TON December 2013 by The Oncology Nurse

DECEMBER 2013

www.TheOncologyNurse.com

VOL 6, NO 11

OVARIAN CANCER

CANCER CENTER PROFILE

Scripps Cancer Center— Stevens Division at Scripps Memorial Hospital Meeting the Needs of Patients

Antiangiogenesis Pursued in High-Risk Ovarian Cancer Alice Goodman

ngiogenesis is an active area of clinical research in ovarian cancer, but proving that this approach extends overall survival (OS) has been somewhat challenging thus far. Michael Bookman, MD, reviewed studies of antiangiogenesis in highgrade serous ovarian cancer at the 2013 Chemotherapy Foundation Symposium, held in New York City. Bookman is the director of medical oncology at the University of Arizona Cancer Center in Tucson.

“High-grade serous ovarian cancer is the most common subtype of epithelial ovarian cancer and it remains highly lethal. New approaches are needed beyond angiogenesis,” he told listeners. “The key questions to consider in antiangiogenic trials are the best targets, the preferred strategy, and the optimal setting for these studies,” Bookman said. “We need predictive biomarkers and we need to think about how we measure success in clinical trials.” Continued on page 8

THE PATIENT’S VOICE Some of the team at the Scripps Cancer Center—Stevens Division (left to right): Paula Thomas, Eileen Gaudette, Janine Rodriguez, Cathleen Sugarman, and Jaime Malone.

he Scripps Cancer Center—Stevens Division is located at Scripps Memorial Hospital in La Jolla, California, and is part of the San Diego County–wide Scripps Health cancer care network. The center is committed to working with cancer patients from diagnosis through treatment. As 1 of only 2 Integrated Network Cancer Programs in California (as designated by the American College of Surgeons), Scripps Health encompasses the oncology resources of 5 hospital campuses, a broad network of cancer care specialists and affiliated physicians, and the renowned Scripps research professionals. In addition to providing a full continuum of cancer care for patients, the center offers cancer prevention and early detection services and access to educational and social support services.

The Other Side of the Stethoscope Tania Homonchuk, MD

am 60 years old and an ovarian cancer survivor. I’m also an emergency department doctor who usually is treating people, making diagnoses, and being the one in charge. However, much the same as most women with ovarian cancer, my diagnosis came out of the blue with minimal symptoms at an advanced stage. I found myself for once on the other side, as a patient. I’m happy to say that I am now 2½ years disease-free from my last treatment in January 2011. The start of my story is in 2009. I

NEWS BRIEFS Alice Goodman

he field of ovarian cancer is an active area of research, with a number of potential approaches showing promise in improving outcomes. Targeted therapies have made advances in this disease, and experts are learning how best to exploit these. A selection of news high-

lights on ovarian cancer, from the European Cancer Congress (ECCO/ ESMO/ESTRO), the Chemotherapy Foundation Symposium, and the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, follows.

Continued on page 16

INSIDE

Continued on page 30

Ovarian Cancer in the News

was working full time in the emergency department with the usual 8- to 12-hour shifts of days, evenings, and nights. That year I was pretty busy working in both Sacramento and San Diego, keeping up with one son in college and his rowing regattas, and another son who was a junior in high school, active in sports and with college applications coming up. In 2010 I scaled back to working just in San Diego with a perfect number of shifts, more time at home, working out more,

OVARIAN CANCER

Neoadjuvant Chemotherapy a Reasonable Option for Advanced Ovarian Cancer . . . . . . . . . . . . . . . . . . . . .

THROUGH THE EYES OF AN ADVOCATE. . . . . . . . . . . . . . . . . . . . . . . .

Important Steps in the Conquest of Ovarian Cancer

Resources for Patients, Survivors, Providers, Researchers, and Supporters. . . . . . . . . . . . . . . . . . . . . . . .

YOU VOTED FOR

EMPOWERING PATIENTS AND SURVIVORS. . . . . . . . . . . . . . . . . . . . . . .

ONE Award

A Thrust Into Vulnerability

The 2013

Find out who won on page 28

Take a bite out of G-CSF acquisition costs*

*Based on wholesale acquisition cost (WAC) of all short-acting G-CSF products as of November 11, 2013. WAC represents published catalogue or list prices and may not represent actual transactional prices. Please contact your supplier for actual prices.

Indication » GRANIXTM (tbo-filgrastim) Injection is a leukocyte growth factor indicated for reduction in the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Important Safety Information » Splenic rupture: Splenic rupture, including fatal cases, can occur following the administration of human granulocyte colony-stimulating factors (hG-CSFs). Discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture in patients who report upper abdominal or shoulder pain after receiving GRANIX.

» Acute respiratory distress syndrome (ARDS): ARDS can occur in patients receiving hG-CSFs. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS.

» Allergic reactions: Serious allergic reactions, including anaphylaxis, can occur in patients receiving hG-CSFs. Reactions can occur on initial exposure. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim.

NOW AVAILABLE

GRANIX is a new option in short-acting G-CSF therapy TM

» GRANIX demonstrated a 71% reduction in duration of severe neutropenia (DSN) vs placebo1 – GRANIX significantly reduced DSN when compared to placebo (1.1 days vs 3.8 days; p<0.001)1 – Efficacy was evaluated in a multinational, multicenter, randomized, controlled, Phase III study of chemotherapy-naïve patients with high-risk breast cancer receiving doxorubicin (60 mg/m2 IV bolus)/docetaxel (75 mg/m2)1

» Safety was evaluated in 3 Phase III clinical trials1

Important Safety Information (continued) » Use in patients with sickle cell disease: Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving hG-CSFs. Consider the potential risks and benefits prior to the administration of GRANIX in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis.

