacoecon Outcomes Res. 2012;12(4):451-464. doi:10.1586/ erp.12.37.

3. Nevidjon B. Evolution of survivorship care. In: Lester JL, Schmitt P, eds.

Cancer Rehabilitation and Survivorship: Transdisciplinary Approaches to Personalized Care. Pittsburgh, PA: Oncology Nursing Society; 2011:1-2.

4. Berger AM, Lockhart K, Agrawal S. Variability of patterns of fatigue and quality of life over time based on different breast cancer adjuvant chemotherapy regimens. Oncol Nurs Forum. 2009;36(5):563-570.

5. Huang SM, Tai CJ, Lin KC, Tai CJ, Tseng LM, Chien LY. A comparative study of symptoms and quality of life among patients with breast cancer receiving target, chemotherapy, or combined therapy. Cancer Nurs. 2013;36(4): 317-325.

6. Smith AW, Alfano CM, Reeve BB, et al. Race/ethnicity, physical activity, and quality of life in breast cancer survivors. Cancer Epidemiol Biomarkers Prev.

2009;18(2):656-663.

7. Brearley SG, Stamataki Z, Addington-Hall J, et al. The physical and practical problems experienced by cancer survivors: a rapid review and synthesis of the literature. Eur J Oncol Nurse. 2011;15(3):204-212.

8. Cheville AL, Troxel AB, Basford JR, Kornblith AB. Prevalence and treatment patterns of physical impairments in patients with metastatic breast cancer. J Clin Oncol. 2008;26(16):2621-2629.

9. Sehl ME, Satariano WA, Ragland DR, Reuben DB, Naeim A. Attribution of functional limitation to cancer decreases in the year following breast cancer diagnosis in older patients. Crit Rev Oncol Hematology. 2009;71(1):62-69.

10. Stubblefield MD, McNeely ML, Alfano CM, Mayer DK. A prospective surveillance model for physical rehabilitation of women with breast cancer: chemotherapy-induced peripheral neuropathy. Cancer. 2012;118(suppl 8): 2250-2260.

11. Niravath P. Aromatase inhibitor-induced arthralgia: a review. Ann Oncol.

2013;24(6):1443-1449. doi:10.1093/annonc/mdt037. Epub 2013 Mar 6.

12. Hayes SC, Johansson K, Stout NL, et al. Upper-body morbidity after breast cancer: incidence and evidence for evaluation, prevention, and management within a prospective surveillance model of care. Cancer. 2012;118 (suppl 8):2237-2249.

13. Hayes SC, Rye S, Battistutta D, DiSipio T, Newman B. Upper-body morbidity following breast cancer treatment is common, may persist longer-term and adversely influences quality of life. Health Qual Life Outcomes.

2010;8:92.

14. Kärki A, Simonen R, Mälkiä E, Selfe J. Impairments, activity limitations and participation restrictions 6 and 12 months after breast cancer operation.

J Rehabil Med. 2005;37(3):180-188.

15. Kwan W, Jackson J, Weir LM, Dingee C, McGregor G, Olivotto IA. Chronic arm morbidity after curative breast cancer treatment: prevalence and impact on quality of life. J Clin Oncol. 2002;20(20):4242-4248.

16. Deshields T, Tibbs T, Fan MY, Taylor M. Differences in patterns of depression after treatment for breast cancer. Psychooncology. 2006;15(5):398-406.

17. Zainal N Z, Nik-Jaafar N R, Baharudin A, Sabki ZA, Ng C. Prevalence of depression in breast cancer survivors: a systematic review of observational studies. Asian Pac J Cancer Prev. 2013;14(4):2649-2656. doi:http://dx.doi. org/10.7314/APJCP.2013.14.4.2649.

18. Mishra SI, Scherer RW, Geigle PM, et al. Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database Syst Rev. 2012;8/CD007566.

19. Penttinen H M, Saarto T, Kellokumpu-Lehtinen P, et al. Quality of life and physical performance and activity of breast cancer patients after adjuvant treatments. Psychooncology. 2011;20(11):1211-1220. doi:10.1002/pon.1837.

Epub 2010 Sep 27.

20. Dodd MJ, Cho MH, Cooper BA, Miaskowski C. The effect of symptom clusters on functional status and quality of life in women with breast cancer.

Eur J Oncol Nurs. 2010;14(2):101-110.

21. Bower JE. Behavioral symptoms in patients with breast cancer and survivors. J Clin Oncol. 2008;26(5):768-777.

22. Roscoe JA, Kaufman ME, Matteson-Rusby SE, et al. Cancer-related fatigue and sleep disorders. Oncologist. 2007;12(suppl 1):35-42.

23. Palesh OG, Roscoe JA, Mustian KM, at al. Prevalence, demographics, and psychological associations of sleep disruption in patients with cancer: University of Rochester Cancer Center—Community Clinical Oncology Program. J Clin Oncol. 2010;28(2):292-298.

JONS-online.com journal of Oncology Navigation & Survivorship

37

Breast Cancer Collaborative Registry

24. Alfano CM, Lichstein KL, Vander Wal GS, et al. Sleep duration change across breast cancer survivorship: associations with symptoms and health-­ related quality of life. Breast Cancer Res Treat. 2011;130(1):243-254.

