TOP February 2015

FEBRUARY 2015

www.TheOncologyPharmacist.com

VOL 8, NO 1

BEST PRACTICES

CANCER CENTER PROFILE

St. Joseph’s/Candler Health System

Biosimilars: Ambiguity of FDA Terminology and Benefits of a Multidisciplinary Review Team Chase Doyle

B Colleagues at St. Joseph’s/Candler Health System (left to right): Nikki Moody, RPhT; Trish Amelung, RN, OCN; Sheila Charron, RN, OCN; Nancy M. Nix, PharmD, BCPS, BCOP; Ann Podnar-Calvo, RN, OCN; and Margie Martin, RN, CRNI.

S

t. Joseph’s/Candler Health System was established through a joint operating agreement between 2 religious institutions—St. Joseph’s, a Catholic hospital, and Candler, a Methodist hospital. It is the only faith-based healthcare system in southeast Georgia. St. Joseph’s/Candler takes a holistic approach to healing, with a mission statement that reads, “We treat illness and promote wellness for all people.”

The Nancy N. and J.C. Lewis Cancer & Research Pavilion, located in Savannah, GA, is part of St. Joseph’s/Candler and comprises radiation oncology, medical oncology, and infusion services. It is a national Community Oncology Research Program, as selected by the National Cancer Institute, Continued on page 22

SYMPTOM MANAGEMENT

Symptom Management Drives Value in Oncology Chase Doyle

S

an Diego, CA—The development of standardized methods of patient assessment through a symptom management clinic (SMC) leads to better quality care, improved patient satisfaction, and a significant reduction in costs, according to a study presented at the 2014 Association of Community Cancer Centers’ National Oncology Conference.

For Lynn Graze, RN, MSN, OCN, Nursing Director at the DeCesaris Cancer Institute of the Anne Arundel

Medical Center in Annapolis, MD, the idea for the symptom management clinic emerged from a drive to achieve higher-quality care at lower cost.

Establishing the Symptom Management Clinic In 2011 “we started to see that systematic nursing assessments with interventions lead to better quality of life for patients. We also saw that unrelieved symptoms lead to a decline in physical state, performance status, and increased

ecause of the complexity of biosimilar regulations, a pharmaceutical and therapeutics (P&T) committee—which includes pharmacists and physicians—is recommended to determine appropriate biosimilar use, according to a presentation at the Oncology Pharmacy Education Network Pre-Conference of the Association of Community Cancer Centers’ 2014 National Oncology Conference, held recently in San Diego, CA. Jim Koeller, MS, professor at the University of Texas at Austin College of Pharmacy and the Health Science

Center in San Antonio, discussed the need to place the P&T committee front and center. In extolling its virtues, Koeller quipped, “A P&T committee is almost like god. They can say, ‘let there be light,’ and there is light.”

Promoting a case-by-case approach to the approval of a biosimilar, the US Food and Drug Administration (FDA) requires a biosimilar application to show that there are no clinically meaningful differences in safety, purity, and potency between the biosimilar and the US-licensed reference product.

Analytical data, animal testing data, and Continued on page 10

BEST PRACTICES

Addressing Patient Safety for Oral Chemotherapy Alice Goodman

T

he expanding availability of oral drugs for the treatment of a number of tumor types has increased their use as chemotherapy. Patients prefer the convenience of oral drugs as long as they are as effective as intravenous (IV) drugs, but the increasing use of oral chemotherapy has brought new challenges to the oncology community

in terms of prescribing, dispensing, safe handling, and monitoring.

How best to address these challenges was explored by Monika Krzyzanowska, MD, MPH, FRCPC, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, at the recent American Society of Clinical Oncology (ASCO) Quality Care Symposium.1 Continued on page 18

I N S I D E CONFERENCE NEWS. . . . . . . . . . . .

Highlights from ASH and SABCS

5 8

HODGKIN LYMPHOMA . . . . . . . . . .

Immunotherapy the Newest Breakthrough in Hodgkin Lymphoma

Continued on page 14 © 2015 Green Hill Healthcare Communications, LLC

FDA UPDATE. . . . . . . . . . . . . . . . . . . . 10 Jakafi Gets New Indication for Use in Patients with Polycythemia Vera IMMUNOTHERAPY . . . . . . . . . . . . .

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EDITORIAL BOARD EDITOR-IN-CHIEF

Patrick Medina, PharmD, BCOP Oklahoma University College of Pharmacy Tulsa, OK

Anjana Elefante, PharmD, BSc, BSc Pharm, RPh

Dwight Kloth, PharmD, FCCP, BCOP

Timothy G. Tyler, PharmD, FCSHP

Beth Faiman, PhD, MSN, APRN-BC, AOCN

Jim Koeller, MS

John M. Valgus, PharmD, BCOP

Christopher Fausel, PharmD

Christopher J. Lowe, PharmD

Roswell Park Cancer Institute Buffalo, NY

Fox Chase Cancer Center Philadelphia, PA

Desert Regional Medical Center Palm Springs, CA

ASSOCIATE EDITOR-IN-CHIEF

Steve Stricker, PharmD, MS, BCOP Samford University McWhorter School of Pharmacy Birmingham, AL

John F. Aforismo, BSc Pharm, RPh, FASCP

University of Texas at Austin San Antonio, TX

Cleveland Clinic Taussig Cancer Institute Cleveland, OH

Drug Knowledge Wethersfield, CT

Indiana University Simon Cancer Center Indianapolis, IN

Indiana University Hospital Indianapolis, IN

David Baribeault, BS, BCOP

Rebecca S. Finley, PharmD, MS

Emily Mackler, PharmD, BCOP

Betty M. Chan, PharmD, BCOP

David C. Gammon, BSPh

Laura Boehnke Michaud, PharmD, BCOP, FASHP

Boston, MA

USC/Norris Cancer Hospital Los Angeles, CA

Jefferson School of Pharmacy Philadelphia, PA

OncologyPharmacist.net Warwick, RI

University of Michigan Health System & College of Pharmacy Ann Arbor, MI

The University of Texas MD Anderson Cancer Center Houston, TX

University of North Carolina Hospitals and Clinics Chapel Hill, NC

Gary C. Yee, PharmD, FCCP, BCOP University of Nebraska College of Pharmacy Omaha, NE

Burt Zweigenhaft, BS

Onco360/OncoMed New York, NY

Marlo Blazer, PharmD, BCOP James Cancer Hospital & Solove Research Institute Columbus, OH

Heidi D. Gunderson, PharmD, BCOP Mayo Clinic Cancer Center Rochester, MN

Steven L. D’Amato, RPh, BCOP Maine Center for Cancer Medicine Scarborough, ME

www.TheOncologyPharmacist.com

Lew Iacovelli, BS, PharmD, BCOP, CPP

Moses H. Cone Health System Greensboro, NC

LeAnn Best Norris, PharmD, BCPS, BCOP South Carolina College of Pharmacy Columbia, SC

Kamakshi V. Rao, PharmD, BCOP University of North Carolina Hospitals and Clinics Chapel Hill, NC

FEBRUARY 2015 I VOL 8, NO 1

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FROM THE EDITORS

PUBLISHING STAFF Senior Vice President, Sales & Marketing Nicholas Englezos nenglezos@the-lynx-group.com Vice President/Group Publisher Russell Hennessy rhennessy@the-lynx-group.com Vice President/Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Publisher Cristopher Pires cpires@the-lynx-group.com Editorial Directors Kristin Siyahian ksiyahian@the-lynx-group.com Frederique H. Evans fevans@the-lynx-group.com Copyeditors Hina Khaliq Mollie Friedman Peggy Roeske Production Manager Cara Nicolini

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Green Hill Healthcare Communications, LLC 1249 South River Road - Ste 202A Cranbury, NJ 08512 phone: 732-656-7935 • fax: 732-656-7938

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FEBRUARY 2015 I VOL 8, NO 1

Editor-in-Chief Patrick Medina, PharmD, BCOP

In its eighth year, The Oncology Pharmacist (TOP) will continue to provide oncology pharmacists and their colleagues with the latest research findings and results of large clinical trials, interviews with thought leaders, as well as content for pharmacy students and residents, and articles on practice management.

In particular, this issue of TOP features a cancer center profile from St. Joseph’s/Candler Health System, best practices in care in cancer care—including an article on biosimilars and patient safety for oral chemotherapy—and a column on the economics of cancer care. We also provide conference highlights from the American Society of Hematology, the San Antonio Breast Cancer Symposium, and the World Cutaneous

Associate Editor-in-Chief Steve Stricker, PharmD, MS, BCOP

Malignancies Congress.

This February issue also features the first column on wealth management, with a column by Andrew D. Schwartz, CPA, and Lawrence B. Keller, CFP, CFU, CLU, ChFC, RHU, LUTCF, providing 8 ways to improve your finances.

The issue is also available on the TOP website, at TheOncologyPharmacist.com. Take some time to go through it and send us feedback on articles you enjoyed, and be sure to vote on the current poll. Comments can also be sent to editorial@greenhillhc.com.

We thank the editorial board of TOP and contributors for their continued efforts in 2015, and wish the readers of the journal all the best for the new year. l

READER POLL Do you encourage self-reporting in patients receiving oral chemotherapy? o Yes o No In an article on patient safety and oral chemotherapy (the cover), Monika Krzyzanowska, MD, MPH, FRCPC, discusses the need to identify effective tools, assess effectiveness, and promote incident reporting.

Do you encourage self-reporting in patients receiving oral chemotherapy? Tell us about your methods for addressing patient safety in oral chemotherapy, and provide your feedback on this article.

Go to www.TheOncologyPharmacist.com to answer the question and add your comments.

The Oncology Pharmacist®, ISSN 1944-9607 (print); ISSN 1944-9593 (online) is published 4 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 © 2015 by Green Hill Healthcare Communications, LLC. All rights reserved. The Oncology Pharmacist® 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 DIRECTOR, The Oncology Pharmacist®, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. E-mail: editorial@greenhillhc.com. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issues, $17.00. 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 The Oncology Pharmacist® do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mentioned in The Oncology Pharmacist® 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.

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CONFERENCE NEWS

Highlights from ASH and SABCS Alice Goodman

T

he annual meetings of the American Society of Hematology (ASH) and the San Antonio Breast Cancer Symposium (SABCS) took place in December 2014, attracting US and international oncologists interested in the latest research on basic science and clinical medicine. Below is a selection of highlights from these meetings.

ASH Announces Second Choosing Wisely List leukemia • Do not test or treat for suspected heparin-induced thrombocytopenia (HIT) in patients with a low pretest probability of HIT

© American Society of Hematology. All rights reserved.

ASH an­ nounced its second list of 5 commonly used tests, treatments, and procedures in hematology that physicians and patients should discuss before routine use. This Choosing Wisely list adds to the first list of 5 practices that the society released in 2013 as part of the Choosing Wisely campaign, an initiative of the American Board of Internal Medicine (ABIM) Foundation that intends to spark conversations between patients and physicians about the risks and benefits of certain procedures.1 ASH’s new Choosing Wisely recommen dations include the following2: • Do not treat with an anticoagulant for >3 months in a patient with a first venous thromboembolism occurring in the setting of a major transient risk factor • Do not routinely transfuse patients with sickle-cell disease for chronic anemia or uncomplicated pain crisis without an appropriate clinical indication • Do not perform baseline or routine surveillance computed tomography scans in patients with asymptomatic, early-stage chronic lymphocytic

• Do not treat patients with immune thrombocytopenic purpura in the absence of bleeding or a very low platelet count.

“Unnecessary treatments or tests not only add waste to the healthcare system, but in some cases, they also expose our patients to a risk of

harm,” said Lisa Hicks, MD, of St. Michael’s Hospital and the University of Toronto, Ontario, Canada, and chair of the ASH Choosing Wisely Task Force. “ASH developed its second

“Unnecessary treatments or tests not only add waste to the healthcare system, but in some cases, they also expose our patients to a risk of harm.”

Lisa Hicks, MD

Choosing Wisely list to help hematologists manage the utilization and delivery of patient care resources, and ASH encourages hematologists to consider these recommendations in all facets of their work including patient care, teaching, innovation, and research.”

The guiding principle for the prac-

tices included in Choosing Wisely is to do no harm. Other principles guiding ASH’s choices for the lists include strength of evidence, aggregate cost, frequency, making recommendations within the purview of hematology, and potential impact in the field.3 Since the launch of the Choosing Wisely campaign in April 2012, more than 100 national and state medical specialty societies, regional health collaborative organizations, and consumer partners have joined this initiative aimed at providing appropriate care to patients.4 Consumer Reports has joined the effort, spreading the word to patients all over the country to stimulate discussions between physicians and patients about these and other practices. l References

1. Choosing wisely: an initiative of the ABIM Foundation. www.ChoosingWisely.org. Accessed January 15, 2015.

2. American Society of Hematology. The ASH Choosing Wisely List. www.hematology.org/Clinicians/Guide lines-Quality/502.aspx. Accessed January 15, 2015.