» Potential for tumor growth stimulatory effects on malignant cells: The granulocyte colonystimulating factor (G-CSF) receptor, through which GRANIX acts, has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded.

» Most common treatment-emergent adverse reaction: The most common treatment-emergent adverse reaction that occurred in patients treated with GRANIX at the recommended dose with an incidence of at least 1% or greater and two times more frequent than in the placebo group was bone pain.

Please see brief summary of Full Prescribing Information on adjacent page. For more information, visit GRANIXhcp.com. Reference: 1. GRANIX TM (tbo-filgrastim) Injection Prescribing Information. North Wales, PA: Teva Pharmaceuticals; 2013.

NOTEWORTHY NUMBERS

Ovarian Cancer On November 3, Freedom Plaza in Washington, DC, was an emotional center of activity as the third annual National Race to End Women’s Cancer began and ended there. The Foundation for Women’s Cancer, established by the Society of Gynecologic Oncologists, sponsors the event to raise awareness and research funds for all gynecologic cancers. Ovarian cancer, which has the highest mortality of the gynecologic cancers, is our focus this month.

Annually, there are more than 22,000 new cases of ovarian cancer in the United States, represent-

ing only 1.3% of all new cancer diagnoses; however, more than 186,000 women are currently esti-

BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR GRANIX™ (tbo-filgrastim) Injection, for subcutaneous use SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE GRANIX is indicated to reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Splenic Rupture Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture. 5.2 Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS. 5.3 Allergic Reactions Serious allergic reactions including anaphylaxis can occur in patients receiving human granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may reduce the severity of the reactions. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim. 5.4 Use in Patients with Sickle Cell Disease Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis. 5.5 Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte colony-stimulating factor (G-CSF) receptor through which GRANIX acts has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded. 6 ADVERSE REACTIONS The following potential serious adverse reactions are discussed in greater detail in other sections of the labeling: • Splenic Rupture [see Warnings and Precautions (5.1)] • Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.2)] • Serious Allergic Reactions [see Warnings and Precautions (5.3)] • Use in Patients with Sickle Cell Disease [see Warnings and Precautions (5.4)] • Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions (5.5)] The most common treatment-emergent adverse reaction that occurred at an incidence of at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group was bone pain. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. GRANIX clinical trials safety data are based upon the results of three randomized clinical trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of patients were female, the median age was 50 years, and 86% of patients were Caucasian. In the lung cancer study, 80% of patients were male, the median age was 58 years, and 95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients were male, the median age was 55 years, and 88% of patients were Caucasian. In all three studies a placebo (Cycle 1 of the breast cancer study only) or a nonUS-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of ≥10,000 x 106/L after nadir was reached. Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the

mated to be living with ovarian cancer, and 14,000 women die of this disease each year.1

recommended dose and was numerically two times more frequent than in the placebo group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-US-approved filgrastim product). Leukocytosis In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies. 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving GRANIX has not been adequately determined. 7 DRUG INTERACTIONS No formal drug interaction studies between GRANIX and other drugs have been performed. Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies of GRANIX in pregnant women. In an embryofetal developmental study, treatment of pregnant rabbits with tbo-filgrastim resulted in adverse embryofetal findings, including increased spontaneous abortion and fetal malformations at a maternally toxic dose. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In the embryofetal developmental study, pregnant rabbits were administered subcutaneous doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day. Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day. This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC0-24) of approximately 50-90 times the exposures observed in patients treated with the clinical tbo-filgrastim dose of 5 mcg/kg/day. 8.3 Nursing Mothers It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GRANIX is administered to a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. 8.4 Pediatric Use The safety and effectiveness of GRANIX in pediatric patients have not been established. 8.5 Geriatric Use Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients were 65 years of age and older. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients. 8.6 Renal Impairment The safety and efficacy of GRANIX have not been studied in patients with moderate or severe renal impairment. No dose adjustment is recommended for patients with mild renal impairment. 8.7 Hepatic Impairment The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment. 10 OVERDOSAGE No case of overdose has been reported.

©2013 Cephalon, Inc., a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. GRANIX is a trademark of Teva Pharmaceutical Industries Ltd. Manufactured by: Sicor Biotech UAB Vilnius, Lithuania U.S. License No. 1803 Distributed by: Teva Pharmaceuticals USA, Inc. North Wales, PA 19454 Product of Israel FIL-40045 July 2013 This brief summary is based on TBO-003 GRANIX full Prescribing Information.