25. Fortner BV, Stepanski EJ, Wang SC, Kasprowicz S, Durrence HH. Sleep and quality of life in breast cancer patients. J Pain Symptom Manage. 2002;24 (5):471-480.

26. Espie CA, Fleming L, Cassidy J, et al. Randomized controlled clinical effectiveness trial of cognitive behavior therapy compared with treatment as usual for persistent insomnia in patients with cancer [published correction appears in J Clin Oncol. 2010;28(19):3205]. J Clin Oncol. 2008;26(28):4651-4658.

27. Savard J, Simard S, Ivers H, Morin CM. Randomized study on the efficacy of cognitive-behavioral therapy for insomnia secondary to breast cancer, part I: sleep and psychological effects. J Clin Oncol. 2005;23(25):6083-6096.

28. Langford DJ, Lee K, Miaskowski C. Sleep disturbance interventions in oncology patients and family caregivers: a comprehensive review and metaanalysis. Sleep Med Rev. 2012;16(5):397-414.

29. Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193-213.

30. Ware JE Jr. SF-36 health survey update. Spine. 2000;25(24):3130-3139.

31. Klein D, Mercier M, Abeilard E, et al. Long-term quality of life after breast cancer: a French registry-based controlled study. Breast Cancer Res Treat. 2011;129(1):125-134.

32. Martino M, Ballestrero A, Zambelli A, et al. Long-term survival in patients with metastatic breast cancer receiving intensified chemotherapy and stem cell rescue: data from the Italian registry. Bone Marrow Transplant. 2013; 48(3):414-418.

33. Sherman S, Shats O, Fleissner E, et al. Multicenter breast cancer collaborative registry. Cancer Inform. 2011;10:217-226.

34. Kwan ML, Ergas IJ, Somkin CP, et al. Quality of life among women recently diagnosed with invasive breast cancer: the Pathways Study. Breast Cancer Res Treat. 2010;123(2):507-524.

35. Milne HM, Gordon S, Guilfoyle A, Wallman KE, Courneya KS. Association between physical activity and quality of life among Western Australian breast cancer survivors. Psychooncology. 2007;16(12):1059-1068.

36. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6): 649-655.

37. Ware JE, Kosinski M, Dewey JE. How to Score Version 2 of the SF-36 Health Survey. Lincoln, RI: QualityMetric Inc; 2000.

38. Carpenter JS, Andrykowski MA. Psychometric evaluation of the Pittsburgh Sleep Quality Index. J Psychosom Res. 1998;45(1):5-13.

39. Zhao G, Li C, Li J, Balluz LS. Physical activity, psychological distress, and receipt of mental healthcare services among cancer survivors. J Cancer Surviv.

2013;7(1):131-139.

40. Maly RC, Stein JA, Umezawa Y, Leake B, Anglin MD. Racial/ethnic

differences in breast cancer outcomes among older patients: effects of physician communication and patient empowerment. Health Psychol. 2008;27(6): 728-736. doi:10.1037/0278-6133.27.6.728.

41. Casso D, Buist DS, Taplin S. Quality of life of 5-10 year breast cancer survivors diagnosed between age 40 and 49. Health Qual Life Outcomes. 2004;2:25.

42. Ganz PA. Quality of life assessment in breast cancer: when does it add prognostic value for survival? [editorial] Breast J. 2011;17(6):569-570.

43. Keating NL, Nørredam M, Landrum MB, Huskamp HA, Meara E. Physical and mental health status of older long-term cancer survivors. J Am Geriatr Soc. 2005;53(12):2145-2152.

44. Forsythe LP, Alfano CM, George SM, et al. Pain in long-term breast cancer survivors: the role of mass index, physical activity, and sedentary behavior. Breast Cancer Res Treat. 2013;137(2):617-630.

45. Ganz PA, Kwan L, Stanton AL, Bower JE, Belin TR. Physical and psychosocial recovery in the year after primary treatment of breast cancer. J Clin Oncol.

2011;29(9):1101-1109. doi:10.1200/JCO.2010.28.8043. Epub 2011 Feb 7.

46. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(5):386-405. doi: 10.1093/jnci/djr541. Epub 2012 Jan 23.

47. Tessier P, Lelorain S, Bonnaud-Antignac A. A comparison of the clinical determinants of health-related quality of life and subjective well-being in longterm breast cancer survivors. Eur J Cancer Care (Engl). 2012;21(5):692-700.

48. Azuero A, Benz R, McNees P, Meneses K. Co-morbidity and predictors of health status in older rural breast cancer survivors. Springerplus. 2014;3:102. doi:10.1186/2193-1801-3-102. eCollection 2014.

49. Broeckel JA, Jacobsen PB, Balducci L, Horton J, Lyman GH. Quality of life after adjuvant chemotherapy for breast cancer. Breast Cancer Res Treat.

2000;62(2):141-150.

50. Avis NE, Crawford S, Manuel J. Psychosocial problems among younger women with breast cancer. Psychooncology. 2004;13(5):295-308.

51. Bloom JR, Stewart SL, Chang S, Banks PJ. Then and now: quality of life of young breast cancer survivors. Psychooncology. 2004;13(3):147-160.