3. Choosing wisely: an initiative of the ABIM Foundation. Lists. www.choosingwisely.org/doctor-­ patient-lists/. Accessed January 15, 2015.

4. Choosing wisely: an initiative of the ABIM Foundation. Partners. www.choosingwisely.org/partners.

Accessed January 15, 2015.

Dietary Fat Intake Studied in Patients with Early-Stage Breast Cancer ry analysis found a 36% reduction in mortality rates of women with estrogen receptor–negative breast cancer who lowered their dietary fat intake.

Photo Courtesy © SABCS/Todd Buchanan 2012

Women who limited their intake of dietary fat for 5 years after being diagnosed with early-stage breast cancer significantly reduced the mortality rate from all causes at 15 years of follow-up; this occurred specifically in women with hormone-unrelated cancer. No long-term effect of dietary fat reduction on mortality was observed in women with hormone receptor–positive breast cancer. The study was presented at the 2014 SABCS. “These findings with respect to longterm influence of dietary lifestyle intervention on overall survival are mixed, but of potential importance,” said lead author Rowan T. Chlebow­ski, MD, PhD, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.

At 15 years, the overall mortality rate was lower in the dietary intervention group in the overall analysis compared with those in the control group, but the difference between the groups did not reach statistical significance (13.6% vs 17%, respectively). An explorato-

The Women’s Intervention Nutrition Study enrolled 2437 women with early-stage breast cancer who were treated with standard care at 39 centers in the United States. Ages at

enrollment were between 48 and 79 years.

Of this group, 1597 had estrogen receptor–positive breast cancer, 478

“These findings with respect to long-term influence of dietary lifestyle intervention on overall survival are mixed, but of potential importance.”

Rowan T. Chlebowski, MD, PhD

had estrogen receptor–negative breast cancer, and 362 had estrogen receptor–negative/progesterone receptor– negative breast cancer. Within the first 6 months following diagnosis,

women were randomized to a dietary fat intervention (N = 975) or control group (N = 1642).

In the intervention group, centrally trained dietitians counseled women for 8 biweekly individual sessions on how to implement a low-fat diet. Women were then contacted by dietitians every 3 months for 5 years. Women assigned to the dietary intervention group kept written records of their fat/gram intake.

At 5 years, calorie intake was 8.9% lower in the intervention group, and these women lost about 6 pounds when compared with the control group.

Dr Chlebowski noted that human epidermal growth factor receptor 2 status was not assessed at the time this study was being conducted, but suggested that women with triple-negative breast cancer (estrogen receptor–negative/progesterone receptor–negative/ and HER2-negative status) may also benefit from dietary fat reduction. In general, lowering dietary fat is a good idea for general health, he added. l Continued on page 6

www.TheOncologyPharmacist.com

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CONFERENCE NEWS Continued from page 5

Pediatric Regimens the New Standard for Adolescents and Young Adults with ALL North America to evaluate treatment with a pediatric intensive regimen delivered by adult hematologists/oncologists.

Dr Stock presented the main results of the trial. Additional analysis of adherence and outcomes based on psychoso-

© American Society of Hematology. All rights reserved.

Early results of the large, prospective intergroup trial, C10403, demon­ strate that a pediatric-inspired regimen improves event­-free survival (EFS) and overall survival (OS) in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL). Many smaller studies have shown that AYAs have improved outcomes on pediatric regimens, but this is the first large data set to validate this practice. Two-year EFS was 66%, and 2-year OS was 78%.

“These results are a major improvement compared with 34% and 39%, respectively, in historical controls.

This is a clear opportunity to improve care in AYAs with ALL,” said lead author Wendy Stock, MD, University of Chicago Medical Center in Illinois.

The study showed that the presence of a BCR-ABL1–like signature and aberrant CRLF2 expression were associated with worse EFS and OS; patients without these features had excellent EFS and OS, Dr Stock told listeners at the 2014 annual meeting of ASH. The intergroup C10403 trial was undertaken by cooperative groups in

cial factors will be presented in the future.

From 2007 to 2012, 296 AYA patients with ALL were treated. Median age was 24 years; 75% were white, 10% were African American, and 15% were

Hispanic/Latino. Seventy-six percent had B-precursor ALL, and 24% had T-precursor ALL. Thirty-two percent of patients had a body mass index of ≥30, and 7% were morbidly obese.

The backbone of the pediatric­

“These results are a major improvement compared with 34% and 39%, respectively, in historical controls. This is a clear opportunity to improve care in AYAs with ALL.” Wendy Stock, MD

inspired regimen included intensified glucocorticoid, vincristine, and asparaginase, and more maintenance therapy. The regimen included remission induction and consolidation, interim

maintenance, delayed intensification, and prolonged maintenance—2 years in women, and 3 years in men.

EFS was similar regardless of agegroup or precursor B- or T-lineage.

OS was significantly worse in obese patients, and significantly improved in patients with undetectable minimal residual disease (MRD).

Dr Stock and colleagues are planning to propose a successive US intergroup trial that should begin in 2015. The plans include use of the molecular signature of the disease to stratify patients and the addition of either a novel antibody or tyrosine kinase inhibitor to eradicate MRD and improve outcomes.

“This is a phenomenal achievement,” said Yoav Messinger, MD, a pediatric oncologist at Children’s Hospitals and Clinics of Minnesota in Minneapolis, and chairman of the session where these data were presented. “We have been waiting for a long time for these data, which put what we already know into a formalized protocol on a large-scale basis.” l

Tinzaparin Is Safe and Effective in Reducing Risk for Recurrent Venous Thromboembolism recurrent blood clots,” said Dr Lee. Patients with cancer are at increased risk for VTE and DVT, which present major challenges for treatment, © American Society of Hematology. All rights reserved.

Tinzaparin, a low­-molecular­-weight heparin (LMWH), reduced the risk of recurrent venous thromboembolism (VTE) in patients with active cancer, lowered the risk of symptomatic deep vein thrombosis (DVT), and did not increase the risk of major bleeding despite full-dose use in the randomized, open-label CATCH study reported at the 2014 annual meeting of ASH by Agnes Lee, MD, University of British Columbia, Vancouver, Canada.

“Thrombosis is a common, deadly, and costly complication of cancer. Some tumors place patients at higher risk, including pancreatic, lung, co­lorectal, gastrointestinal, and brain cancer. As the largest randomized, controlled trial on the treatment of thrombosis among cancer patients, this study reinforces clinical guidelines supporting the use of LMWH instead of warfarin to prevent

balancing the risks of bleeding with the benefits of blood clot dissolution.

Current guidelines recommend the use of LMWH to reduce the risk of clotting—however, this recommendation was based on a single trial. Given the

lack of confirmatory trials or trials of different medications, warfarin is commonly used as an anticoagulant in cancer patients.

“Thrombosis is a common, deadly, and costly complication of cancer.”

Agnes Lee, MD

CATCH enrolled 900 cancer pa­ tients with DVT or pulmonary embolism at 165 different centers around the world to evaluate the efficacy and safety of tinzaparin versus warfarin. Patients were randomized to receive tinzaparin

once daily for 6 months, or tinzaparin once daily for 5 to 10 days followed by 6 months of warfarin.

During treatment, 31 patients (6.9%) experienced recurrent VTE on tinzaparin versus 45 (10%) of the patients treated with warfarin, representing a 35% reduction in the risk of recurrent VTE. However, this difference was not statistically significant.

Tinzaparin reduced the risk of symptomatic DVT by 52% compared with the warfarin arm, and this difference was statistically significant (P = .04).

Tinzaparin also reduced clinically relevant nonmajor bleeding (11% vs 16%, respectively; P = .03).

“This study validates the superiority of LMWH,” Dr Lee said. “Although LMWH is much more expensive than warfarin, there is no need for continual monitoring as there is with warfarin.” l

Single-Agent Capecitabine Fails to Improve Outcomes in Elderly Patients with Breast Cancer Adjuvant therapy with cape­ citabine plus ibandronate does not improve outcomes compared with ibandronate alone in elderly patients with moderateto­-high-risk early­-stage breast cancer in

the ICE (Ibandronate With or Without Capecitabine in Elderly Patients With Early Breast Cancer) study. Toxic effects of anthracyclines and taxanes would improve outcomes. The women

included in this trial were not candidates for conventional chemotherapy with taxanes and anthracyclines. The hope was that an oral therapy free of the side effects of combination chemother-

apy could improve outcomes.

Lead author of ICE, Gunter von Minckwitz, MD, University of Frankfurt, Germany, and chairman of the German Breast Group, said that capecitabine is Continued on page 7

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FEBRUARY 2015 I VOL 8, NO 1

www.TheOncologyPharmacist.com

LEUKEMIA

Venetoclax Moves Forward in Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia Phoebe Starr

San Francisco, CA—The results of a phase 1b study of the combination of venetoclax plus rituximab (Rituxan) showed encouraging safety and excellent activity in patients with chronic lymphocytic leukemia (CLL). Venetoclax will move on to a phase 3 trial comparing venetoclax plus ri­tuximab versus bendamustine (Treanda) plus rituximab in patients with previously treated CLL. The drug is also being studied in acute myeloid leukemia (AML).

The study included 49 patients with relapsed/refractory CLL who had a maximum of 3 previous myelosuppressive regimens and no previous transplant.

The complete response (CR) rate was encouraging.

“Venetoclax plus rituximab is highly active in relapsed/refractory CLL, achieving an overall response rate of 88% and a complete response rate of 31%. The results suggest that rituximab adds to the efficacy of venetoclax,” said lead investigator Andrew W. Roberts, MBBS, PhD, Bone Marrow Transplant Physician and Clinical Hematologist, Royal Melbourne Hospital, Parkville, Victoria, Australia.

“Seventeen patients became minimal residual disease-negative on treatment, which is impressive bone marrow clearance,” Dr Roberts noted.

Venetoclax (formerly ABT-199/ GDC-­0199) is an oral selective BCL-2 inhibitor that rapidly induces responses in approximately 80% of patients with

“Venetoclax plus rituximab is highly active in relapsed/refractory CLL, achieving an overall response rate of 88% and a complete response rate of 31%.”

Andrew W. Roberts, MBBS, PhD

relapsed/refractory CLL as a single agent.

Venetoclax has synergy with rituximab in preclinical models of CD20-positive lymphoid malignancies. This study was undertaken to determine if the addition of rituximab would improve the efficacy of venetoclax.

The study was designed to identify a maximal tolerated dose of venetoclax and the optimal schedule for using the drug with rituximab and the safety of the combination, but remarkable bone marrow clearance was observed with this combination, said Dr Roberts.

Discontinuations were reported in 10 patients, 1 after the occurrence of tumor lysis syndrome, which led to adjustments in the schedule by modifying the dose of venetoclax and giving 1 dose of rituximab every 4 weeks. “The new schedule overcomes tumor lysis syndrome,” Dr Roberts said.

Venetoclax was generally well-toler-

ated, with mild gastrointestinal toxic­ ity and grade 3 or 4 myelosuppression (47% neutropenia, 16% thrombocytopenia, and 14% anemia).

The overall response rate was 88%; 31% of patients achieved CR or CR with incomplete platelet recovery, 45% showed partial response (PR), and 12% showed unconfirmed PR. “Good responses to the combination were observed in patients with del17p, known to have poor prognosis,” Dr Roberts said.

Overall, 9 of the 15 patients who achieved CR showed no minimal residual disease, and 1 patient with CR

“AML is an aggressive cancer with low survival rates, and there is a high need for new, effective treatment options.

The results of this trial of venetoclax are encouraging.”

Marina Y. Konopleva, MD, PhD

showed no minimal residual disease at 14 months. Of the patients with PR, 8 had no minimal residual disease. Of the 5 patients who achieved CR and discontinued therapy, none has progressed

to date (up to 26 weeks).

Based on toxicity and efficacy data, 400 mg is the recommended dose.

Slightly more neutropenia, gastrointestinal toxicity, and dose reductions were observed at higher doses.

During the question and answer session, Dr Roberts was asked about biomarkers for venetoclax. He said that most patients with CLL express BCL2 and are sensitive to this drug, and, in his opinion, biomarkers for response are not needed in this setting.

Acute Myeloid Leukemia A separate presentation showed en­­ couraging first results from a phase 2 clinical trial evaluating venetoclax in patients with AML, justifying further investigation of this drug in AML. Venetoclax achieved an overall response rate of 15.5%; there were 5 patients who achieved CR, 4 of whom had incomplete platelet recovery. These responses were in patients with relapsed/ refractory AML or patients who received venetoclax as frontline therapy but who were unfit for intensive treatment.

“AML is an aggressive cancer with low survival rates, and there is a high need for new, effective treatment options. The results of this trial of venetoclax are encouraging and warrant additional study in patients with AML,” said Marina Y. Konopleva, MD, PhD, Associate Professor, Department of Leukemia, M.D. Anderson Cancer Center, Houston. l

CONFERENCE NEWS Continued from page 6

frequently used in elderly patients who cannot tolerate the side effects of conventional chemotherapy—but these findings no longer support that practice.