DIGITAL

A combination of heat and doxorubicin delivered with nanotechnology can kill up to 95% of ovarian cancer cells.2 Researchers at Oregon State University have developed and evaluated a new treatment for drug-resistant ovarian cancer by which engineered iron oxide nanoparticles act as a delivery system for doxorubicin and also heat cancer cells remotely when the particles are exposed to an alternating magnetic field. For women with ovarian cancer, treatment by a gynecologic oncologist yields significantly better surgical results and overall survival, and women who receive appropriate treatment are 34% less likely to die. In the United States, however, more than 60% of patients with ovarian cancer do not receive the correct therapy.3 Sources 1. http://seer.cancer.gov/statfacts/html/ovary.html. 2. http://ir.library.oregonstate.edu/xmlui/handle/1957/ 43046. 3. http://awomanshealth.com/what-every-womanshould-know-about-gynecologic-cancer/.

www.TheOncologyNurse.com

DECEMBER 2013 I VOL 6, NO 11

724-37388

Of women diagnosed with ovarian cancer, 15% have early stage localized disease, which has a 5-year survival rate of 91.9%.1 At time of diagnosis, 61% of patients have metastatic disease, which has a 5-year survival rate of 27.3%.1

CMYK Vers

Job Number: 20262 Revision No: 0

EDITORIAL BOARD EDITOR-IN-CHIEF

Beth Faiman,

Shannon Hazen, RN, BSN, OCN

PhD(c), MSN, APRNBC, AOCN

Novant Health Presbyterian Cancer Center Charlotte, NC

Catherine Bishop,

Patricia Irouer Hughes, RN, MSN,

Cleveland Clinic Taussig Cancer Institute Cleveland, OH

DNP, NP, AOCNP

Melinda Oberleitner, RN,

Karla Wilson,

College of Nursing and Allied Health Professions University of Louisiana Lafayette, LA

City of Hope National Medical Center Duarte, CA

Jayshree Shah, NP

Pharmacy John F. Aforismo,

DNS, APRN, CNS

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Johns Hopkins Kimmel Cancer Center/Sibley Infusion Washington, DC

BSN, OCN

Deena Damsky Dell, MSN, RN-BC,

Taline Khoukaz,

Gary Shelton,

University of Southern California Norris Cancer Center & Hospital Los Angeles, CA

NYU Clinical Cancer Center New York, NY

AOCN, LNC

Fox Chase Cancer Center Philadelphia, PA

Wendy DiSalvo,

DNP, APRN, AOCN Genentech New London, NH

Denice Economou,

RN, MN, CNS, AOCN City of Hope National Medical Center Duarte, CA

Constance Engelking, RN,

MS, CNS, OCN

The CHE Consulting Group, Inc. Mt. Kisco, NY

Amy Ford, RN,

BSN, OCN Biodesix, Inc. Dallas, TX

Piedmont Healthcare Rex, GA

NP, MSN, ACNP-C

MSN, NP, ANP-BC, AOCNP

Sandra E. Kurtin,

Lori Stover, RN,

Arizona Cancer Center Tucson, AZ

Western Pennsylvania Cancer Institute Pittsburgh, PA

Ann McNeill,

Joseph D. Tariman,

RN, MS, AOCN, ANP-C

MSN, RN, NP-C, OCN

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Kena C. Miller, RN, MSN, FNP

Roswell Park Cancer Institute Buffalo, NY

Patricia Molinelli, MS, RN, APN-C, AOCNS

Somerset Medical Center Somerville, NJ

BSN

PhD, APRN, BC

Northwestern University Myeloma Program Chicago, IL

Jacqueline Marie Toia, RN, MS, DNP

Northwestern University Myeloma Program Chicago, IL

Pamela Hallquist Viale, RN, MS,

CS, ANP, AOCN Saratoga, CA

RN, MSN, FNP-C, CPON

BSc Pharm, RPh, FASCP RJ Health Systems International, LLC Wethersfield, CT

Nutrition Karen Connelly, RD, CSO

Somerset Medical Center Somerville, NJ

Patient Advocacy Peg Ford

Ovarian Cancer Alliance San Diego, CA

Social Work Carolyn Messner, DSW, MSW, LCSW-R, BCD CancerCare New York, NY

Genetic Counseling Cristi Radford, MS, CGC

Ambry Genetics Sarasota, FL

Managed Care and Pharmaceutical Management Burt Zweigenhaft, BS

OncoMed Onco360 Great Neck, NY

Sharon S. Gentry,

Ellen A. Neylon,

RN, MSN, AOCN, CBCN

MSN, FNP-BC, CCRP, OCN

Novant Health Derric L. Davis Cancer Center Winston-Salem, NC

Columbia University Medical Center Center for Lymphoid Malignancies New York, NY

Cassandra J. Hammond, RN,

Dolores “Jeff” Nordquist, RN, MS,

Avid Education Partners, LLC Sharpsburg, MD

Mayo Clinic Rochester, MN

MSN, CRNP

www.TheOncologyNurse.com

CS, FNP

Connie Visovsky,

PhD, RN, ACNP-BC University of South Florida College of Nursing Tampa, FL

Rita Wickham,

PhD, RN, AOCN

Northern Michigan University Independent Oncology & Palliative Care Consultant Marquette, MI

Isabell Castellano, RN

Bristol-Myers Squibb Children’s Hospital Robert Wood Johnson University Hospital New Brunswick, NJ

Jeanne Westphal, RN

Meeker County Memorial Hospital Litchfield, MN

DECEMBER 2013 I VOL 6, NO 11

FROM THE EDITOR PUBLISHING STAFF Senior Vice President, Sales & Marketing Philip Pawelko ppawelko@the-lynx-group.com Group Director, Sales & Marketing John W. Hennessy jhennessy2@the-lynx-group.com Publisher Russell Hennessy rhennessy@the-lynx-group.com Editorial Director Kristin Siyahian ksiyahian@the-lynx-group.com Managing Editor Kristen Olafson kolafson@the-lynx-group.com Copy Editors Mollie Friedman Peggy Roeske Editorial Assistant Jennifer Brandt Production Manager Stephanie Laudien