52. Costanzo ES, Lutgendorf SK, Mattes ML, et al. Adjusting to life after treatment: distress and quality of life following treatment for breast cancer. Br J Cancer. 2007;97(12):1625-1631.

53. Dhruva A, Paul SM, Cooper BA, et al. A longitudinal study of measures of objective and subjective sleep disturbance in patients with breast cancer before, during, and after radiation therapy. J Pain Symptom Manage. 2012; 44(2):215-228.

54. Otte JL, Carpenter JS, Russell KM, Bigatti S, Champion VL. Prevalence, severity, and correlates of sleep-wake disturbances in long-term breast cancer survivors. J Pain Symptom Manage. 2010;39(3):535-547.

55. Payne J, Piper B, Rabinowitz I, Zimmerman B. Biomarkers, fatigue, sleep, and depressive symptoms in women with breast cancer: a pilot study. Oncol Nurs Forum. 2006;33(4):775-783.

Who Will Be the ONE?

The Oncology Nurse Excellence Award Winner The Oncology Nurse-APN/PA® (TON ) is pleased to announce the 2014 ONE (Oncology Nurse Excellence) Award. This annual award recognizes an oncology nurse for outstanding contribution to oncology nursing practice, patient care, or education in 2014.

The 4 leading nominees will be profiled online and in the August issues of TON and the Journal of Oncology Navigation & Survivorship ® (JONS). Readers will have an opportunity to nominate an individual online through June 2, 2014, and the winner will be announced at the Fifth Annual Academy of Oncology Nurse & Patient Navigators (AONN+) Conference, September 18-21, 2014, in Orlando, Florida, and profiled in the December issues of TON and JONS. The winner will also receive a plaque recognizing their contribution to oncology nursing, as well as a donation made to the charity of their choice in their name.

Nominate a nurse at TheOncologyNurse.com/one-award

38

october 2014 • Volume 5, number 5

TONONEAwardFill_33114

AONNonline.org

Now enrolling: MURANO study Investigating the Selective BCL-2 Inhibitor GDC-0199/ABT-199 in Chronic Lymphocytic Leukemia GDC-0199/ABT-199 is an investigational agent that has not been approved by regulatory agencies.

A Phase III Study of GDC-0199/ABT-199 Plus Rituximab Compared With Bendamustine Plus Rituximab in Patients With Relapsed or Resistant Chronic Lymphocytic Leukemia (CLL)

GDC-0199/ABT-199 + rituximab

Phase III Relapsed or resistant CLL (N=370)

GDC-0199/ABT-199 continued for 2 years or until disease progression

Bendamustine + rituximab Randomize Primary Endpoint

Secondary Endpoints

• Investigator-assessed progression-free survival, defined as time from randomization until disease progression or death from any cause

• Overall response rate • Incidence of adverse events

Key Inclusion Criteria

Key Exclusion Criteria

• Adult patients ≥18 years of age • Diagnosis of CLL per diagnostic criteria and relapsed or refractory CLL per the iwCLL guidelines • Previously treated with 1-3 lines of therapy (eg, completed ≥2 treatment cycles per therapy), including ≥1 standard chemotherapy-containing regimen • Previously treated with bendamustine, only if duration of response was ≥24 months • ECOG performance status of 0-1 • Adequate bone marrow function • Adequate renal and hepatic function

• Transformation of CLL to aggressive non-Hodgkin lymphoma or CNS involvement by CLL • Undergone an allogenic stem-cell transplant • A history of significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease • Hepatitis B, hepatitis C, or known HIV-positive • Receiving warfarin treatment • Received an anti-CLL monoclonal antibody within 8 weeks prior to the first dose of study drug • Received any anticancer or investigational therapy within 14 days prior to the first dose of study drug or has not recovered from previous therapy • Received CYP3A4 inhibitors (such as fluconazole, ketoconazole and clarithromycin) or inducers (such as rifampin, carbamezapine, phenytoin, St John’s Wort) within 7 days prior to the first dose of GDC-0199/ABT-199 • Prior GDC-0199/ABT-199 treatment

To learn more about this study, please visit www.ClinicalTrials.gov (NCT02005471, GO28667) or call the Trial Information Support Line at 1-888-662-6728.

GDC-0199/ABT-199 is being codeveloped by AbbVie and Genentech, a member of the Roche Group.

© 2014 Genentech USA, Inc. All rights reserved. BIO0002506000 Printed in USA.

Reference: ClinicalTrials.gov, as of 5/2014.

A2396579

THE PATIENT’S VOICE

Practice Makes Not Perfect: Striving After Cancer Carolyn Comeau

A

s a 7-year breast cancer survivor, my primary feeling most of the time is awe and gratitude that I’m still here. I can savor life’s small moments and big events, from sipping a piping hot tall dark roast to celebrating my dear friend’s 50th by dancing my you-know-what off!