Three-year invasive disease-free survival (DFS) was 85.4% for those who received the capecitabine/ibandronate treatment arm versus 84.3% in the ibandronate arm; 5-year invasive DFS was 78.8% versus 75%, respectively.

ICE was a prospective, randomized, multicenter trial that enrolled 1380 patients with node-positive or highrisk node-negative early breast cancer.

Women aged ≥65 years were randomized in a 1:1 ratio to capecitabine plus ibandronate or ibandronate alone for 2 years of treatment. At the time the study was initiated, ibandronate was thought to have a protective effect against breast cancer.

Mean age was 71 years, and about 25%

www.TheOncologyPharmacist.com

Photo Courtesy © SABCS/Todd Buchanan 2012

Single-Agent Capecitabine Fails to Improve Outcomes in Elderly...

were aged 75 years or older. About 10% had a Charlson Comorbidity Index score of 2. One third of patients were receiving ≥3 medications for comorbidities. About 14% had triple-negative breast cancer, about 80% had hormone receptor–posi-

—occurred in 25% of the patients in the capecitabine/ibandronate group “These results, versus 24.7% receiving ibandronate together with results alone. It did not make a difference whether ibandronate was given intraof CALGB 49907, venously (about 35%) or orally (about strongly support the 65%). Results of treatment were similar across all subgroups. use of combination “These results, together with results chemotherapy in of CALGB 49907, strongly support the use of combination chemotherapy elderly patients.” in elderly patients,” Dr von Minckwitz Gunter von Minckwitz, MD said. CALGB 49907 compared capeci­ tabine versus combination chemotherapy in elderly women and found that tive breast cancer, and about 70% were combination chemotherapy was supeon aromatase inhibitors only. rior and could be given to patients Interestingly, ibandronate did not with a reasonable life expectancy. prevent bone-related events in this “A patient has to be really unfit [for study. Fractures, surgery, and new os­ me to] not give her chemotherapy,” teoporosis—excluding bone metastases­ he added. l

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HODGKIN LYMPHOMA

Immunotherapy the Newest Breakthrough in Hodgkin Lymphoma Impressive response rates with new PD-1 inhibitors

Nivolumab Nivolumab was tested in 23 patients with Hodgkin lymphoma, 87% of whom had received previous treatment with at least 3 regimens, including stem-cell transplant and brentuximab vedotin (Adcetris). In all, 35% of the patients had received at least 6 previous regimens. All tumors had genetic abnormalities involving 9p24.1, leading to overexpression of the PD-1 ligands.

Nivolumab 3 mg/kg was administered every 2 weeks until disease progression or severe toxicity.

“Treatment resulted in a response rate of 87%, which is quite high for patients who were heavily pretreated,” said lead investigator Philippe Armand, MD, PhD, Senior Physician,

“Treatment [with nivolumab] resulted in a response rate of 87%, which is quite high for patients who were heavily pretreated.”

Philippe Armand, MD, PhD

Hematologic Malignancies, Dana-­ Farber Cancer Institute, Boston.

Responses were seen in the 100% of patients who had not undergone a stemcell transplant and in 80% who had a transplant but did not receive brentuximab. At an average of 40 weeks, the complete response rate was 17% overall, and 60% in brentuximab-naïve patients. Another 13% of patients had stable disease.

The progression-free survival rate was 86% at 24 weeks. At the time of data assessment, 48% of the responses were ongoing, and 43% of patients were still receiving treatment. Some patients have been in remission for >1 year, said Dr Armand.

The safety profile of nivolumab mirrored that in solid tumors. Overall, 22% of patients had grade 3 drug-related adverse events (AEs); no deaths or drug-related grade 4 AEs were reported.

Two patients discontinued treatment as a result of AEs. “There was no apparent increase in lung toxicity, which we worry about, because many patients had other treatments that can cause lung injury,” Dr Armand said.

In May of this year, the FDA granted nivo­lumab a breakthrough therapy designation for relapsed Hodgkin lymphoma.

Pembrolizumab Pembrolizumab was evaluated in 29 heavily pretreated patients with

© American Society of Hematology. All rights reserved.

San Francisco, CA—Two programmed cell death receptor-1 (PD-1) inhibitors—the investigational drug nivo­ lumab and the recently approved pem­bro­lizumab (Keytruda)—produced dramatic responses in patients with Hodg­kin lymphoma in phase 1 clinical trials. Complete or partial responses were reported by up to 87% of patients who had exhausted other treatment options, providing solid evidence that targeting the immune system can be effective in hematologic malignancies, similar to solid tumors. The data were presented at the 2014 American Society of Hematology meeting.

“Strategies that target tumor cells using the immune system are extremely exciting,” said Catherine M. Bollard, MBChB, MD, Blood and Marrow Transplant Specialist, Children’s National Health System, and Professor of Microbiology, Immunology, and Tropical Medicine, George Washington University, Washington, DC. “I see this as a way forward in how we will revolutionize treatments in hematology.”

© American Society of Hematology. All rights reserved.

Wayne Kuznar

“Almost all patients had some evidence of tumor shrinkage….

Many patients had stable disease on pembrolizumab.”

Craig H. Moskowitz, MD

classic Hodgkin lymphoma who had progressed after treatment with brentuximab vedotin. Craig H. Mosko­ witz, MD, Clinical Director, Division

of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, New York, presented the results of the trial at the meeting.

The response rate was 66%, reported Dr Moskowitz, with complete responses in 21% of the patients and partial responses in 45%. Responses occurred in 75% of the patients with previous stem-cell transplant and in 44% of those who were transplant-ineligible or who had refused transplant.

The median time to response was 12 weeks, and the median duration of response was not reached. “Almost all patients had some evidence of tumor shrinkage,” Dr Moskowitz said.

The clinical benefit rate, which includes stable disease, was 86%.

“Many patients had stable disease on pembrolizumab. In fact, some who have been on treatment the longest had stable disease,” he said.

Pembrolizumab 10 mg/kg was administered every 2 weeks until progressive disease, excessive toxicity, or the completion of 24 months of therapy. Overall, 52% of the patients had received at least 5 previous lines of treatment. All patients had previously failed therapy with brentuximab, and 69% had stem-cell transplant failure.

There were 4 treatment-related grade ≥3 AEs—1 patient each with axillary pain, hypoxia, joint swelling, and pneumonitis. There were no grade 4 AEs or treatment-related deaths.

Pembrolizumab and nivolumab have individually demonstrated single-­ agent activity in patients with Hodgkin lymphoma, said Dr Moskowitz, commenting on these results. He noted that future evaluations in combination with standard therapies, or even as maintenance treatment to enhance the posttransplant immune response will be important. l

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BEST PRACTICES

Biosimilars: Ambiguity of FDA Terminology and Benefits... Continued from cover clinical study data (including immunogenicity and pharmacokinetics/pharmacodynamics evaluation) must show that a product is “highly similar” or “biosimilar” to the approved biologic and at least approximates the original safety and efficacy.

Many Unanswered Questions Koeller underscored the ambiguity of the FDA’s regulations: “How similar is similar enough to be defined as highly similar when it comes to a complex biologic?” he asked the audience rhetorically. “What structural difference will be compatible with the concept of highly similar? These questions are still open to interpretation.”

Although the FDA has released 3 draft guidances, many unanswered questions remain, especially with regard to interchangeability. The FDA views the biosimilar designation and interchangeable designation as 2 distinct steps.

“The product will first have to be deemed biosimilar,” explained Koeller.

“Then the company will have to come back with additional data to obtain the interchangeable indication. This would indicate that a product will have to be on the market first as a biosimilar prior

to its approval as interchangeable.” To be found interchangeable, a product must be expected to produce the same clinical results as the reference product.

tainties regarding the “approval step approach” and all of the required data (including clinical review), Koeller suggested initial cost-savings may be only 10% to 20%.

How the federal statutory definition of interchangeability will mesh with state pharmacy laws dealing with substitution also remains to be seen. “A lot of this doesn’t make sense to the average person,” added Koeller. “Apparently, you have to be a government employee to figure it out.”

The patents of several major biologics are projected to expire in the next 5 years. However, because of the uncer-

Multidisciplinary Review Team: Include a Lawyer Because of the nature of these products, a team that includes pharmacists and physicians will be needed for biosimilar review—a systematic review process that examines product, manufacturing, and institutional and patient factors. Rather than having 20 people who can never find the time to meet, Koeller suggested a core group of committee members, bringing in experts as needed on a product-by-product basis.

“This group needs to be multidisciplinary in membership,” said Koeller. “It needs to include pharmacists, physicians, nurses, businessmen, and lawyers.”

One of the P&T committee’s powers is the ability to deem a biosimilar interchangeable, even if that drug has yet to be deemed so by the FDA’s terminology.

An institutional formulary committee can establish therapeutic interchange for products with a similar efficacy and safety profile, even if those products

dence >10%) were headache, abdominal pain, diarrhea, dizziness, fatigue, pruritus, dyspnea, and muscle spasms.

Overall, 4% of patients discontinued

medication for these genetic mutations before administering ramucirumab.

Earlier in the year, the FDA approved ramucirumab alone and in combina-

Jim Koeller, MS

are chemically or structurally different.

However, Koeller advised exercising caution when making therapeutic interchangeability decisions based on biosimilar data. “You can deem anything interchangeable,” he said. “You just assume the risk.”

“How similar is similar enough to be defined as highly similar when it comes to a complex biologic?”

Jim Koeller, MS

“Put a risk manager and lawyer on your committee immediately,” said Koeller. “If we do this and there’s an issue, does your center want to take the liability? The whole reason for doing this is economic savings. Why make the change if you can’t save money?” l Reference

Koeller J. Implementing a biosimilars review panel at your institution. Presented at: Association of Community Cancer Centers 31st National Oncology Conference; October 8-10, 2014; San Diego, CA.

FDA UPDATE Jakafi Gets New Indication for Use in Patients with Polycythemia Vera The FDA approved ruxolitinib (Jakafi; Incyte Corporation) for the treatment of patients with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea. The FDA approval was based on Protocol CINC424B2301, a multicenter, open-­label, active-control trial of 222 patients with PV whose disease was resistant to or who were intolerant of hydroxyurea. The composite end point was durable hematocrit control and spleen volume reduction, and a durable hematocrit control that obviated the need for regular phlebotomy. Patients were randomized to ruxo­ litinib 10 mg twice daily (N = 110) or to best available care (N = 112).

Ruxolitinib was superior to best available therapy in durable hematocrit control and in spleen volume reduction at week 32 (21% vs 1%; P <.001) and at week 48 (19% vs 1%; P <.001), as well as in a relatively high rate (55%) of durable hematocrit control at week 48.

The most common hematologic adverse reactions (incidence >20%) through week 32 were thrombocytopenia and anemia. The most common nonhematologic adverse events (inci-

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FEBRUARY 2015 I VOL 8, NO 1

In patients with EGFR or ALK mutations, disease progression should be considered for treatment with an FDA-approved medication for these genetic mutations before administering ramucirumab. therapy with ruxolitinib because of adverse events. (December 14, 2014) Cyramza Approved in Combination with Docetaxel for Metastatic NSCLC Ramucirumab (Cyramza; Eli Lilly) received a new indication for use in combination with docetaxel for the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) whose disease is progressing with or after platinum-based chemotherapy. In patients with EGFR or ALK mutations, disease progression should be considered for treatment with an FDA-approved

tion with paclitaxel for the treatment of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma after disease progression while using first-line therapy.

The approval of ramucirumab in combination with docetaxel for patients with NSCLC was based on results of the multicenter, double-blind, placebo-­ controlled study of 1253 patients with previously treated metastatic NSCLC that showed improved overall survival (OS). Patients were randomized to ramucirumab in combination with docetaxel on day 1 of a 21-day cycle (N = 628) or to placebo plus

docetaxel (N = 625). The median OS was 10.5 months in the ramuciru­mab plus docetaxel arm and 9.1 months in the placebo plus docetaxel arm, a significant difference (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.98; P = .024). Progression-free survival (PFS) was also significantly longer with ramucirumab than with placebo (HR, 0.76; 95% CI, 0.68-0.86; P <.001).

Among 1245 patients who received at least 1 dose of ramucirumab plus docetaxel, the most frequent adverse reactions (incidence ≥30%) were neutropenia, fatigue/asthenia, and stomatitis/mucosal inflammation. The most common serious adverse reactions with the active combination were febrile neutropenia (14%), pneumonia (6%), and neutropenia (5%).