THE LYNX GROUP

his month’s issue of The Oncology Nurse-APN/PA (TON) has a focus on ovarian cancer. We update you with some of the latest research as presented at the European Cancer Congress (ECCO/ESMO/ESTRO), the Chemotherapy Foundation Symposium, and the AACR-NCIEORTC International Conference on Molecular Targets and Cancer Beth Faiman, PhD(c), Therapeutics. MSN, APRN-BC, AOCN In addition, Peg Ford reflects on Editor-in-Chief “how things have changed not only in treatment, but also in research” since she became involved in the world of medicine as an advocate after her own battle with ovarian cancer. Peg states “Because ovarian cancer is very heterogeneous molecularly, the need for personalized precision treatment is advancing the interest and focus of the scientific world.” She tells us about some early-stage studies, including of the “PapGene” test, a 3-in-1 screening for gynecologic cancers. Be sure to see Peg’s list of resources for all involved in the

President/CEO Brian Tyburski

READER POLL

Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Director, Human Resources Blanche Marchitto Associate Director, Content Strategy & Development John Welz

Have you treated patients who are healthcare professionals?

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DECEMBER 2013 I VOL 6, NO 11

fight against ovarian cancer—from patients and survivors to researchers and healthcare providers. The Patient’s Voice column for this month was written by Tania Homonchuk. Tania is an emergency room doctor who is an ovarian cancer survivor. Her story from “the other side of the stethoscope” gives us a unique perspective on how a woman copes with receiving this diagnosis (“How do you tell your kids you have cancer?”) and subsequent treatments. Tania encourages us all to “think about nonspecific symptoms differently and keep ovarian cancer in mind—it is so silent and for many the journey to diagnosis is long and arduous.” Be sure to read Angela Long’s article, “A Thrust Into Vulnerability.” She notes that she has found it bewildering how differently patients and survivors perceive their cancer journeys. Angela discusses how “vulnerability” is the key that shapes one’s experience with cancer, a realization she came to after viewing a TED talk by Brené Brown. Brown believes that the ability to accept this vulnerability can lead individuals to “turn life’s challenges into gateways to courage, compassion, and connection.” Angela’s insight can help us all as we work with patients and survivors. All of us at TON wish you the best for 2014. l

o No

©iStockphoto.com/Slobodan Vasic

ania Homonchuk gives us a unique perspective— she is an emergency room doctor who was diagnosed with stage 3C ovarian cancer. She tells us that her “journey since diagnosis has been chock-full of experiences on the patient side of things.” Tania points out that “the nursing care was so important: first the focus on small steps

and then getting stronger to get on with the rest of the treatment.” Have you been involved with the treatment of other healthcare professionals who have received a cancer diagnosis? Please let us know about your experience in providing care for a patient who is used to being on “the other side of the stethoscope.”

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

The Oncology Nurse-APN/PA®, ISSN 1944-9798 (print); ISSN 1944-9801 (online) is published 11 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 ©2013 by Green Hill Healthcare Communications, LLC. All rights reserved. The Oncology Nurse-APN/PA® 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 Nurse-APN/PA®, 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 Nurse-APN/PA® 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 Nurse-APN/PA® 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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Now enrolling

Investigating ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia Phase II Open-Label Study of the Efficacy and Safety of ABT-199 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia Harboring the 17p Deletion N=100

ABT-199 is an investigational agent that has not been approved by regulatory agencies for the use under investigation in this trial. Primary Endpoint

Secondary Endpoints

• Overall response rate

• • • • • • • •

Complete remission rate Partial remission rate Duration of response Progression-free survival Time to progression Overall survival Percentage of patients who move on to stem-cell transplant Safety and tolerability of ABT-199

Key Inclusion Criteria • Adult patients ≥18 years of age • Diagnosis of CLL that meets 2008 IWCLL NCI-WG criteria (relapsed/refractory after receiving ≥1 prior line of therapy and 17p deletion) • ECOG performance score of ≤2 • Adequate bone marrow function • Adequate coagulation, renal, and hepatic function, per laboratory reference range

NCT#01889186 Reference: ClinicalTrials.gov.

To learn more about this study, please visit www.ClinicalTrials.gov.

OVARIAN CANCER Antiangiogenesis Pursued in High-Risk Ovarian Cancer Continued from cover Trials of Primary Therapy Studies of frontline therapy have shown that primary therapy with weekly paclitaxel appears to be more effective than other schedules. The value of incorporating antiangiogenesis into up-front regimens is based on exploratory analysis of phase 3 trials, he said. To date, the addition of an angiogenesis inhibitor, typically bevacizumab, to chemotherapy improves progression-free survival (PFS) but does not extend OS. Two trials of up-front treatment for high-grade serous ovarian cancer, ICON7 and GOG-0218, showed a modest difference in PFS and no difference in OS with the addition of the anti–vascular endothelial growth factor (VEGF) therapy bevacizumab compared with platinum-based chemotherapy. However, exploratory analysis suggests that patients with moderateto high-risk bulky disease have better outcomes with bevacizumab. A contrary finding in the AGOOVAR12 trial that compared che-

motherapy plus or minus nintedanib showed a slight PFS benefit, but in an exploratory analysis, the low-risk group did better with nintedanib. In addition, nintedanib inhibits VEGF receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor, and targets tumor cells directly; thus it may have a different effect than bevacizumab, Bookman said.