There’s a phenomenon I’ve spoken about with other survivors, however, that also often accompanies survivorship and can at times be vexing. It’s similar to something I’ve dubbed the “What Did You Do to Get Cancer Syndrome” (WDYDGCS), which occurs when one is first diagnosed. My main topic is its sequel, “Perfect Survivor Syndrome,” or PSS, but in order to talk about that, I have to first familiarize you with WDYDGCS. When I was first diagnosed, I received an outpouring of love and support from close friends, family, acquaintances, and strangers alike, but with some, there also came a dose of questioning about how I lived prior to my getting cancer. I was peppered with questions about my precancer lifestyle, some quite personal. “Did you eat much (fill in your ingestible villain of choice: meat, sugar, carbohydrates, dairy, processed foods, coffee) before your diagnosis?” “What about exercise?” they’d ask quizzically, proceeding to whether the water I drank was filtered properly, if I had a microwave, if I thought positively at least 90% of the time, or if I wore the

I feel that our culture is a bit obsessed with control, and if you throw cancer into the mix, it really gets interesting. color purple too much (well, maybe the purple part is a bit of an exaggeration, but it certainly felt like it got to that level of minute detail). It was when a woman approached me one day and quietly said, “You know, don’t you, that mammograms are what give you breast cancer?” that I (figuratively at least) threw my arms up in the air and decided I’d need to make the decisions that were best for me, from that point on.

I’m well aware of how loaded with controversy the previous paragraph is. I don’t intend to start a debate or foster dispute. These are solely my views, and I don’t pretend to speak for all breast cancer survivors. I just write this in the hope that it puts some readers’ minds at ease—that they forgive themselves more easily for the harsh judgments we make about everything we do and don’t do after diagnosis.

40

october 2014 • Volume 5, number 5

As for the answers to those questions, the fact is I’d been a vegetarian for 15 years of my adult life; paid attention to nutrition and ate a balanced diet; wasn’t officially a jock, but was certainly active every day; and as for my attitude, I’ve been described by some as not only energetic but even the dreaded “perky!”

I realized at some point that I’d probably committed this same faux pas, at least inwardly, with people before, so I’m not guiltless.

The conclusion I’ve come to is that most people (including me) are downright terrified when confronted with the C-word. And why not? It’s the stuff of scary statistics and stories, and the word is usually accompanied by sobering phrases like “valiantly fighting,” “enduring lots of treatment,” and the worst one, to me, “succumbed to cancer.”

I got to the point where this line of conversation annoyed the bejesus out of me, but then I realized it came from a place of fear—a how-do-I-make-absolutely-certainI-don’t-get-cancer kind of fear. And I couldn’t blame them.

I realized these inquiries also came out of love and concern for me. Everyone feels helpless when someone they love gets diagnosed; that is why casseroles were invented!

I bring up the “What Did You Do to Get Cancer Syndrome” because its sequel, after I finished my course of treatment, was “How Do I Become the Perfect Cancer Survivor?” This practice had less to do with people advising me than with my having a raging internal debate with myself about the best practices for living optimally post cancer. To tell the truth, I spent many hours devising in my mind a rather rigid “Perfect Survivor’s Plan,” or PSP, that was impossible to live up to. It went something like this: 1. Eat some type of “ideal” diet.

2. Don’t get stressed. Retain the aura of Buddha, despite the fact that your kid has a fever, your car needs new tires, and you have an imminent work deadline.

3. Attract positivity by being 100% positive 100% of the time. Whatever you do, don’t focus on the school principal’s curt email response to your fantastic fundraising idea, the fact that your property taxes are way too high, and whether or not you should dye your hair.

4. Engage in a grueling workout regimen, often. The more punishing, the better.

5. Concentrate on each and every thing that could be a carcinogen: imbalanced pH in your body, nitrites in processed meats, free radicals, and the ever-popular Carcinogens That Aren’t Always Apparent (radon,

AONNonline.org

SCIENTIFIC CONFERENCES 2014-2015

7th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved Co-Chairpersons: Ethan Dmitrovsky, Rick A. Kittles, Electra D. Paskett, and Victoria L. Seewaldt November 9-12, 2014 • San Antonio, TX The 10th Anniversary Personalized Medicine Conference Co-Chairpersons: Raju Kucherlapati and Scott Weiss November 12-13, 2014 • Boston, MA EORTC-NCI-AACR International Symposium on Molecular Targets and Cancer Therapeutics Co-Chairpersons: Jean-Charles Soria, Lee J. Helman, and Jeffrey A. Engelman November 18-21, 2014 • Barcelona, Spain Tumor Immunology: A New Chapter Co-Chairpersons: Robert H. Vonderheide, Nina Bhardwaj, Stanley Riddell, and Cynthia L. Sears December 1-4, 2014 • Orlando, FL San Antonio Breast Cancer Symposium Co-Directors: Carlos L. Arteaga, Ismail Jatoi, and C. Kent Osborne December 9-13, 2014 • San Antonio, TX Myc: From Biology to Therapy Co-Chairpersons: James E. Bradner, Martin Eilers, Dean W. Felsher, and Carla Grandori January 7-10, 2015 • La Jolla, CA Translation of the Cancer Genome Co-Chairpersons: William C. Hahn, Lynda Chin, and William R. Sellers February 7-9, 2015 The Fairmont • San Francisco, CA Computational and Systems Biology of Cancer Co-Chairpersons: Andrea Califano, Brenda Andrews, and Peter Jackson February 8-11, 2015 The Fairmont • San Francisco, CA AACR-Society of Nuclear Medicine and Molecular Imaging Joint Conference: Molecular Imaging in Cancer Biology and Therapy Co-Chairpersons: Carolyn J. Anderson, Christopher H. Contag, and David Piwnica-Worms February 11-14, 2015 • San Diego, CA

Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers Co-Chairpersons: Rakesh K. Jain, Peter Carmeliet, Helen Chen, Harold F. Dvorak, and Napoleone Ferrara March 5-8, 2015 • Orlando, FL AACR Annual Meeting 2015 Program Committee Chairperson: Lewis C. Cantley April 18-22, 2015 • Philadelphia, PA Advances in Brain Cancer Research Co-Chairpersons: Eric C. Holland, Franziska Michor, Martine F. Roussel, and Michael D. Taylor May 27-30, 2015 • Washington, DC Metabolism and Cancer Co-Chairpersons: Ralph J. DeBerardinis, David M. Sabatini, and Almut Schultze June 7-10, 2015 • Bellevue, WA Cancer Biostatistics Workshop Director: Steven Piantadosi June 7-13, 2015 • Lake Tahoe, CA AACR Precision Medicine Series: Integrating Real-Time Genomics and Cancer Therapy Co-Chairpersons: Charles L. Sawyers, Elaine R. Mardis, and Arul M. Chinnaiyan June 13-16, 2015 • Salt Lake City, UT EACR-AACR-SIC Special Conference Special Conference on Anticancer Drug Action and Drug Resistance: From Cancer Biology to the Clinic Organizing Committee: Moshe Oren, Riccardo Dolcetti, Richard M. Marais, Daniel S. Peeper, Pasi Jänne, Alice T. Shaw, Paola Chiarugi, and Silvia Giordano June 20-23, 2015 • Florence, Italy Pediatric Oncology Co-Chairpersons: Scott Armstrong, Charles G. Mullighan, Kevin M. Shannon, and Kimberly Stegmaier November 9-12, 2015 • Fort Lauderdale, FL Developmental Biology and Cancer Co-Chairpersons: Hans Clevers, Stuart Orkin, Suzanne Baker November 30-December 3, 2015 • Boston, MA

THE PATIENT’S VOICE

pesticide residue on my celery, and second hand smoke). And then there’s the newly discovered danger in all things yellow—now I can worry about the rubber gloves I use to do the dishes, countless sippy cups my kids’ lips touched, and our current shower curtain!

Below are my admittedly slightly tongue-in-cheek, but ultimately much more realistic responses to the list above, created after many conversations with other survivors and following my own sleep-challenged nights: 1. Life’s not worth living if I’m eating only black beans and kale. Nothing against black beans and kale—I just think food is a sensual pleasure and have decided that “everything in moderation” is a rule I can actually live with.

2. I’m a cancer survivor—I get stressed! But I try to see the myriad strategies I can use to assuage my worry: meditation, walking the dog, a soothing bath, positive visualization, getting lost in a novel. The practical advantages of these prescriptions? They don’t cost a thing.

3.

I am a human being with an expansive range of human emotions, and the range includes times of being blue, anxious, and frustrated, as well as content, peaceful, and jovial. I’ve decided that it’s not a good idea for me to try to mold my feelings around a hardto-attain, idealistic model. Feelings are not only completely unique—they ought not to be judged. That’s not to say I don’t think there’s a time and place for aids like antidepressants. I don’t think we should “bootstrap it” through the cancer journey and what follows, but our emotions represent an inherently well-designed and functional continuum.

4. I will go to the Y and use the rowing machine and take Zumba classes because I also happen to enjoy those things. I will walk my dog. I may dance when I cook dinner. I will even wear a pedometer and try to reach 10,000 steps.

5. In the words of the hit song from Frozen, I’ve “let it go.” It’s not that I live in a world where I’m oblivious to risk; rather, I try to keep my worries in perspective, so that I can indeed become more Buddha-like (see #2 of the first list!). Cancer helped me figure out why I get so aggravated with conspiracy theorists. I’ve always thought I have enough to worry about without wondering if UFOs are government funded! Now, I really can differentiate what’s worth my fretting and what is unproductive agonizing.

I feel that our culture is a bit obsessed with control, and if you throw cancer into the mix, it really gets interesting.

Perhaps it’s our strong Judeo-Christian tradition in the United States, but the belief seems to persist that if we live a certain way, we get a guaranteed, favorable outcome.

One of the hardest parts about cancer for me is that it’s

42

october 2014 • Volume 5, number 5

so randomly cruel. It’s not just jerks who get cancer, and sometimes that’s how I feel it should go. Rather, it’s often wonderful, loving, smart, funny, community-minded people. It’s one thing to know something intellectually and another thing to know it emotionally. For me, cancer made me cross over the bridge into the land of knowing things emotionally, and I’m grateful. This helped me in the process of finding a happy medium when it came to defining my personal best practices for cancer survivorship.

Despite what might seem a glib, dark humor on my part, my cancer journey intensified the level of gray I decided I could live with. By this I mean I became less sure of things, and more willing to consider the fact that there are even fewer absolute answers in life than I thought.

Every person I’ve met who has coped with cancer has a very special perspective.

There is a loss of innocence that comes along with a cancer diagnosis, but there’s an undeniably enriching awakening too. Many of us are awakened to truly reassess our lives during and after treatment (from relationships, to jobs, to where we live), to reconnect with things we forgot we loved (painting, gardening, or chess), and to ask hard questions about what we’ve been doing with our time and how we really want to spend it henceforth. Our “no pain, no gain” culture can stifle this kind of prioritization. I’ve heard from more than a few survivors that their journey helped them prioritize, but quick!