(December 12, 2014) Cyramza plus Paclitaxel for Advanced Gastric Cancer After Chemotherapy The FDA approved ramucirumab­­ (Cyramza; Eli Lilly) in combination with­ paclitaxel for patients with advanced or metastatic gastric cancer or with GEJ adenocarcinoma whose cancer has progressed while receiving or after flu­­

www.TheOncologyPharmacist.com

LUNG CANCER

Effective Lung Cancer Screening Meg Barbor

“T

here’s a lot we don’t know about lung cancer screening,” according to Denise Aberle, MD, who spoke at the recent American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research. However, certain measures can be taken to lower false-positive and overdiagnosis rates, lessen costs, ameliorate patient suffering, and correctly identify screening cohorts, she asserted.

Who Should Be Screened?

The National Lung Screening Trial (NLST) recommends lung cancer screening for adults aged 55 to 74 years who have at least a 30 pack-year smoking history and currently smoke or have quit within the past 15 years.

The US Preventive Services Task Force (USPSTF) has the same screening criteria, but has made revisions based on the Cancer Intervention and Surveillance Modeling Network (CISNET) models that are funded by the National Cancer Institute; they have extended the screening period

up to individuals aged 80 years and do not recommend screening for individuals who have not smoked within the past 15 years.

“Many others have recommended that we use risk prediction models to try to better hone in on those individuals who should be screened...

[However] using these risk predictors practically can be somewhat problematic.”

Denise Aberle, MD

The CISNET models that informed the USPSTF recommendations consist of 5 different consortiums, each having independent models for lung can-

cer, explained Dr Aberle, Vice Chair of Research and a Professor in the Department of Radiological Science and Professor of Bioengineering at the University of California, Los Angeles.

“When they looked across these 5 models they found a mortality reduction of anywhere from 8% to 24%.

About half who went through screening had early-stage disease, and it is estimated that up to 500 per 100,000 lung cancer deaths across the population could be averted with the gain in life years,” she said.

“Many others have recommended that we use risk prediction models to try to better hone in on those individuals who should be screened,” said Dr Aberle. Their premise is that we determine a threshold below which individuals will not be screened, and that doing so will improve on the existing NLST criteria. However, “using these risk predictors practically can be somewhat problematic,” she added.

What Can Be Done About FalsePositivity Rates?

The false-positivity rate was one of

the major limitations of the NLST, said Dr Aberle. Consequences of this in a screening setting include addi-

key points

➤ The NLST recommends lung cancer screening for adults aged 55-74 years with a smoking history of ≥30 pack-years who currently smoke or have quit within the past 15 years ➤ The false-positivity rate was one of the major limitations of the NLST ➤ Overscreening results in unnecessary imaging, radiation exposure, and biopsies and the potential complications and additional costs ➤ Although some lung tumors will grow over time, others will regress, and there is insufficient knowledge about lung cancer to support screening decisions Continued on page 12

FDA UPDATE oropyrimidine- or platinum-containing­­ chemotherapy. In April, ramucirumab­ was approved as monotherapy for ad­­ vanced or metastatic gastric cancer or GEJ adenocarcinoma.

This new approval was based on the RAINBOW study, a phase 3 clinical trial that compared ramucirumab plus paclitaxel versus placebo plus paclitaxel.

Ramucirumab plus paclitaxel significantly extended median OS at 9.6 months compared with 7.4 months (P = .017) with placebo plus paclitaxel. Furthermore, ramucirumab plus paclitaxel significantly delayed disease progression: the PFS was 4.4 months with the active combination versus 2.9 months (P <.001) with placebo plus paclitaxel. Overall, 28% of patients responded to ramucirumab plus paclitaxel versus 16% with placebo plus paclitaxel (P <.001).

The FDA approved this new therapy with a boxed warning regarding the risk for bleeding, including severe and sometimes fatal hemorrhaging.

Ramucirumab injection should be permanently discontinued in patients with severe bleeding.

The most common adverse reactions in the trial with the active combination and ≥2% higher than in the placebo group were fatigue, neutropenia, diar-

rhea, and epistaxis. The most common serious adverse events with ramuciru­ mab plus paclitaxel were neutro­ penia (3.7%) and febrile neutropenia (2.4%); furthermore, 19% of patients receiving the active combination had to receive granulocyte colony-stimulating factors.

(November 5, 2014) Blincyto First Immunotherapy Approved for B-Cell Acute Lymphoblastic Leukemia The FDA approved blinatumomab (Blincyto; Amgen) for the treatment of patients with relapsed or refractory Philadelphia chromosome (Ph)-negative precursor B-cell acute lymphoblastic leukemia (ALL), a rare and rapidly growing form of ALL. Blinatumomab is intended for use in patients with B-cell ALL. Blinatumomab is the first immunotherapy approved by the FDA for patients with leukemia. The drug acts as a connector between the CD19 protein (which is found on the surface of most B-cell lymphoblasts) and the CD3 protein found on T-cell lymphocytes, using the body’s T-cells to destroy the leukemia cells.

The FDA had initially granted this drug a breakthrough therapy designa-

tion, and applied its priority review and accelerated approval program to approve the drug 5 months ahead of the scheduled date. Blinatumomab has an orphan drug designation. The FDA is now requiring the manufacturer to conduct a new clinical trial to show a survival benefit with blinatumomab in patients with relapsed or refractory

The approval was based on the safety and efficacy of blinatumomab in a clinical trial of 185 adults with Ph-negative relapsed or refractory precursor B-cell ALL. Ph-negative precursor B-cell ALL. The approval was based on the safety and efficacy of blinatumomab in a clinical trial of 185 adults with Ph-negative relapsed or refractory precursor B-cell ALL. All patients received an infusion of blinatumomab for at least 4 weeks.

The results showed a 32% complete

remission rate lasting approximately 6.7 months. The trial was not designed to show improvement in survival.

Blinatumomab is associated with significant risks, including cytokine release syndrome, encephalopathy, and nervous system adverse events.

The most common side effects reported were pyrexia, headache, peripheral edema, febrile neutropenia, nausea, hypokalemia, fatigue, constipation, diarrhea, and tremor.

Blinatumomab was approved with a Risk Evaluation and Mitigation Strategy program to inform healthcare providers about the serious risks associated with this medication. The product information also carries a boxed warning to alert providers of the risks and serious side effects associated with the use of blinatumomab. (December 3, 2014) Avastin plus Chemotherapy for Platinum-Resistant Gynecologic Cancers The FDA approved a new indication for bevacizumab solution (Avastin; Genentech) to be used in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for the treatment of patients with platinum-resisContinued on page 12

www.TheOncologyPharmacist.com

FEBRUARY 2015 I VOL 8, NO 1

11

LUNG CANCER

Effective Lung Cancer Screening... Continued from page 11 tional unnecessary imaging and radiation exposure, unnecessary biopsies and the complications of those biopsies, unnecessary anxiety, and additional cost, she explained.

According to Dr Aberle, if we look only at the published data from the NLST and stratify the nodules that factored into positive screens over each of the screening intervals, we can see that nodules that were ≤6 mm amounted to more than half of positive screenings but were responsible for less than 1% of lung cancers overall; if we look at increasing nodule size, the positive predictive value goes up so that the larger the nodule, the more likely it is that the person has cancer.

“This gives us a clue that size is important and might help us determine whether or not a screen is significant,” she suggested. “If we look at small nodules, 4-5 mm, we see that if we did nothing with those nodules but simply saw them one year later, we would suffer trivial effects with respect to the ability to diagnose lung cancer.”

When Is It Overdiagnosis?

“I understand the terms of overdiagnosis, and I understand the concept of overdiagnosis; I think where I stumble

“I understand the terms of overdiagnosis, and I understand the concept of overdiagnosis; I think where I stumble is when I look at the notion of overdiagnosis in the individual patient setting.”

Denise Aberle, MD

is when I look at the notion of overdiagnosis in the individual patient setting,” said Dr Aberle. Questions concerning overdiagnosis are constantly raised, she noted. “But the only question for which there is a resounding

answer is ‘we cannot assume a linear growth model.’”

“Some of these cancers are going to get worse over time, even over long periods of time. Some of these cancers are going to stay just the way they were. Some of these lesions may actually regress,” she noted. “We just don’t know enough and I think it makes it challenging to make these kinds of decisions in the individual patient setting.”

Next Steps in Screening Dr Aberle stated that it will behoove society to measure risk in individuals who are screened, redefine actionable nodules to lower false positives, maintain low radiation doses using current multidetector scanners, track smoking cessation efforts and rates, and collect the data via screening centers.

“Only in that way will we begin to understand what risk-to-benefit ratios are in the population setting and how we can maximize cost effectiveness,” she said.

“There’s a lot we don’t know about lung cancer screening; I personally

find that exciting because I want to be able to help answer some of those questions,” she added. l Reference

Aberle DR. Lung cancer screening: from efficacy to effectiveness. Presented at: 13th Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research; September 28-October 1, 2014; New Orleans, LA.

WANT TO PARTICIPATE IN TOP’S NEW POLL? See page 4 for details.

FDA UPDATE Continued from page 11

tant, recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

The approval is based on the results of the AURELIA study, an international, randomized trial with investigator-assessed PFS. AURELIA compared bevacizumab plus chemotherapy versus chemotherapy alone. Overall, 179 patients were randomized to bevaciz­ umab plus chemotherapy and 182 patients received chemotherapy alone with 1 of the 3 chemotherapies.

Treatment continued until disease progression, unacceptable toxicity, and/ or consent withdrawal. All the patients had received ≤2 previous chemotherapy regimens, had ECOG performance status of 0 to 2, and had disease recurrence within <6 months of the platinum-based therapy.

Bevacizumab plus chemotherapy had a significant PFS improvement compared with chemotherapy alone (HR, 0.38; 95% CI, 0.30-0.49; P <.001), with a median PFS of 6.8 months versus 3.4 months, respectively; however, the OS was not significantly different, with a median OS of 16.6 months versus 13.3 months, respectively (HR, 0.89; 95% CI, 0.69-1.14).

The most common adverse reactions (≥15%) with bevacizumab plus chemotherapy were neutropenia, peripheral

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FEBRUARY 2015 I VOL 8, NO 1

sensory neuropathy, and hypertension.

Gastrointestinal perforations were reported in 1.7% of patients who received bevacizumab. (November 14, 2014) FDA Approves Nivolumab for Advanced Melanoma The FDA recently approved nivolu­ mab (Opdivo; Bristol-Myers Squibb Company), a human programmed

who received the drug. This response lasted for >6 months in approximately one-third of the patients. The 32% ORR (95% CI, 23-41) was based on data from 4 patients (3%) who achieved a complete response and 34 patients (28%) who achieved a partial response.

Efficacy of the drug was evaluated during a planned, interim, single-arm

The approval is based on the results of the AURELIA study, an international, randomized trial with investigator-assessed PFS. death receptor-1 blocking antibody, for the treatment of patients with unresectable or metastatic melanoma that no longer responds to ipilimumab. The drug was also approved for the treatment of patients with melanoma with a BRAF V600 mutation that no longer responds to ipilimumab and BRAF inhibitor therapy.

The FDA accelerated its approval of nivolumab based on interim data from the CheckMate 037 phase 3 trial showing a 32% (N = 38) objective response rate (ORR) in the first 120 patients

analysis of data from the phase 3, randomized, open-label CheckMate 037 trial. A total of 268 patients received the 3-mg/kg intravenous dose every 2 weeks; patients in the comparator arm (N = 102) received an investigator’s choice of chemotherapy: single-agent dacarbazine or a combination of carboplatin plus paclitaxel. The primary objectives in this trial are ORR and OS. The study is ongoing but no longer recruiting patients.

The most common adverse reaction reported among patients receiving the

study drug was rash (21%). Grade 3/4 adverse reactions occurred in 42% of the patients receiving the study drug. The most frequent of these—reported in 2% to <5% of patients receiving the study drug—were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase.

The FDA granted breakthrough therapy designation, priority review, and orphan product designation for nivolumab because (1) preliminary clinical evidence demonstrated that the drug may offer a substantial improvement over available therapies; (2) the drug has the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition; and (3) the drug is intended to treat a rare disease, respectively.

“Opdivo is the seventh new melanoma drug approved by the FDA since 2011,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The continued development and approval of novel therapies based on our increasing understanding of tumor immunology and molecular pathways are changing the treatment paradigm for serious and life-threatening diseases.” (December 22, 2014) l

www.TheOncologyPharmacist.com

SIDE EFFECTS MANAGEMENT

Novel Agent Effective for the Management of Cancer-Related Cachexia Phoebe Starr

C

ancer-related cachexia is a debilitating condition that has had no effective treatment thus far.

Its symptoms include loss of lean body mass, as well as muscle wasting and loss of appetite.

A pair of pivotal international phase 3 studies suggest that the investigational oral drug anamorelin hydrochloride can increase lean body mass, achieve weight gain, and improve quality of life (QOL). This drug is the first to hold promise for improving all of these aspects of cancer-related cachexia.

“Cachexia is one of the most troubling symptoms of cancer for patients and their families. This is a very exciting study. For the first time in more than a decade, a drug is effective in treating cachexia. This will significantly change how we think about cancer­ -related cachexia and how we treat patients with cancer,” said study coauthor David Currow, MD, of Flinders University in Adelaide, Australia.