Weekly paclitaxel was identified as the preferred schedule for this drug, improving both PFS and OS. The next trial looked at weekly paclitaxel plus or minus bevacizumab. GOG-0262/ACRIN 6695 showed no difference in PFS with the addition of bevacizumab to chemotherapy. In an exploratory analysis, median PFS was 10.6 months in patients treated

In the primary surgery arm, 16% of patients underwent optimal debulking versus 40% in the neoadjuvant chemotherapy arm. Primary surgery was associated with more frequent toxicity, with 48% of patients experiencing grades 3 or higher toxicities versus 40% in the neoadjuvant chemotherapy arm. Grade 3 or 4 postoperative complications were reported in 24% of the primary surgery arm compared with 14% in the neoadjuvant chemotherapy arm. Neoadjuvant chemotherapy also led to shorter hospital stays: discharge within 14 days was possible in 74% of those in the primary surgery arm versus 92% in the neoadjuvant chemotherapy arm. Also, deaths within 28 days of treatment numbered 5 (5.6%) in the primary surgery arm compared with 1 (0.5%) in the neoadjuvant chemotherapy arm. The study also demonstrated noninferiority of neoadjuvant chemotherapy for survival outcomes: median PFS was 10.3 months for primary surgery versus 11.7 months for neoadjuvant chemotherapy, and OS was 22.8 months versus 24.5 months, respectively. In formal discussions of this trial, Jonathan S. Berek, MD, director of the Stanford Women’s Cancer Center, California, said that the patients enrolled in the MRC CHORUS trial had a worse prognosis and were a bit older, suggesting that patient selection is important when considering neoadjuvant chemotherapy versus surgery as primary treatment for advanced ovarian cancer. l

Trials in Advanced Recurrent Disease The OCEANS trial in platinum-sensitive disease showed that the addition of bevacizumab to chemotherapy improved PFS. The AURELIA study in platinum-resistant disease found that bevacizumab improved PFS. Both trials found no difference in OS favoring the addition of bevacizumab. “These studies suggest that bevacizumab is effective in improving PFS in both platinum-sensitive and platinum-resistant disease,” Bookman said. In a subset analysis of AURELIA, in which chemotherapy was selected by physician’s choice, the most striking benefits were observed when bevacizumab was added to weekly paclitaxel. No additional benefit was seen when bevacizumab was used with pegylated doxorubicin or topotecan, he noted. The ICON6 trial in recurrent disease found that when added to chemotherapy, cediranib—a potent inhibitor of VEGF tyrosine kinase—improved OS: median OS was 20.3 months without cediranib versus 26 months when this agent was added. The TRINOVA-1 trial evaluated the addition of trebananib to chemotherapy. Trebananib is an investigational antiangiogenesis recombinant peptide that inhibits the binding of angiopoietin 1 and 2 to the Tie2 receptor—a different target than that of bevacizumab. In that study, PFS was extended with trebananib. Survival results are not yet available. Trebananib has a different toxicity profile that includes edema, pleural effusion, ascites, and weight increase. Bookman suggested that these treatment-emergent adverse events may predict clinical response to this novel agent. The GOG-3001 trial is evaluating carboplatin/paclitaxel plus or minus trebananib, and the trial is beginning accrual. Remaining issues include the best target for antiangiogenesis—VEGF receptors, angiopoietin 1 and 2? “The cellular target of angiogenesis is not obvious,” Bookman continued. “It is not clear which is better—to target the vascular endothelium or directly target the tumor.” l

Reference

“The cellular target of angiogenesis is not obvious. It is not clear which is better—to target the vascular endothelium or directly target the tumor.” Michael Bookman, MD

The AGO-OVAR16 trial showed that maintenance therapy with pazopanib (a tyrosine kinase inhibitor) improved PFS but had no effect on survival.

with weekly paclitaxel minus bevacizumab and 14.2 months with the addition of bevacizumab. Thus, weekly paclitaxel and bevaciz-

Neoadjuvant Chemotherapy a Reasonable Option for Advanced Ovarian Cancer Alice Goodman

eoadjuvant chemotherapy was found equivalent to primary surgery followed by chemotherapy for patients with advanced ovarian cancer in the Medical Research Council Chemotherapy Or Upfront Surgery (MRC CHORUS) trial reported at the 2013 American Society of Clinical Oncology Annual Meeting. In this study, more patients who received neoadjuvant chemotherapy were able to undergo optimal debulking surgery and fewer had postoperative complications and deaths, but rates of progression-free survival (PFS) and overall survival (OS) were similar in both arms. Lead author Sean Kehoe, MD, John Radcliffe Hospital, Oxford, United Kingdom, said that because these patients were, in general, older and sicker than in some other recent trials, neoadjuvant chemotherapy was a good option in this subpopulation. MRC CHORUS joins the EORTC 55971 trial as the second randomized trial to show noninferiority of neoadjuvant chemotherapy compared with primary surgery in advanced ovarian cancer, he noted. From March 2004 to August 2010, 552 patients with stage III-IV ovarian cancer were enrolled in the MRC CHORUS trial. As 2 patients were randomized in error, the study population ultimately included 550 patients. Patients were randomized 1:1 to primary debulking surgery followed by 6 cycles of platinum-based chemotherapy (n=276) versus 3 cycles of neoadjuvant platinum-based chemotherapy followed by surgery and 3 cycles of chemotherapy (n=199). Treatment arms had comparable baseline characteristics: median age was 65.5 years; 20% were WHO Performance Status 2-3; median tumor size was 8 cm; and 25% were stage IV. About 79% of those in the primary surgery arm and 68% of those in the neoadjuvant chemotherapy arm had highgrade serous carcinoma, which is particularly lethal.