Every person I’ve met who has coped with cancer has a very special perspective, and I relish hearing their list of how to live their best postdiagnosis life. Well-known developmental psychologist Bruno Bettelheim’s book A Good Enough Parent posited that parents shouldn’t strive for perfection, not only because it’s impossible but also because children would never develop resilience. I reckon that cancer patients and survivors uniformly believe they’ve developed enough resilience, but it’s undeniable that no one’s life escapes significant adversity. As we face it, we adjust our rules for living—both the simple (What should I eat?) and the more complex (With whom should I spend my time?).

Every new person I meet has lessons to teach me, and I, hopefully, can offer some as well. Each day illuminates varying levels of my success with Carolyn’s Rules of Survivorship, but cancer has also taught me to be more forgiving to my most outspoken critic: myself.

Armed with my list, each day I start anew, but now I remember to cut myself some everlovin’ slack. That’s the simplest, most deconstructed form of my “survivor-osophy” that I try my best to carry with me. g

AONNonline.org

As patient needs are changing— Pfizer’s assistance programs are changing too

Introducing Pfizer RxPathways™— our answer to changing patient needs For more than 25 years, Pfizer has offered an array of prescription assistance programs to help eligible patients get access to their Pfizer medicines. To meet the changing needs of today’s patients, we’ve consolidated these services into one comprehensive program.

Introducing Pfizer RxPathways, formerly Pfizer Helpful Answers, our remodeled patient assistance program that helps eligible patients get access to their Pfizer medicines by offering a range of support services, including insurance counseling, co-pay help,* providing Pfizer medicines for free or at a savings, and more.

Pfizer RxPathways: filling a need for prescription assistance

Visit www.PfizerRxPath.com to learn more. *This is not health insurance. Terms and conditions apply.

Pfizer RxPathways™ is a joint program of Pfizer Inc. and the Pfizer Patient Assistance Foundation.

Pfizer RxPathways™ is part of Pfizer’s Global Social Investments portfolio. For more information, please visit www.pfizer.com/responsibility.

PHA562610

©2014 Pfizer Inc.

All rights reserved.

Printed in USA/April 2014

Clinical Trial Tracker

New Clinical Trials Under Way

T

he following clinical trials are currently recruiting patients with renal cell carcinoma (RCC) for inclusion in several investigations. Each trial description includes the NLM Identifier to use as reference with ClinicalTrials.gov.

Neoadjuvant Pazopanib in RCC

The purpose of this phase 2 study is to evaluate the effect of neoadjuvant pazopanib on disease response and recurrence and to establish predictive biomarkers of drug activity in patients with histologically confirmed, localized RCC. The study will examine complete response and partial response associated with pazopanib at 8 weeks, and is expected to enroll 56 patients. Patients aged ≥18 years with nonmetastatic, clinical stage II RCC and no evidence of extranodal involvement are eligible to participate if other criteria are met.

The primary outcome for this study is response rate after 8 weeks of neoadjuvant treatment with pazopanib. Secondary outcome measures include recurrence-free survival, number of adverse events, and the impact of pazopanib on surgical approach. Study locations include New York, North Carolina, and Texas. For more information, contact Gayle Grigson, RN, at 919-966-4432 or gayle_grigson@med. unc.edu, or Donna Rowe, RN, at 919-966-7359 or donna_ rowe@med.unc.edu. The NLM Identifier is NCT01361113.

Pazopanib Versus Temsirolimus in PoorRisk Clear Cell RCC

This randomized, phase 2, open-label study compares pazopanib with temsirolimus in the treatment of patients with clear cell RCC. Pazopanib inhibits the growth of blood vessels that supply nutrients necessary for tumor growth, while temsirolimus blocks the growth of cancer cells. The study will assess the efficacy and safety of each drug, and is expected to enroll 90 patients. Participants will be allocated to receive 800 mg of pazopanib orally once daily or 25 mg of temsirolimus by infusion for 30 to 60 minutes weekly. Evaluations will occur at baseline, prior to treatment, and every 8 weeks.

Patients who are aged ≥18 years with pathologic evidence of metastatic or locally advanced RCC with a clear cell component and disease state measurable by Response Evaluation Criteria in Solid Tumors are eligible to participate in the study if other criteria are met. The primary outcome is progression-free survival (PFS), measured every 8 weeks from baseline to disease progression. PFS is defined as the time from initiation of the study drug to time of first disease progression. Radiologic studies using computed to-

44

october 2014 • Volume 5, number 5

mography or magnetic resonance imaging will be performed every 8 weeks to evaluate response. This study will be conducted at the University of Texas MD Anderson Cancer Center in Houston. For more information, contact Nizar M. Tannir, MD, Principal Investigator, at 713-7922830. The NLM Identifier is NCT01392183.

Safety, Pharmacokinetics, and Effectiveness of AGS-16C3F Monotherapy in RCC

In this phase 1, open-label, multicenter study, investigators are evaluating the safety, pharmacokinetics, and effectiveness of AGS-16C3F monotherapy in patients with RCC of clear cell or papillary histology. This study aims to establish a safe dose of AGS-16C3F by intravenous infusion and to assess safety and efficacy in 2 expanded cohorts.