Treatment with anamorelin may enable patients to continue with their cancer treatment, he said. Dr Currow discussed these results at a press conference during the 2014 Congress of the

European Society for Medical Oncology.

Jennifer Temel, MD, of the DanaFarber Cancer Institute in Boston, MA, presented the results in an oral session at the congress. “Cancer-related cachexia-­ anorexia causes progressive functional

“Cachexia is one of the most troubling symptoms of cancer for patients and their families.

This is a very exciting study. For the first time in more than a decade, a drug is effective in treating cachexia. This will significantly change how we think about cancer-related cachexia and how we treat patients with cancer.”

David Currow, MD

impairment, inactivity, and can negatively impact prognosis. Current treatment options have limited efficacy and potential risks, especially in patients with cachexia,” Dr Temel told listeners.

Anamorelin is a first-in-class, orally administered ghrelin receptor agonist.

Release of ghrelin stimulates multiple pathways that regulate body weight, lean

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body mass, appetite, and metabolism.

ROMANA 1 (N = 484) and RO­­ MANA 2 (N = 495) were identically designed phase 3 studies, representing the largest phase 3 trials conducted to date to assess the safety and efficacy of

anamorelin in patients with cachexia.

Patients with stage III or IV unresectable non–small-cell lung cancer and cancer-related cachexia were randomized 2:1 to receive either anamorelin or placebo for 12 weeks. All patients enrolled in the trials had a life expectancy of >4 months.

For study purposes, cachexia was defined as ≥5% weight loss within the past 6 months or a body mass index <20 kg/m2. At the end of 12 weeks, patients had the option to continue on anamorelin for an additional 12 weeks, and those results (ROMANA 3) will be presented at a later date.

Dr Temel noted that the studies had broad inclusion criteria. Patients could be on chemotherapy, maintenance chemotherapy, or no chemotherapy.

In both ROMANA 1 and ROMANA 2, patients randomized to placebo continued to lose weight and lean body mass over the 12-week study period, whereas those randomized to anamorelin gained weight and lean body mass.

The difference between the 2 groups for lean body mass and body weight increases was highly significant in both trials (P <.0001 for all comparisons).

The study failed to show an improvement in handgrip strength, which was a coprimary end point.

QOL (a secondary end point) was assessed, in part, by the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire, which looks at patient symptoms and concerns related to anorexia-cachexia, including appetite, early satiety, and general health. In both trials, a significant difference was observed between the 2 treatment arms on the FAACT

anorexia/cachexia domain at all time points, favoring anamorelin treatment over placebo. Results for QOL in this domain were slightly more robust for ROMANA 1 (P = .0012) than for ROMANA 2 (P = .0150). Patients were followed for 1 year for survival.

Rates of toxicity related to anamo­ relin were low. The most common adverse events included nausea, hyperglycemia, and a few cases of diabetes.

“These are incredibly exciting results.

The benefits are consistent. Up until

key points

➤ Cancer-related cachexia is a debilitating condition associated with loss of lean body mass, muscle wasting, and loss of appetite ➤ There are currently no effective treatments for the symptoms of cachexia ➤ The investigational drug anamorelin, a first-in-class, orally administered ghrelin receptor agonist, has shown promising results for this condition ➤ In this new study, anamorelin was associated with “exciting results,” in affecting lean body mass in patients with cancerrelated cachexia, and was associated with low toxicity

now you couldn’t change lean body mass in patients with cancer-related cachexia. This therapy has the potential to affect cancer therapy across all treatment centers,” Dr Currow said.

The formal discussant of this trial, Florian Scotté, MD, of Georges Pompidou European Hospital in Paris, France, commended the authors on a well­-designed study for a condition with few good treatment options.

He pointed out that other studies of new agents have had disappointing results. “I look forward to hearing the long-term follow-up on these patients.

This is a difficult problem, and we have to pay full attention to this, working with a multidisciplinary approach,” Dr Scotté said. l Reference

Temel J, Currow D, Fearon K, et al. Anamorelin for the treatment of cancer anorexia-cachexia in NSCLC: results from the phase 3 studies ROMANA 1 and 2.

Presented at: 2014 Congress of the European Society for Medical Oncology; September 26-30, 2014; Madrid, Spain. Abstract 1483O_PR.

FEBRUARY 2015 I VOL 8, NO 1

13

SYMPTOM MANAGEMENT

Symptom Management Drives Value in Oncology Continued from cover suffering. So we knew we had to treat these symptoms early,” Ms Graze said.

Untreated symptoms cost payers too.

“We knew that if a patient has to go to the ED [emergency department] for oncology symptom management, they have a better than 50% chance of being admitted,” said Ms Graze. “So we really wanted to alleviate these [symptoms] with earlier care for our patients.”

Despite this incentive, establishing the symptom management clinic was not easy. Lack of standardized assessment tools, equipment, digital support, and staffing issues all posed barriers. Perhaps the biggest obstacle, Ms Graze said, was psychological.

“Systematic nursing assessments with interventions lead to better quality of life for patients.”

Lynn Graze, RN, MSN, OCN

“Patients do not like to bother their physicians….The communication of symptoms during office visits is flawed compared with concurrent diaries of symptoms; what patients document as their symptoms is not what they’re telling their physicians.”

Accurate patient assessment is critical to cost-savings by providing the right care at the right time and place, with fewer dose modifications. The symptom management model was developed with the patient perspective in mind. “We needed to find a way to make care easier for the patients,” said Ms Graze. “We wanted to get to symptoms early, treat them, and keep patients out of the ED….Patient education was critical.”

Run by nurse practitioners (NPs) and triage nurses, the clinic provides rapid access and coordination of care with the oncologists and infusion team. If 1 of 19 criteria is met, a patient can automatically be put on the NP’s schedule. Triage phone lines are answered by infusion nurses and average between 70 and 100 calls daily.

“We didn’t extend the clinic hours,” said Barry R. Meisenberg, MD, Chair for Quality Improvement and Healthcare Systems Research, Anne Arundel Medical Center. “We just made it easier to reach us during clinic hours.”

Significant Results A study conducted by the hospital showed good results for the symptom management clinic in the first 8 months.

14

FEBRUARY 2015 I VOL 8, NO 1

Overall, 41 patients were seen monthly in the clinic for pain, anorexia, nausea, vomiting, diarrhea, swelling, and fever. Of these, 65% of patients were seen the same day and 25% were seen the following day.

Emergency department visits went from 26 to 17 monthly, a 35% reduction.

“We didn’t invent symptom management. There’s probably a description of this in Homer with the Greek army and the gates of Troy….What we were able

to do was embed the SMC within the larger oncology clinic, and we achieved a 35% reduction in ED visits,” said Dr Meisenberg.

He said the study proved that a significant percentage of non–chemotherapy-related admissions could be prevented with little effort, without overhauling the oncology care model.

“We have to expand the concepts so we’re taking care of not only the patients

on our clinic schedules, but the patients who are not on our clinic schedule. We basically need an alternative roster of patients that we’re managing via the phone and the triage,” Dr Meisenberg emphasized.

“The financial incentive is there, and we can make the case to our payers that this is important for us to do for more than one reason. It’s also good patient care,” he concluded. l

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WEALTH MANAGEMENT

8 Prescriptions to Improve Your Finances Andrew D. Schwartz, CPA, and Lawrence B. Keller, CFP, CLU, ChFC, RHU, LUTCF Mr Schwartz is a partner in the Boston CPA firm Schwartz & Schwartz, P.C. Mr Keller is the founder of Physician Financial Services.

W

hy is financial planning important? The term financial planning can be used to illustrate many things. It can be a comprehensive plan, focusing on several needs or goals simultaneously, or limited to specific areas such as establishing a budget, or saving for a home, a child’s education, or retirement. A comprehensive financial plan serves as a framework for organizing your financial life. One of the main benefits of a financial plan is that it can help you balance competing financial priorities by clearly showing you how your financial goals are related, and how decisions made in one area subsequently affect the others.

What Steps Can You Take?

Here are some prudent steps you can take to keep personal finances heading in the right direction: 1. Reset your retirement savings.

Most people find it easier to maximize their retirement plans by depositing a fixed dollar amount each month or a percentage of their salary. Instruct your employer to withhold enough each month for your 401(k) or 403(b) plan to ensure reaching the maximum contri­ bution of $17,500 in 2014. Are you self-employed? If so, you can contribute up to $52,000 annually into a Simplified Employee Pension (SEP), Keogh, or Solo 401(k) plan for 2014. In addition, if you are aged 50 years or older by December 31, 2014, the maximum contribution increases to $23,000 for 401(k) and 403(b) salary deferrals, and $57,500 for Solo 401(k) plans.

2. Refinance your home. You’ve heard about the record-low interest rates. You may want to lower your monthly mortgage payment by refinancing to a lower interest rate or to a shorter loan term (eg, from a 30-year mortgage to a 15-year mortgage), allowing you to own your home in a shorter period of time. You may want to refinance your adjustable rate mortgage (ARM) to a fixed-rate mortgage or a new ARM with better terms. Finally, another option would be to refinance in order to take cash out of your home or simply use your home equity for home improvements, to pay for college, or to reduce or consolidate existing debt.

3. Reduce your student loan debt.

Unfortunately, many healthcare professionals who could be eligible to refinance student loan debt are not aware that the option exists. Most borrowers tend to “set and forget” student loans, choosing a repayment plan after graduation and never taking a second look. The problem with this approach is that their rate

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remains the same throughout the life of the loan, even as their financial situation improves and they potentially become eligible for a lower rate. As its name suggests, consolidating implies combining multiple student loans into 1 loan.

However, the word can have different implications depending on whether it refers to federal or private student loans.

Federal student loan consolidation is offered by the government and is available for most types of federal loans (no private loans allowed). After the loans are combined, the resulting interest rate is a weighted average of the original loan rates, which means the borrower does not effectively save any money.

Similar to federal consolidation, a private consolidation loan allows a borrower to combine multiple loans into 1.

However, the resulting interest rate is not a weighted average of the original loan rates. Instead, a private lender will typically use the borrower’s credit score and other relevant financial information

Lawrence B. Keller

al or financial catastrophe such as divorce or disability. If all goes well and none of these scenarios materialize, then you will be left with a wonderful choice: retire earlier or retire wealthier.

5. Rebalance your investment portfolio. Warren Buffett said it best by stating, “A simple rule dictates my buying: Be fearful when others are greedy, and be greedy when others are fearful.”

During 2013, the stock market posted substantial gains. By rebalancing your portfolio to its original or updated asset allocation, you lock in gains from the sectors that performed the best and move money into sectors that underperformed and soon enough should be poised to catch up.

6. Recalculate how much your retirement savings will be worth when you retire. Take a look at how much buying power you can expect to have at retirement. Be sure to download the online retirement calculator (www.mdtaxes.com) to find out what your savings will really be worth when you retire.

One of the main benefits of a financial plan is that it can help you balance competing financial priorities by clearly showing you how your financial goals are related.

to give him a new interest rate and loan, then use that loan to pay off the original loans. Essentially, consolidating loans with a private lender is the same thing as refinancing those loans. Not all student loan refinance lenders are alike. When comparing private lenders to determine where to refinance, borrowers should consider the interest rates, flexibility, and additional benefits available. Social Finance, Inc and Darien Rowayton Bank are examples of private lenders.

Important disclosure and repayment information for SoFi refinance loans can be viewed on their website at www.SoFi. com.

4. Revise your savings and debt reduction goals. Take a few minutes to set new savings goals. Ideally, pharmacists, physician assistants, and nurse practitioners should save 15% to 20% of their gross income toward retirement. While it is true that if you start early you can save less, saving 15% to 20% provides flexibility for years where you might not be able to save as much, to allow for poor investment returns, or for a person-

7. Revisit your disability and life insurance needs. Throughout your career and life, disability and life insurance needs change. Give some thought to how much of these insurances you need versus how much you currently receive through your employer.

As a healthcare professional, the ability to earn an income is your most valuable asset. For this reason, you should purchase an individual noncancelable, guaranteed renewable “own-occupation” disability insurance policy with benefits payable to the age of 65 years or longer, a residual disability rider, a costof-living adjustment rider, and a future increase option rider. This type of policy will provide you with income if you are disabled and cannot perform your duties as a pharmacist, physician assistant, or nurse practitioner—even if you choose to work in another occupation. Be sure to look for a policy with a “multilife” or association discount. While this can provide men with a savings of 10% to 15% off of their policies, women can save as much as 60% off of their polices

if a gender neutral or “unisex” rate is available.