DECEMBER 2013 I VOL 6, NO 11

umab had the best results. A biomarker substudy of GOG-0262 suggested that weekly paclitaxel by itself has antiangiogenic effects on tumor blood flow and tumor volume, Bookman noted.

Kehoe S, Hook J, Nankivell M, et al. Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: results from the MRC CHORUS trial. J Clin Oncol. 2013;31(suppl):Abstract 5500. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

Bookman M. Perspective on antiangiogenic trials in ovarian cancer. Presented at: 2013 Chemotherapy Foundation Symposium; November 7, 2013; New York, NY.

www.TheOncologyNurse.com

NEWS BRIEFS Continued from cover

The Developing Role of PARP Inhibition Poly (ADP ribose) polymerase (PARP) inhibitors show excellent activity in ovarian cancer. The optimal role of PARP inhibitors in ovarian cancer is not yet determined. Currently, 5 PARP inhibitors are in various stages of development, and the most widely studied is olaparib. PARP inhibitors cause multiple double-strand breaks in DNA. In tumor cells that harbor BRCA1 and BRCA2 mutations, these breaks cannot be repaired, leading to cell death. “The simple version is that PARP is important. PARP inhibitors lock the PARP enzyme on DNA and prevent normal DNA repair. These are DNAdamaging agents, and some subsets of patients may be more susceptible to PARP inhibition,” explained Elise C. Kohn, MD, National Institutes of Health, Bethesda, Maryland. She updated attendees on PARP inhibition in ovarian cancer at the 2013 Chemotherapy Foundation Symposium.1 The 5 PARP inhibitors under development include olaparib, rucaparib, niraparib, veliparib, and BMN-673. The first 3 are in registration studies, and the latter 2 are in phase 1/2 studies. “I have confidence that this new class of agents is exciting in ovarian cancer. Encourage patient participation in clinical trials,” she told listeners. Studies suggest that olaparib is more active in patients with germline BRCA mutations than in those without them, and platinum-sensitive patients seem to be the most responsive. Olaparib improved progression-free survival (PFS) as maintenance therapy in patients with platinum-sensitive ovarian cancer in a randomized controlled trial. In an updated analysis, olaparib improved PFS by 65% overall; a more robust effect on PFS was observed in patients with germline BRCA1 and BRCA2 mutations, with an 82% improvement in PFS. However, olaparib maintenance was also effective in those with BRCA wild-type mutations, improving PFS by 47%.2 The phase 2 AZ Study 41 showed a PFS benefit for olaparib/carboplatin/paclitaxel followed by olaparib maintenance versus carboplatin/paclitaxel followed by no further treatment; median PFS was 12.2 months with olaparib versus 9.6 months without.3 “These results were provocative,” Kohn said. “PARP inhibitors are still being investigated in a wide variety of ovarian cancer patients with and without mutations and in combination with other drugs,” she continued. A phase 1 trial of olaparib plus cediranib (VEGFR inhibitor) showed clinical benefit in ovarian cancer, and a randomized phase 2 study of this combination has been initiated. Biomarkers are needed to determine

www.TheOncologyNurse.com

which patients will respond to PARP inhibition. Germline BRCA1 and BRCA2 mutations are predictive of response and duration of response, but other biomarkers are needed for patients without these mutations. It may be that a homologous recombinant defect (HRD) is a biomarker, but more studies are needed. “The HRD score is a provocative direction to study,” Kohn stated.

The optimal role of PARP inhibition remains to be determined; potential opportunities include prevention, after diagnosis, at first remission, concurrent with maintenance therapy, in platinum-sensitive recurrent ovarian cancer with chemotherapy, and in platinum-refractory patients. “We don’t know the answer,” Kohn told listeners. l

References

1. Kohn E. PARP inhibitors in ovarian cancer. Presented at: 2013 Chemotherapy Foundation Symposium; November 7, 2013; New York, NY. 2. Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382-1392. 3. Oza AM, Cibula D, Oaknin A, et al. Olaparib plus paclitaxel plus carboplatin (P/C) followed by olaparib maintenance treatment in patients (pts) with platinum-sensitive recurrent serous ovarian cancer (PSR SOC): a randomized, open-label phase II study. J Clin Oncol. 2012;30(15 suppl):Abstract 5001.

Continued on page 10

IS NOW

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MAY 2013 • VOLUME 6 • NUMBER 2

CONSIDERATIONS in

Multiple Myeloma

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ASK THE EXPERTS: Maintenance Settings PUBLISHING STAFF Group Director, Sales & Marketing John W. Hennessy john@greenhillhc.com Editorial Director Susan A. Berry susan@coexm.com Senior Copy Editor BJ Hansen Copy Editors Dana Delibovi Rosemary Hansen Grants/Project Associate Susan Yeager The Lynx Group President/CEO Brian Tyburski Chief Operating Officer Pam Rattanonont Ferris Vice President of Finance Andrea Kelly Director of Human Resources Blanche Marchitto Associate Editorial Director, Projects Division Terri Moore

LETTER

FROM THE

EDITOR-IN-CHIEF

Over the past decade, significant progress has been made in the management of multiple myeloma, including new standards of care and the development and approval of several novel, effective agents. Despite this progress, more work needs to be done and numerous questions remain regarding the application and interpretation of recent clinical advances. In this sixth annual “Considerations in Multiple Myeloma” newsletter series, we continue to explore unresolved issues related to the management of the disease and new directions in treatment. To ensure an interprofessional perspective, our faculty is comprised of physicians, nurses, and pharmacists from leading cancer institutions, who provide their insight, knowledge, and clinical experience related to the topic at hand. In this second issue, experts from Dana-Farber Cancer Institute answer questions related to the management of patients in the maintenance setting.