The first cohort will include patients with clear cell histology, and the second cohort will include patients with papillary histology. The study expects to recruit 72 patients. To be eligible for study participation, patients should be aged ≥18 years, have a histologically confirmed diagnosis of metastatic RCC, have measurable disease according to Response Evaluation Criteria in Solid Tumors, and meet additional criteria.

The primary outcome measure of the study is incidence of adverse events within a 24-month time frame. Secondary outcomes include incidence of antibody formation and the measurement of tumor response. The study will be conducted in New York, Washington, and Michigan. For more information about the trial, contact Agensys Clinical Research and Development at 424-280-5000 or clinical@ agensys.com. The NLM Identifier is NCT01672775.

Cyberknife Radiosurgery in RCC

The purpose of this phase 2, open-label study is to evaluate the role of radiosurgery in patients with clinically localized primary RCC. This study is expected to enroll 46 patients. Participants will receive radiation doses based on the size of the tumor. Treatment will take 3 to 4 days, but no more than 14 days overall. To be eligible for this study, patients must be aged ≥18 years, have histologic evidence of stage I RCC with a tumor size of ≤8 cm, have at least 1 gold fiducial placed in or around the tumor, and meet additional inclusion and exclusion criteria.

The primary outcome of this study is to determine freedom from local tumor progression at 6 months in patients treated with CyberKnife radiosurgery. Secondary outcome measures include the impact of therapy on quality of life and an evaluation of adverse events. This study is being

AONNonline.org

A focus on the Commission on cancer

conducted at Beth Israel Deaconess Medical Center in Boston. For more information, contact Irving D. Kaplan, MD, at 617-667-2345 or ikaplan@caregroup.harvard.edu, or Nordine Benhaga, MD, at 617-667-4679 or nbenhaga@ bidmc.harvard.edu. The NLM Identifier is NCT01890590.

Hydroxychloroquine Before Surgery in Patients with Primary RCC

The purpose of this phase 1 study is to determine whether the use of hydroxychloroquine before nephrectomy in patients with primary RCC will facilitate the elimination of cancer cells; another goal is to examine the degree to which the study drug affects the patient’s immune system.

Biologic markers of autophagy in tumor and normal tissues, such as peripheral blood mononuclear cells and renal parenchyma, will be measured. Biologic markers will also be measured 1 month after surgery.

Patients who are aged ≥19 years with stage I to IV primary or metastatic RCC with a planned nephrectomy are eligible to participate in the study if additional criteria are met. This study is expected to enroll 20 patients and will be conducted at the University of Pittsburgh Medical Center, PA. For more information, contact Jodi K. Maranchie, MD, at 412-605-3019 or maranchiejk@upmc.edu, or Kimberly Jones, RN, BSN, at 412-623-2764. The NLM Identifier is NCT01144169.

Panobinostat and Everolimus in Patients with Metastatic or Unresectable RCC

The purpose of this phase 1/2, open-label, interventional study is to determine optimal dosing and potential side effects of panobinostat administered together with everolimus in patients with metastatic or unresectable RCC who did not respond to previous treatment with sunitinib malate or sorafenib tosylate. Patients in the first treatment arm will receive panobinostat orally once daily on days 1, 3, 4, 8, 10, and 12, and oral everolimus once daily on days 1 to 21. Treatment repeats every 21 days in the absence of disease progression or severe toxicity. This study is expected to enroll 48 patients.

To be eligible for participation, patients should be aged ≥18 years with a histologically confirmed diagnosis of metastatic or unresectable RCC, predominant clear cell component, and metastatic disease that has progressed within 6 months of stopping treatment; additional inclusion and exclusion criteria must be met. This study will be conducted in New York at the Roswell Park Cancer Institute in Buffalo and the University of Rochester Medical Center.

For more information, contact Roberto Pili, Principal Investigator, at 877-275-7724 or roberto.pili@roswellpark. org. The NLM Identifier is NCT01582009.

Dose Escalation of TRC105 in Combination with Axitinib in Patients with Advanced RCC

The goal of this phase 1, open-label study is to determine the optimal phase 2 dose for TRC105 when administered in combination with standard-dose axitinib in patients with advanced RCC. The study also assesses the safety and tolerability of TRC105 as part of this combination therapy.

The primary outcome measure of this study is to determine the maximum tolerated dose of TRC105 in combination with axitinib during a 1-year time frame. The secondary outcome is to assess plasma TRC105 concentration at specific time points.

It is estimated that 18 patients will be enrolled in this study. Patients who are aged ≥18 years with histologic evidence of advanced RCC whose disease has progressed following treatment with at least 1 previous therapy (sunitinib, pazopanib, sorafenib, tivozanib), and who have no history of other carcinomas within the past 5 years are eligible to participate in the study if additional criteria are met. Study locations include Alabama, California, and Massachusetts. For more information, contact Manoj Jivani at mjivani@traconpharma.com, or Bonne Adams at badams@traconpharma.com. The NLM Identifier is NCT01806064.