Term life insurance is for the most part a commodity, so the pricing is very competitive and comparison shopping is easy. Websites such as www.term4 sale.com can compare the premium rates of several insurance companies and various death benefit amounts and guarantee periods. You should employ the services of an experienced insurance agent who represents several companies to help you get the best rates, especially if your health is less than perfect. The agent will know which carriers are likely to provide a better underwriting classification based on your height and weight, immediate family history, and/or other medical issues to allow you to secure a lower premium rate. For example, if you have an immediate family (mother, father, brother, sister) history of cancer, certain companies will allow you to qualify for their best underwriting classification while others will not. As your financial situation changes, you can reevaluate the amount and type of insurance you own. A good general rule of thumb is to insure yourself for 7 to 10 times your gross income.

Purchase automobile, homeowner’s/ renter’s, and umbrella (“excess liability”) policies. These policies will protect you and/or your assets, and future earnings. Make sure your deductible is at least $1000 and that the liability limits of your automobile and homeowner’s insurance match. In addition, if they are all with the same company, substantial discounts may be available.

8. Resolve errors on your credit report. Each year, you are entitled to 3 free credit reports, so there is no excuse not to look at this important financial report annually, especially since errors are common. If you find information that is outdated, incorrect, or misleading upon review, you should contact the credit reporting agency as soon as possible. If the disputed data are found to be incorrect, the lender or information provider must notify all credit reporting agencies nationwide to correct the information in your file. If the negative information proves to be correct, you still have the right to insert a brief commentary (100 words) about the entry on your credit report. Order your free report at www. annualcreditreport.com.

Conclusion Make sure that your plan is up to date.

It is also possible that you will need to modify your plan due to changes in your personal circumstances or the economy.

These 8 steps are a great place to start. l

FEBRUARY 2015 I VOL 8, NO 1

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The publishers of The Oncology ® Pharmacist , are proud to

present our 3rd annual Conquering the Cancer Care Continuum™ series.

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Good Manufacturing Practice Lillie D. Shockney, RN, BS, MAS

University Distinguished Service Associate Professor of Breast Cancer Johns Hopkins University School of Medicine, Baltimore, MD

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nions express VA © 2014 Gr ed are from . TEVA provided the een Hill He the authors althcare Co and not nec idea for this article mmunication essarily tho se of TEVA s, LLC .

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CONFERENCE NEWS

Cancer Drug Pricing in the United States: What Is Driving the High Costs?

Wayne Kuznar

San Francisco, CA—The cost of medical innovation, in particular, a fair price for new cancer medicines, is a complex topic that requires urgent attention, said speakers at a special symposium at the 2014 American Society of Hematology meeting. The financial burden imposed by cancer treatments, and how best to reduce this burden without compromising patient outcomes, generated heated exchanges. Some charged that the price tag of new cancer drugs does not match the clinical benefit. Others emphasized the impact on patients as reducing outcomes.

US Market Shoulders Bigger Cost Burden Three new drugs approved by the FDA for the treatment of chronic myeloid leukemia (CML) cost approximately $100,000 annually, or almost 5 times the cost of imatinib (Gleevec) in 2001. Before 2000, the average cancer drug price was from

The US taxpayers subsidize most of the research and development in cancer.

“Ironically, when drugs are approved, US patients and the healthcare system pay 50% to 200% more than the rest of the world on comparable drugs.”

Hagop M. Kantarjian, MD

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$5000 to $10,000 annually. By 2005, the increase was between $30,000 and $50,000 annually, and then ≥$100,000 by 2012, observed Hagop M. Kantarjian, MD, Professor of Medicine and Chairman, Department of Leukemia, M.D. Anderson Cancer Center, Houston.

Of the 13 drugs approved by the FDA in 2012 for cancer indications, 13 were priced at ≥$100,000 annually. Even older drugs are increasing in price at a rate of 10% to 20% annually. The price for imatinib increased from $28,000 in 2001 to $92,000 in 2012.

“The explanation is that the industry can charge what the market bears,” said Dr Kantarjian. In addition, the US taxpayers subsidize most of the research and development in cancer, he noted.

“Ironically, when drugs are approved, US patients and the healthcare system pay 50% to 200% more than the rest of the world on comparable drugs,” Dr Kantarjian said.

In addition, the pharmaceutical companies claim that it now costs $1 billion to research, develop, and bring to market a cancer drug. Dr Kantarjian suggested that this is not the case, saying that the revised estimate is that the actual cost is 5% to 20% of that cost estimate, which amounts to $60 million to $170 million.

High Costs Affect Patient Outcomes The end result, Dr Kantarjian noted, is the financial harm to patients— high rate of personal bankruptcies, and emotional and socioeconomic adverse effects on patients and their families. Overall, 10% of patients with cancer do not take their medications, and 20% are poorly adherent.

This adversely affects survival rates, he said.

In CML, for example, the 10-year relative survival rate in Sweden is 80% compared with a 5-year survival rate of only 60% in patients with CML in the United States, based on SEER data. Despite this disparity in survival, patients in the United States have a 30% higher cost of treatment.

Patients have “skin in the game,” Dr Kantarjian said. The key question, he added, “is what our patients can afford.”

When it comes to cancer drugs, out-ofpocket (OOP) costs are not affordable for many patients.

In part, the reason that US patients pay more is the vast number of lobbyists for the pharmaceutical industry,

said Dr Kantarjian. The lack of patient advocates keeps drug prices high in the United States, he argued. “Even elected officials appear to represent interest groups,” he said. “Only patients are patient advocates.” It will take a

they are dying and are humiliated,” he said.

According to Mr Bastian, drug pricing reflects American-style capitalism.

“Alternative pricing models are very difficult to implement.”

“In one study, equipping patients with understandable information on the burden of costs of cancer care reduced OOP costs in 57% of cases, without requiring a change in the treatment regimen.”

S. Yousuf Zafar, MD, MHS

patient-based grassroots movement to reverse the tide.

Market Forces Drive Drug Costs Alex W. Bastian, MBA, of GfK Market Access, San Francisco, argued that practical market forces drive drug cost, as with other commodities. The high cost is an “unintended consequence” of continued investment in drug research by the private market.

“What is the US getting for these higher prices? Broader access to new medicines than other countries have,” Mr Bastian said.

He noted that spending on cancer treatment accounts for approximately 6% of all healthcare spending, which is lower in the United States than in Europe. Rising costs are a global phenomenon, and rising healthcare spending is not an isolated US phenomenon.

Between 1998 and 2014, a total of 249 hematologic cancer drugs were unsuccessful, which creates a huge burden on pharmaceutical companies.

“The market may fix itself; it always has….Natural mechanisms provide balance to the system, and one of these is loss of exclusivity” (ie, patent expirations), he added.

Dr Kantarjian countered that a drug purchase by a patient is not a business transaction. “We are talking about a population who did everything right, including buying insurance, and now

Greater Transparency Can Improve Outcomes The cost of paying for cancer impacts the efficacy of treatment, agreed S. Yousuf Zafar, MD, MHS, Assistant Professor, Division of Medical Oncology, Duke Cancer Institute, Durham, NC. High patient cost burden is associated with a 70% higher likelihood of nonadherence to treatment.

Improving transparency may be one way to empower patients and improve outcomes, said Dr Zafar. He described his prospective study in which equipping patients with understandable information on the burden of costs of cancer care reduced OOP costs in 57% of cases, without requiring a change in the treatment regimen.

Responding to the suggestion that prices must be high to fuel progress and innovation in drug development, he said, “Making progress in the long run is not a reason for prices to be at the profiteering level.”

Dr Zafar introduced the concept of financial toxicity in oncology into patient care, calling on all oncologists to discuss cost issues with their patients to enhance outcomes and reduce pain.

See article in the November 2014 issue of Value-Based Cancer Care (www. valuebasedcancer.com/vbcc-issues/ 2014/november-2014-vol-5-no-9/25781financial-toxicity-beginning-to-gainoncologists-attention-finally). l

FEBRUARY 2015 I VOL 8, NO 1

17

BEST PRACTICES

Addressing Patient Safety for Oral Chemotherapy Continued from cover “We have created a safe environment for IV chemotherapy, but we need to extend the safety of parenteral chemotherapy to oral chemotherapy,” she stated.

“Oral chemotherapy has unique challenges,” Krzyzanowska continued.

“There are new prescribers and community pharmacists filling prescriptions. Data suggest they have little training and experience to dispense these medications. Oral chemotherapy changes the roles for existing caregivers and increases the responsibility for patients and caregivers while reducing responsibility among oncologists.”

“Oral chemotherapy changes the roles for existing caregivers and increases the responsibility for patients and caregivers while reducing responsibility among oncologists.”

Monika Krzyzanowska, MD, MPH, FRCPC

The benefits versus harm of oral chemotherapy need to be considered.

It is possible that oral chemotherapy could have decreased efficacy because of incorrect prescribing, underadherence, and drug/food interactions, as well as an increased risk because of

incorrect prescribing, overadherence, and drug/food interactions, she said.

“We have done a good job with parenteral chemotherapy regarding setting prescribing standards, preprinted orders, dispensing in a controlled environment, safe handling, and standardized assessment for follow-up. But the situation for oral drugs is different,” Krzyzanowska stated.

By contrast, restrictions on who can prescribe oral chemotherapy are few, and there is variable use of computerized physician order entry or preprinted orders, lack of standardization in education, poor-quality educational materials, and lack of education for new “players.” Dispensers of oral chemotherapy are a mixture of community and cancer pharmacies, and community pharmacies have minimal verification standards and few if any safety checks. Also, there are no standardized processes and effective tools for monitoring patients on oral chemotherapy.

Moving forward to address these gaps, Krzyzanowska commended the joint ASCO/ Oncology Nursing Society updated prescribing standards that now include guidelines for oral chemotherapy.2 However, more effort is needed to implement these standards, she told the audience, noting that a small study suggests that implementing them reduces prescribing errors by two-thirds.

More education is needed about oral chemotherapy, she continued, including clarifying the roles of dispensers, identifying effective approaches and tools, and training providers as

well as evaluating the effectiveness of such training. She suggested that audience members review a teaching tool about oral chemotherapy developed by the Multinational Association of Supportive Care in Cancer.3 “The area of dispensing probably needs the most attention for patient safety,” she said.

Dispensing standards are needed, and dispensers should be educated about safe handling and chemotherapy verification.

Dispensing standards are needed, and dispensers should be educated about safe handling and chemotherapy verification. She suggested limiting those who can dispense oral chemotherapy within the cancer clinic.

Recommendations for safe handling of oral chemotherapy should be developed for manufacturers, healthcare providers, patients, and caregivers.

Policies and procedures are needed for monitoring patients on oral chemotherapy. “We need to identify effective tools, assess effectiveness, and promote incident reporting,” Krzyzanowska noted.

Many methods are available for measuring adherence, such as self-reports, medication diaries, and pill count. But few studies have evaluated adherence

tools specifically for oral chemotherapy.

“I would recommend that you ask your patients about whether they are taking their oral medicines and whether there are issues. You might be surprised what you find,” she advised.

Key ingredients for optimizing adherence include regular assessments, counseling and education, individualized monitoring plans, reminders to take medications (eg, pill boxes, alarms, smartphone applications, text messages).

“We need to learn from experience about which methods work and which ones don’t. Bring the lessons you learn to meetings and share with your colleagues,” she said.

“The next frontier is oral chemotherapy support programs, specialized clinics, and telephone support. Think about your own practice and hospital and the biggest gaps. Figure out which ones to address first. I suggest you start with safe prescribing, leverage existing guidelines, metrics, and lessons from previous initiatives; remember to evaluate the impact of these measures, and don’t be afraid to innovate,” Krzyzanowska concluded. l References

1. Krzyzanowska M. Extending the quality & safety agenda from parenteral to oral chemotherapy. Presented at: ASCO Quality Care Symposium; October 17-18, 2014; Boston, MA. 2. Neuss MN, Polovich M, McNiff K, et al. 2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy. J Oncol Pract. 2013;9(suppl 2):5s-13s.

3. Kav S, Schulmeister L, Nirenberg A, et al.

Development of the MASCC Teaching Tool for Patients Receiving Oral Agents for Cancer. Support Care Cancer. 2010;18:583-590.

TAKE ACTION: GET YOUR CANCER CENTER PROFILED! We are looking to interview oncology pharmacists from cancer centers around the country. It’s an easy process—a short phone interview and you need to submit some photos.

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FEBRUARY 2015 I VOL 8, NO 1

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IMMUNOTHERAPY

World Cutaneous Malignancies Congress

T

he Third Annual World Cutaneous Malignancies Congress (WCMC) took place in San Francisco, CA, on October 30-31, 2014. The WCMC is a 2-day congress dedicated to informing, educating, and fostering the exchange of clinically relevant information in the field of cutaneous malignancies on topics in melanoma, basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), and cutaneous T-cell lymphoma (CTCL). The following articles highlight proceedings regarding immunotherapies in oncology. For additional highlights from this premier meeting, visit www.cutaneousmalignancies.com.