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The Elodia Kehm Chair of Hematology Professor of Medicine Director, Lymphoma Program Rush University Medical Center/Rush University Chicago, IL

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NEWS BRIEFS Continued from page 9

Bevacizumab Appears to Benefit High-Risk Patients Two phase 3 trials presented at the 2013 European Cancer Congress suggest that the optimal role of bevacizumab will be in high-risk patients. AURELIA is the first phase 3 study to evaluate the addition of bevacizumab to chemotherapy in platinum-resistant ovarian cancer (defined as progression within 6 months of last platinum-containing therapy).1 The addition of bevacizumab to chemotherapy significantly improved progression-free survival (PFS) from 3.4 months to 6.7 months (P <.001), and median overall survival (OS) was improved from 13.3 months with chemotherapy alone to 16.6 months, but this did not reach statistical significance. Chemotherapy agents included paclitaxel, topotecan, and liposomal doxorubicin. “No single agent has shown superiority to weekly paclitaxel, topotecan, or liposomal doxorubicin. Median survival in platinum-resistant ovarian cancer is typically around 12 months,” said lead author

Petronella Witteveen, MD, DCOG, of University Medical Centre Utrecht, in the Netherlands. AURELIA randomized 361 patients to receive bevacizumab plus investigator’s choice of chemotherapy versus chemotherapy alone. Treatment was continued until disease progression, unacceptable toxicity, or consent withdrawal.

The difference in survival for high-risk patients given bevacizumab was clinically meaningful. At progression, patients in the chemotherapy arm were allowed to cross over to bevacizumab monotherapy; bevacizumab was discontinued after progression in the bevacizumab plus chemotherapy arm.

An exploratory subgroup analysis of OS suggested that weekly paclitaxel was the best partner for bevacizumab. In the weekly paclitaxel cohort, median OS was 22.4 months for bevacizumab versus 13.2 months in controls, representing a 35% relative improvement favoring bevacizumab. By contrast, in the cohort treated with liposomal doxorubicin, median OS was 13.7 months in those randomized to receive bevacizumab plus chemotherapy versus 14.1 months with chemotherapy only. For the topotecan-treated cohort, median PFS was 13.8 months for those treated with bevacizumab plus chemotherapy versus 13.3 months for chemotherapy only. “The effect of weekly paclitaxel should be considered exploratory and requires prospective validation,” Witteveen said. No new safety concerns were identified in an updated safety analysis. The main grade ≥3 toxicities in the bevacizumab arm were hypertension (7.8%) and proteinuria (2.2%).

Trebananib in Platinum-Sensitive Ovarian Cancer A new antiangiogenesis inhibitor with a different mechanism of action than bevacizumab shows promise in platinum-sensitive ovarian cancer, according to results of the phase 3 TRINOVA-1 trial presented at the 2013 meeting of the European Cancer Congress. Trebananib added to paclitaxel prolonged the time to disease progression or death by 52% compared with paclitaxel plus placebo (P <.001), said Bradley Monk, MD, Creighton University School of Medicine and University of Arizona Cancer Center, Phoenix. Although angiogenesis is a proven target in ovarian cancer, anti–vascular endothelial growth factor (VEGF) therapy (with bevacizumab) causes adverse effects. Trebananib is a different approach, targeting a non-VEGF angiogenesis factor—angiopoietin 1 and angiopoietin 2. The hope is that this approach will be effective and have fewer adverse effects than a VEGF-targeted strategy, Monk said. TRINOVA-1 enrolled 919 women with recurrent epithelial ovarian cancer and randomized them to receive treatment with weekly intravenous (IV) trebananib 15 mg/kg plus weekly IV paclitaxel (3 weeks on, 1 week off) or with placebo plus weekly paclitaxel (3 weeks on, 1 week off). Patients were treated until disease progression, toxicity, or withdrawal of consent. Patients were stratified according to progression-free interval, measurable disease, and geographic region. At baseline, patients had received up to 3 prior cytotoxic regimens and had a progression-free interval of <12 months. One prior regimen failed in 40% of patients, 2 prior therapies in 40%, and 3 prior therapies in 20%. Monk presented primary progression-free survival (PFS) and interim overall survival (OS) results of this international trial. At a median follow-up of 10 months, median PFS was 7.2 months in the trebananib group and 5.4 months for placebo (hazard ratio, 0.66; 95% confidence interval, 0.56-0.76; P <.001). A prespecified subgroup analysis found that trebananib improved PFS in all subgroups. Overall response rate was