ASONEP in the Treatment of Refractory RCC

The objective of this phase 2, multicenter, open-label, single-arm study is to assess the efficacy, safety, and tolerability of ASONEP (sonepcizumab/LT1009) monotherapy in the treatment of patients with refractory RCC. It is estimated that the study will recruit 39 patients, and the treatment arm will consist of ASONEP 15 mg/kg administered by intravenous infusion over 90 minutes once a week every 4 consecutive weeks of patients’ treatment cycle. The primary outcome measure is progression-free survival evaluated at 8 weeks. The study will utilize a 2-cohort design; enrollment of cohort 2 will proceed depending on the rate of progression-free survival in cohort 1. Secondary outcome measures include safety and tolerability, measured as the incidence and frequency of adverse events.

To be eligible for the study, patients must be aged ≥18 years with unresectable and locally advanced recurrent or metastatic RCC, have histological evidence of clear cell RCC, demonstrate disease measurable by Response Evaluation Criteria in Solid Tumors, and meet other inclusion and exclusion criteria. Study locations include California, South Carolina, and Tennessee. For more information, contact France LaPierre-Holme, Study Director, at 858678-0800. The NLM Identifier is NCT01762033. g

JONS-online.com journal of Oncology Navigation & Survivorship

45

Patient Assistance Programs

Imbruvica YOU&i Access Program and Support for Patients

T

his article is the first in a series of 5 articles to run in The Journal of Oncology Navigation & Survivorship on patient assistance programs. The information belowâ&#x20AC;&#x201D;highlighting an assistance program for patients who are prescribed Imbruvicaâ&#x20AC;&#x201D;was provided by Pharmacyclics, Inc, and Janssen Biotech, Inc

YOU&i Access Programs

When Pharmacyclics and Janssen Biotech set out to launch Imbruvica in the United States, they prioritized one goal above all others: providing access support to patients who are prescribed Imbruvica. Improving access for patients is challenging due to the complicated nature of the reimbursement landscape. What might help improve access for a patient with commercial insurance may not be available or allowed for a patient with government-funded insurance. Patients may have higher out-of-pocket costs in certain months versus others. To help make access to Imbruvica simple, convenient, and easy for a variety of patients, Pharmacyclics and Janssen Biotech created a unique set of patient support programs called YOU&i Access programs.

For commercial patients, Pharmacyclics and Janssen Biotech offer the YOU&i Access Instant Savings Program to help with out-of-pocket expenses for Imbruvica. This program enables eligible patients with commercial insurance to pay a copay of $25 per month,a regardless of income level. The patient can use as much or as little as they need in each month.

For patients experiencing insurance coverage decision delays, Pharmacyclics and Janssen Biotech offer the YOU&i Start Program. This program offers eligible patients who have been prescribed Imbruvica for a US Food and Drug Administration-approved indication, and who are experiencing an insurance coverage decision delay of

46

october 2014 â&#x20AC;˘ Volume 5, number 5

greater than 5 business days, a free 30-day supply of Imbruvica. Under appropriate circumstances, an additional 30day supply may be provided. The free product is offered to eligible patients without any purchase contingencies or other obligations.

Improving access for patients is challenging due to the complicated nature of the reimbursement landscape.

What might help improve access for a patient with commercial insurance may not be available or allowed for a patient with government-funded insurance.

For uninsured patients, the Johnson & Johnson Patient Assistance Foundation, an independent, nonprofit organization, may offer assistance with accessing Imbruvica to eligible patients who qualify based on financial need (income requirement of 600% of the federal poverty level).

Lastly, for all patients with chronic lymphocytic leukemia (CLL) and mantle-cell lymphoma (MCL), Pharmacyclics and Janssen Biotech support third-party copay assistance foundations, organizations, and other efforts to help any patients gain access to appropriate care and therapies.

Pharmacyclics and Janssen Biotech have supported and continue to support third-party foundations to assist patients living with CLL or MCL. For more information, visit www.youandiaccess.com or call 877-877-3536. g Month refers to a 30-day supply subject to a maximum benefit, 12 months after activation or 12 monthly fills (1-year supply), whichever comes first, unless the maximum dollar benefit has been reached. Not valid for patients enrolled in Medicare or Medicaid.

a

AONNonline.org

unc

le

FACES

r siste

her t o m

HopE

â&#x201E;˘

of

The Academy of Oncology Nurse & Patient Navigators (AONN+) invites you to share your story of how cancer has affected you or a loved one. These stories will serve as a forum to build awareness and be a source of inspiration and reassurance to others. Select stories will be featured on the AONN+ website and in future issues of the Journal of Oncology Navigation & Survivorship ÂŽ.

ndm oth er

nephew

5

5

YEAR A N N I V E RS A RY

YEAR A N N IV E R S A RY

nd

ie t fr

bes

AONNFacesofHopeAsize_53014

er broth

Share Your StorY With uS!

AONNonline.org/community/aonn-faces-of-hope

A legacy of innovation, partnership, and patient care

Lilly Oncology is committed to making a meaningful difference for patients by answering the complex questions of cancer care. Weâ&#x20AC;&#x2122;re partnering with organizations all over the world to provide valued resources and support.

To learn more, visit www.LillyOncology.com.

CA20531 08/2013

PRINTED IN USA

Š2013, Lilly USA, LLC. ALL RIGHTS RESERVED.