Targeted Agents, Immunotherapy, and Other Treatments Are Emerging for Cutaneous Malignancies Malignant Melanoma Interferon remains the adjuvant therapy of choice in patients at high risk for recurrence of malignant melanoma, said Reinhard Dummer, MD.1 A systematic review favored high-dose interferon versus observation on relapse-free survival but not overall survival (OS) in patients with high-risk resected primary melanoma. Recently, however, relapse-free survival was found to be a surrogate end point for OS in a meta-analysis of 12 adjuvant trials in patients with resectable melanoma.2 Ulceration and stage are predictive of interferon efficacy in melanoma, such that “only patients with ulceration and microscopic [N1] disease are profiting from pegylated interferon alfa-2b,” said Dummer, vice chairman, Department of Dermatology, University Hospital Zürich, Switzerland. Two years of treatment with interferon in the adjuvant setting is warranted, he said.

For high-risk melanoma patients with macrometastases (N1b disease and higher), interferon has a minor impact, but adjuvant ipilimumab after surgery offers an improvement in recurrence-free survival, said Dummer. Specifically, in the EORTC 18071 trial, 3-year recurrence-free survival rates were 46.5% in patients randomized to ipilimumab (10 mg/kg every 3 weeks for 4 doses) versus 34.8% in a placebo group—a 25% relative reduction in risk with ipilimumab. Median recurrence-free survival was 26.1 months in the ipilimumab group and 17.1 months in the placebo group (P = .0013). The impact on recurrence-free survival with ipilimumab was observed in patients with microscopic metastases (33% risk reduction) and with macroscopic metastases (17% risk reduction). About half of the patients discontinued ipilimumab because of side effects, most within the first 16 weeks.

Basal Cell Carcinoma In the treatment of advanced BCC, the hedgehog pathway is already being targeted with the smoothened inhibitor vismodegib, said Aleksandar Sekulic, MD, PhD, associate professor of dermatology at the Mayo Clinic campus in Scottsdale, AZ.3 “There are several points in the hedgehog pathway where one can potentially intervene,” he said.

www.TheOncologyPharmacist.com

Smoothened is a G-protein–coupled receptor protein encoded by the SMO gene of the hedgehog pathway. Other potential targets in the pathway are at the level of hedgehog binding to patched or downstream of smoothened at the level of the Gli protein. In addition to vismodegib, smoothened inhibitors in development are sonidegib (phase 2), LEQ506 (phase 1), BMS-833823 (phase 1/2), TAK-441 (phase 1), IPI-926 (phase 1/2), and PF-04449913 (phase 1).

“There are several points in the hedgehog pathway where one can potentially intervene.”

Aleksandar Sekulic, MD, PhD

Vismodegib was associated with overall response rates of 30% in metastatic BCC and 43% in locally advanced BCC in the pivotal phase 2 trial.4 Responses with sonidegib in a phase 2 trial were comparable. In Gorlin syndrome, vismodegib significantly reduced the diameter of existing BCCs, and the number of new BCCs compared with placebo.5 An open-label trial of neoadjuvant vismodegib followed by Mohs surgery was associated with a 31% decrease in the anticipated surgical defect among patients who completed 3 months of treatment; results from a phase 2 placebo-controlled trial are pending.

Vismodegib plus radiation therapy is being studied in a phase 2 trial of patients with locally advanced BCC. Cutaneous T-Cell Lymphoma Brentuximab vedotin is a chimeric anti-CD30 monoclonal antibody linked to monomethyl auristatin E, a synthetic antitubulin agent, which is being studied in CD30-positive CTCL. Response rates in the range of 70% were obtained with brentuximab vedotin across the spectrum of baseline CD30 expression in patients with mycosis fungoides (MF) or Sézary syndrome (SS) stage IB to IVB, said Steven Horwitz, MD.6 Lower disease stage predicted better response in this study.

Median CD30max was higher in responders to brentuximab vedotin compared with nonresponders (15.5% vs 3.0%; P = .037), and those with CD30 expression <5% were less likely to respond than those with CD30 expression ≥5% (P <.005).

The CCR4 receptor, present in all stages of CTCL, is another target, said Horwitz, associate attending physician, Memorial Sloan Kettering Cancer Center, New York City. KW-0761 (mogamulizumab) is a monoclonal antibody with enhanced antibody-­ dependent cellular cytotoxicity compared with conventional antibodies. A phase 1/2 study in patients with previously treated CTCL, including MF and SS, showed good tolerability and an overall response rate of 42%. A phase 3 study is comparing progression-free survival in patients randomized to KW-0761 or vorinostat in patients with relapsed/refractory CTCL. IPI-145 is a potent oral inhibitor of both the PI3K-δ and PI3K-γ isoforms that inhibits malignant B- and T-cell survival. Early evidence suggests singleagent activity of IPI-145 in CTCL and peripheral T-cell lymphoma.7

“It is a soft drug that is active in skin and breaks down to inactive metabolites.”

Steven Horwitz, MD

The anti–PD-L1 monoclonal antibody MPDL3280A targets PD-L1 on antigen-presenting cells or tumor cells and prevents interaction with PD-1 on T cells; it has shown encouraging clinical activity in MF/CTCL. A phase 2 study with the anti–PD-1 monoclonal antibody MK-3745 in CTCL (MF/SS) is opening, said Horwitz.

Histone deacetylase (HDAC) has a role in modulating cellular pathways such as proliferation, apoptosis, migration, and differentiation. Adverse effects limit the use of systemic HDAC inhibitors. SHP-141 is a topically applied HDAC inhibitor that inhibits isoforms 1, 2, 3, and 6. “It is a soft drug that is active in skin and breaks down to inac-

tive metabolites,” he said. In a phase 1b study in early-stage CTCL, SHP141 applied to index lesions produced a clinical objective response (>50% improvement by CAILS) in 28%.8 Merkel Cell Carcinoma Cytotoxic chemotherapy works well early in MCC, but the response is short-lived. MCC may be too aggressive for immunotherapy, but targeted therapies may be beneficial, said Shailender Bhatia, MD.9 Because MCC is a neuroendocrine tumor, there appears to be a role for targeting the somatostatin receptor with a somatostatin analog. A trial of pasireotide in MCC and melanoma is ongoing.

Single-fraction high-grade (8 Gy) radiation therapy has been effective with rapid onset of palliation and minimal toxicity in MCC, said Bhatia, assistant professor of medical oncology, University of Washington, Seattle.

Single-fraction high-grade radiation is potentially immunogenic and is convenient for patients who are located far from a radiation facility. l References

1. Dummer R. Changing arena of adjuvant therapy in malignant melanoma. Presented at: Third Annual World Cutaneous Malignancies Congress; October 30-31, 2014; San Francisco, CA. 2. Suciu S, Eggermont AM, Lorigan P, et al. Relapsefree survival (RFS) as a surrogate endpoint for overall survival (OS) in adjuvant interferon trials in patients (pts) with resectable cutaneous melanoma: an individual patient data (IPD) meta-analysis. Presented at: 2014 Congress of the European Society for Medical Oncology; September 26-30, 2014; Madrid, Spain.

Abstract 1089PD. 3. Sekulic A. Ongoing clinical studies in BCC. Presented at: Third Annual World Cutaneous Malignancies Congress; October 30-31, 2014; San Francisco, CA. 4. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma.

N Engl J Med. 2012;366:2171-2179.

5. Tang TY, Mackay-Wiggan JM, Aszterbaum M, et al. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012;366:2180-2188.

6. Horwitz S. New systemic therapies in CTCL: beyond the old paradigms. Presented at: Third Annual World Cutaneous Malignancies Congress; October 30-31, 2014; San Francisco, CA. 7. Horwitz S, Flinn I, Patel MR, et al. Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with relapsed/refractory lymphoma. Presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31-June 4, 2013; Chicago, IL. Abstract 8518.

8. Kim YH, Krathen M, Duvic M, et al. A phase 1b study in cutaneous T-cell lymphoma (CTCL) with the novel topically applied skin-restricted histone deacteylase inhibitor (HDAC-i) SHP-141. Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract 8525.

9. Bhatia S. Emerging treatment options in MCC: chemotherapy and alternative approaches for metastatic disease. Presented at: Third Annual World Cutaneous Malignancies Congress; October 30-31, 2014; San Francisco, CA.

Continued on page 20

FEBRUARY 2015 I VOL 8, NO 1

19

IMMUNOTHERAPY

New Drugs and Clinical Trial Data: Updates in Cutaneous...

I

mmune-targeted therapies and in­­ hibitors of hedgehog pathway signaling dot the landscape in recent investigations in the treatment of patients with melanoma, BCC, and MCC. A rundown of findings with newly approved therapies and investigational therapies was presented at the Third Annual World Cutaneous Malignancies Congress.

Immune Therapies in Melanoma In the treatment of patients with advanced melanoma, anti–PD-1 monoclonal antibodies have proved effective as single agents. Pembrolizumab is a humanized high-affinity antibody that exerts dual ligand blockade of PD-1; nivolumab is a fully human monoclonal antibody that is also directed toward PD-1. These anti–PD-1 antibodies represent breakthroughs in extending survival, said Caroline Robert, MD, PhD.1 They perform similarly in the setting of advanced melanoma, with an objective response rate (ORR) of 32% to 34% and 1-year OS in excess of 60%. “Five years ago, only 25% to 30% of patients were still alive at 1 year,” she said.

“The study represents the largest planned, prospective, observational cohort study of patients with advanced BCC and BCNS.” Jean Y. Tang, MD, PhD

In patients with ipilimumab-refractory advanced melanoma, pembrolizu­ mab at 2 or 10 mg/kg was associated with an ORR of 26% and a disease control rate of 50%.

The phase 3 CA209-037 study evaluated nivolumab versus investigator’s choice of chemotherapy (ICC) in 405 patients with advanced melanoma who had progressed despite previous therapies directed against CTLA-4 or BRAF mutation.2 Interim efficacy analysis showed a higher ORR in patients who received nivolu­­ mab therapy compared with ICC (32% vs 11%), with 3 complete responses in the nivolumab group. Ninety-five percent in the nivolumab group had ongoing response with a minimum of 24 weeks of follow-up, said Robert, head of dermatology at the Institut Gustave Roussy, Paris. Responses with nivolumab were observed regardless of

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FEBRUARY 2015 I VOL 8, NO 1

pretreatment PD-L1 expression status, BRAF mutation status, or prior benefit from anti–CTLA-4 therapy.

The most recent advancement in the treatment of advanced melanoma is combining ipilimumab and nivolu­ mab. Blocking these pathways represents an immunotherapy strategy that can restore tumor-specific T-cell–mediated immunity. In a phase 1 clinical study, the combination given concurrently was associated with an ORR of 40% and survival of 85% at 1 year and 79% at 2 years. Even better 1-year (94%) and 2-year survival (88%) was achieved when they were given sequentially.3 Treatment responses were independent of BRAF mutation status. Almost two-thirds (64%) of patients had grade 3/4 treatment-related adverse events.

Registry Examining Real-World Management of Advanced Basal Cell Carcinoma The real-world management of advanced BCC is being examined in the RegiSONIC Disease Registry Study, said Jean Y. Tang, MD, PhD.4 The goal of RegiSONIC is to learn how clinicians determine and treat advanced BCC in the real world by evaluating the effectiveness, safety, and use of systemic and local treatments in 3 BCC populations: (1) advanced BCC patients who do not have basal cell nevus syndrome (BCNS) and are naive to treatment with a hedgehog pathway inhibitor; (2) those who were previously enrolled in a trial of the hedgehog pathway inhibitor vismodegib; and (3) patients who have BCNS advanced BCC or who have multiple nonadvanced, hedgehog pathway–naive BCC. “The study represents the largest planned, prospective, observational cohort study of patients with advanced BCC and BCNS,” said Tang, associate professor of dermatology at Stanford University in California. It is attempting to provide real-world data that will inform the medical community and improve the care of patients with advanced BCC. RegiSONIC is a multicenter, prospective, observational cohort study in adult patients with advanced BCC or BCNS and per-protocol follow-up.

The determination of advanced BCC is left to the discretion of the study clinician, and treatment, procedures, and clinic visit schedules are left to the clinician’s discretion in accordance with routine practice.

Based on the first 131 locally advanced BCC patients enrolled, locally advanced BCC appears to be determined by using a number of tumor

characteristics, including size (74%), extent (61%), and location (62%).

Median size of the locally advanced BCC was 20.5 mm at determination, the most frequent location was the nose (19.8%), and the most common histopathology was nodular (58.8%).

The pivotal molecular abnormality in BCC carcinogenesis is inappropriate activation of the hedgehog signaling pathway. “Essentially all BCC tumors have an overactive hedgehog signaling pathway, commonly occurring by mutational inactivation of the tumor suppressor PTCH1 gene,” she said.

“The combination of itraconazole and arsenic trioxide does an even better job of reducing tumor size.”

Jean Y. Tang, MD, PhD

Vismodegib is a small-molecule inhibitor of the hedgehog signaling pathway that has been proved effective in the treatment of locally advanced BCC. Significant ORRs with vismodegib are observed in both locally advanced and metastatic BCCs, and the clinical response to vismodegib in responders frequently occurs in a matter of weeks, said Tang.

Vismodegib appears to be an effective chemopreventive agent for BCC. Tang and colleagues showed prevention of new BCCs in patients with BCNS.5 Other data show that in operable BCC, neoadjuvant vismodegib reduces the surgical defect size by 27% at an average of 4 months of treatment.

Patients must be on neoadjuvant treatment for at least 3 months to see this effect, said Tang, and they should be counseled about the significant side effects associated with the drug.

Managing Resistance to Hedgehog Inhibitor More than half of patients with advanced BCCs develop resistance to vismodegib. In these patients, the hedgehog pathway becomes reactivated; 50% of resistant BCCs contain mutations in the SMO gene of the hedgehog pathway.

Smoothened inhibitors as second-line therapy may be effective when resistance to vismodegib develops, said Tang.

Itraconazole reduces hedgehog pathway signaling by 50% in vismodegib-naive tumors, and reduced BCC tumor size by 20% at 1 month of therapy. In the mouse model, “the combination of itraconazole and arsenic trioxide does an even better

Continued from page 19

job of reducing tumor size,” she said. In a small sample of 5 patients, the combination was shown to reduce hedgehog signaling as well.

Immunotherapy Approaches in Merkel Cell Carcinoma The use of immunotherapy in MCC is rational, given the increased incidence of the disease and the worse prognosis in immunocompromised patients, “suggesting that the immune system is important in controlling the disease,” said Isaac Brownell, MD, PhD.6 In addition, prognosis of MCC is improved with the presence of CD8+ tumor-infiltrating lymphocytes. There are documented cases of spontaneous regression of MCC attributed to an antitumor immune response; responses have been observed with immune-stimulating therapies such as dinitrochlorobenzene, tumor necrosis factor-alpha, and interferon, and 80% of MCC patients express non-self Merkel cell polyomavirus viral antigens. Also, the prognosis of MCC is improved with high titers of MCV VP1.

“Similar observations predicted the immune responsiveness of melanoma,” said Brownell, head, Cutaneous Development and Carcinogenesis Sec­ tion, Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Active immunotherapy trials for MCC include the following agents: anti–PD-L1, adoptive T cells, interleukin (IL)-12 plasmid in vivo electroporation DNA vaccine, glucopyranosyl lipid adjuvant-stable emulsion, F16-IL2 antibody-cytokine fusion with paclitaxel, and adjuvant ipilimumab for excised MCC. l References

1. Robert C. Anti-PD-1 antibodies ± ipilimumab in melanoma. Presented at: Third Annual World Cutaneous Malignancies Congress; October 30-31, 2014; San Francisco, CA. 2. Weber JS, Minor DR, D’Angelo S, et al. A phase 3 randomized, open-label study of nivolumab (antiPD-1; BMS-936558; ONO-4538) versus investigator’s choice chemotherapy (ICC) in patients with advanced melanoma after prior anti-CTLA-4 therapy. Presented at: 2014 Congress of the European Society for Medical Oncology; September 26-30, 2014; Madrid, Spain.

Abstract LBA3_PR. 3. Kluger H, Sznol M, Callahan M, et al. Survival, response duration, and activity by BRAF mutation (MT) status in a phase 1 trial of nivolumab (antiPD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). Presented at: 2014 Congress of the European Society for Medical Oncology; September 26-30, 2014; Madrid, Spain. Abstract 1085O. 4. Tang J. Real-world management of BCC: the RegiSONIC study. Presented at: Third Annual World Cutaneous Malignancies Congress; October 30-31, 2014; San Francisco, CA. 5. Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012;366:2180-2188.

6. Brownell I. Rationale and status of immune targeted therapies for MCC. Presented at: Third Annual World Cutaneous Malignancies Congress; October 30-31, 2014; San Francisco, CA.

www.TheOncologyPharmacist.com

HODGKIN LYMPHOMA

Posttransplant Brentuximab: New Standard of Care for Hodgkin Lymphoma?

Phoebe Starr

San Francisco, CA—Early posttransplant consolidation with brentuximab vedotin (Adcetris) significantly improved progression-free survival (PFS) compared with placebo in patients with Hodgkin lymphoma

who are at risk for disease progression in the placebo-controlled phase 3 AETHERA trial. AETHERA is the first placebo-­ controlled trial to compare brentuximab and placebo in patients with Hodgkin lympho-

ma after transplant. The results of the study were presented at the 2014 American Society of Hematology annual meeting.

The median PFS was 43 months for the group receiving brentuximab

Innovations in Oncology Management

TM

A newsletter series for oncology practice administrators, administrative staff, advanced practice clinicians, and oncology pharmacists.

The series will provide concise, up-to-date information on current issues that are impacting the business of oncology.

versus 24 months for the group receiving placebo (P = .001), representing a 43% reduction in the risk for disease progression. The 2-year PFS rates were 65% and 45%, respectively, for the cohorts.

“In my opinion, once this study is published, brentuximab should be the standard of care for patients with risk factors for disease progression,” namely, with remission duration <1 year, extranodal disease, B symptoms, 2 or more previous salvage therapies, and primary refractory disease,” stated lead investigator Craig H. Moskowitz,

“In my opinion, once this study is published, brentuximab should be the standard of care for patients with risk factors for disease progression.”

Craig H. Moskowitz, MD

Good Manufacturing Process

MD, Clinical Director, Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, New York. Dr Moskowitz called the 20% difference in 2-year PFS “unprecedented” in any lymphoma.

Autologous stem-cell transplant (ASCT) cures approximately 50% of patients with relapsed or refractory Hodgkin lymphoma. The other 50% will relapse after transplant. Before this study, no investigational regimen had improved posttransplant outcomes.

Brentuximab is an antibody-drug conjugate directed to CD30, which is typically expressed in classic Hodg­kin lymphoma cells. Although brentuximab has been approved by the FDA for the treatment of relapsed or refractory Hodgkin lymphoma and for systemic anaplastic large-cell lymphoma, it is not approved for posttransplant consolidation.

Topics include: Part 1: Patient Support Services Part 2: Oral Parity Legislation Part 3: Emerging Payment and Delivery Models Part 4: Working Collaboratively with Local Payers TO VIEW THE SERIES ONLINE PLEASE LOG ON TO:

InnovationsInOncologyManagement.com anagement.com Supported by funding from Celgene Corporation and Celgene Patient Support. Manufacturer did not influence content.

EHC388 Innovations ASize_120214

Study Details The international multicenter trial enrolled 329 patients with Hodgkin lymphoma who had at least 1 risk factor for relapse. Approximately 50% of the patients had ≥3 risk factors for disease progression at baseline. After ASCT, patients were randomized to Continued on page 22

www.TheOncologyPharmacist.com

FEBRUARY 2015 I VOL 8, NO 1

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CANCER CENTER PROFILE

St. Joseph’s/Candler Health System In addition, I am responsible for coordinating approval of all chemotherapy regimens ordered for the system—both inpatient and outpatient.

I also run an outpatient chemotherapy specialty pharmacy, and I teach and precept students for 3 different colleges of pharmacy. I work with students during their last year of the doctoral program, providing Advanced Pharmacy Practice Experience.

Nancy M. Nix, PharmD, BCPS, BCOP

giving patients the opportunity to access advances in treatment and research that would otherwise not be available in their community.

The Oncology Pharmacist spoke with Nancy M. Nix, PharmD, BCPS, BCOP, coordinator of oncology clinical pharmacy services for St. Joseph’s/Candler, and of ambulatory infusion and retail pharmacy services located on Hilton Head Island, SC. We asked her about the various “hats” she wears.

What are your job responsibilities?

Nancy M. Nix (NMN): I am the oncology pharmacy clinical coordinator for the entire St. Joseph’s/Candler Health System. Even though I am responsible for day-to-day patient care at the Hilton Head Island infusion practice, electronic communication allows me to coordinate despite geographic separation.

My first responsibility is to the outpatients at my ambulatory infusion center.

We treat between 15 and 40 patients per day, both oncology and nononcology patients. For example, we give intravenous infusions to nononcology anemia patients and to patients with osteoporosis.

What are some of the challenges and rewards of your work?

NMN: My biggest challenge is not having enough time. Also, I have a strong belief that people should not be stagnant, so I am always assigning to myself and my students projects that stretch us beyond our presumed capabilities. I am very invested in being educated and providing education. I enjoy being challenged.

My biggest rewards depend on which “hat” I am wearing. Regarding patient care, I feel rewarded whenever I can counsel patients and help provide a level of comfort and understanding about their treatment. I want my patients to feel cared for and to know there is someone looking over them.

Regarding my work with students, I feel rewarded when they are able to accomplish something beyond their expectations on day 1. For example, I recently helped a student through the process of writing a journal article by breaking it down step-by-step so that she was able to complete this article within 4 weeks and submit it for publication. I’d like to think she learned to overcome perceived limitations to benefit her as she continues her career.

As clinical coordinator, I am rewarded whenever I program a new order set into the electronic health records. Doing this is a huge process. We have several hun-

Continued from cover

dred order sets and many new approvals.

Oncology is an ever-changing specialty—probably the most changing medical specialty there is today.

What are you excited about in your job?

NMN: I have collaborated with Unlimited Systems in Cincinnati, OH, to develop a software program called Looking Glass. This program documents at the time of compounding all National Drug Code numbers, lot

actually dispensed to the patient in order to reimburse.

We have been using this software for 13 months, and several other oncology centers have adopted it as well.

What advice would you give to a person entering the field of oncology pharmacy?

NMN: Find a good mentor. I had 3 different mentors who influenced me, inspired me, and challenged me. The first 2 showed me that oncology doesn’t have

“My biggest challenge is not having enough time. Also, I have a strong belief that people should not be stagnant, so I am always assigning to myself and my students projects that stretch us beyond our presumed capabilities. I am very invested in being educated and providing education. I enjoy being challenged.” numbers, and expiration dates of compounded products for administration at our center using barcode scanning and technology.

Is this an advance? Why is this needed?

NMN: Looking Glass grew out of limitations I saw in our software. I expressed my concern to the folks at Unlimited Systems about inadequate software not suited for clinical use.

This led to a collaboration with them to develop the software program.

Looking Glass was developed as a companion product to document our dispensing records, as well as to permit chair-side scanning of barcoded products. Many insurance companies require documentation of what was

to be depressing. The third one taught me how to use available resources to stay current with oncology information and to participate in specialty listservs.

He encouraged me to spend at least 30 minutes every day reading to learn what is new, and changing, in oncology.

What would you do if you won the lottery?

NMN: First I would homeschool my 8-year-old daughter and travel with her to different countries to study other cultures. That would take up about another 10 years. Then if I still had unlimited funds, I would devote my energies to helping children who don’t have sufficient encouragement, good parenting, or resources to go beyond their limitations. Maybe I would be a missionary. l

HODGKIN LYMPHOMA

16 cycles of treatment with brentuximab or placebo. Of patients in the placebo group who progressed, 85% were crossed over to brentuximab.

Brentuximab achieved superior PFS in all prespecified subgroups, including primary refractory patients who relapsed within 12 months of frontline therapy and patients who relapsed after 12 months with extranodal disease.

The overall survival (OS) was no different between the 2 treatment arms in the interim analysis at 2 years,

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FEBRUARY 2015 I VOL 8, NO 1

© American Society of Hematology. All rights reserved.

Posttransplant Brentuximab: New Standard of Care...

“Brentuximab achieved superior PFS in all prespecified subgroups, including primary refractory patients who relapsed within 12 months of frontline therapy.”

Craig H. Moskowitz, MD

Continued from page 21

which could be attributed to the high percentage of patients receiving placebo who crossed over to the active treatment arm. The final OS analysis will be presented in 2016.

The most common adverse events in the brentuximab arm included peripheral sensory neuropathy (56%), neutropenia (35%), upper respiratory tract infection (26%), fatigue (24%), and peripheral motor neuropathy (23%).

Dose reductions of brentuximab effectively alleviated peripheral neuropathy in the majority of patients. l

www.TheOncologyPharmacist.com

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In melanoma…

A T CELL IS ONLY AS EFFECTIVE 1 AS THE ANTIGEN THAT ACTIVATES IT T cell

Dendritic cell

Tumor-derived antigens (TDAs) set the immune system in motion by priming and activating T cells. Once released, TDAs are processed by dendritic cells and subsequently presented to T cells, initiating an adaptive immune response.1-3 Learn more at

MelanomaAntigens.com

References: 1. Kaufman HL, Disis ML. J Clin Invest. 2004;113:664-667. 2. Klebanoff CA, Gattinoni L, Restifo NP. Immunol Rev. 2006;211:214-224. 3. den Boer AT, van Mierlo GJD, Fransen MF, Melief CJM, Offringa R, Toes REM. J Immunol. 2004;172:6074-6079. ©2014 Amgen Inc. All rights reserved. 8/14 USA-678-100568