DECEMBER 2013 I VOL 6, NO 11

38% with trebananib versus 30% with placebo (most were partial responses). Trebananib did not appear to increase toxicity when added to paclitaxel, according to the safety analysis. The rate of adverse events of any grade was similar between the 2 treatment arms: 96% for trebananib and 97% for placebo. The major toxicity of trebananib was edema: 57% versus 26% (any grade) for those in the placebo arm. Very few grade ≥3 adverse events were reported with trebananib. No increase in VEGF-associated adverse effects was seen with trebananib (ie, hypertension, proteinuria, wound healing complications, arterial thrombotic events). Neutropenia and anemia were more common in the placebo arm, and neurotoxicity was more common in the trebananib arm, which may be attributable to increased exposure to paclitaxel in that arm. An interim OS analysis showed a difference of approximately 2 months favoring trebananib (19 months vs 17.3 months for the placebo arm), but this is only a preliminary analysis, Monk reminded listeners. TRINOVA-1 incorporated patient-reported outcomes using 3 different quality-of-life questionnaires: Functional Assessment of Cancer Therapy-Ovarian (FACT-O), Ovarian Cancer Screening (OCS), and EuroQol 5-dimension (EQ5D). On these measures, no quality-of-life differences were reported between the 2 treatment arms. Trebananib is continuing to be developed for ovarian cancer. The formal discussant of this trial, Antonio Casado, MD, Hospital Universitario San Carlos, Madrid, Spain, said, “Weekly paclitaxel and trebananib could be an option in patients who progress within 12 months after 1 to 3 previous lines of therapy.” l Reference

Monk BJ, Poveda A, Vergote I, et al. A phase III, randomized, double-blind trial of weekly paclitaxel plus the angiopoietin 1 and 2 inhibitor, trebananib, or placebo in women with recurrent ovarian cancer: TRINOVA-1. Presented at: 2013 European Cancer Congress; September 27-October 1, 2013; Amsterdam, the Netherlands. Abstract LBA41.

The ICON7 trial evaluated bevacizumab in women with newly diagnosed ovarian cancer. The primary analysis (previously reported) showed a median PFS of 17.3 months for chemotherapy alone versus 19 months for bevacizumab added to chemotherapy (P = .004).2 In the final survival analysis presented at the European Cancer Congress, median OS was 58 months in the study for both arms; however, poor-prognosis patients experienced a 4.8-month prolongation of survival (from 34.5 months to 39.3 months) if they received bevacizumab.3 “The survival benefit in the overall trial of 0.9 months is not clinically meaningful. However in the high-risk subgroup, bevacizumab did show a clinically meaningful benefit of 4.8 months,” said Amit Oza, MD, Princess Margaret Cancer Centre, University of Toronto, Canada. The international study randomized 1528 women to 6 cycles of every-3-week carboplatin/paclitaxel versus carboplatin/ paclitaxel plus bevacizumab for 5 or 6 cycles followed by bevacizumab for 12 additional every-3-week cycles until disease progression. Patients were prestratified according to stage, extent of debulking, and time of therapy. A third of the women were considered high risk (stage III with >1 cm residual disease, stage IV, and nondebulked). At a median follow-up of 49 months, PFS was not significantly different between the 2 arms, similar to the first interim analysis presented previously. Over 4 years, the difference between the 2 curves was gradually eroded, Oza said. Because the curves are nonproportional, the final OS analysis was conducted using a restricted means analysis, and the difference between the 2 arms was 0.9 months, which was not statistically or clinically meaningful. In a predefined high-risk subgroup of patients, the curves for the 2 arms separated and the bevacizumab arm was superior throughout the study, with a 4.8-month improvement over the control arm. Oza said the difference in survival for high-risk patients given bevacizumab was clinically meaningful. l References

1. Witteveen P, Lortholary A, Fehm T, et al. Final overall survival (OS) results from AURELIA, an open-label randomized phase III trial of chemotherapy (CT) with or without bevacizumab (BEV) for platinum-resistant ovarian cancer. Presented at: 2013 European Cancer Congress; September 27-October 1, 2013; Amsterdam, the Netherlands. Abstract LBA5. 2. Perren TJ, Swart AM, Pfisterer J, et al; the ICON7 investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484-2496. 3. Oza AM, Perren TJ, Swart AM, et al. ICON7: final overall survival results in the GCIG phase III randomized trial bevacizumab in women with newly diagnosed ovarian cancer. Presented at: 2013 European Cancer Congress; September 27-October 1, 2013; Amsterdam, the Netherlands. Abstract LBA6.

www.TheOncologyNurse.com

NEWS BRIEFS BMN-673: Investigational PARP Inhibitor events occurring in <30% of patients were myelosuppression, fatigue, nausea, and alopecia. BioMarin Pharmaceuticals has mount-

Reference

Wainberg ZA, de Bono JS, Mina L, et al. Update on firstin-man trial of novel oral PARP inhibitor BMN 673 in patients with solid tumor. Presented at: Molecular Targets and Cancer Therapeutics; October 22, 2013; Boston, MA. Abstract C295.

S:7.25”

NOW RECRUITING

Investigators Study of the long-term safety and efficacy of darbepoetin alfa in anemic patients with Non-Small Cell Lung Cancer (NSCLC) receiving chemotherapy Phase 3 study with approximately 3,000 subjects at 500 study sites globally KEY ELIGIBILITY CRITERIA*

PRIMARY ENDPOINT

• Stage IV NSCLC

• Overall survival

• Receiving 1st-line myelosuppressive

SECONDARY ENDPOINTS

chemotherapy

• Progression-free survival

• Hemoglobin (Hb) ≤ 11 g/dL

• Incidence of ≥ 1 red blood cell (RBC) transfusion or Hb ≤ 8.0 g/dL

• ECOG score ≤ 1

Darbepoetin alfa 500-mcg Q3W

2:1 Randomization (darbepoetin alfa:placebo)

End of Investigational Product

End of Treatment Period

Long-term Follow-up

Placebo Q3W

Week 0

Week 1

Disease progression or end of chemotherapy treatment

*Complete inclusion/exclusion criteria and additional study details can be found in the protocol. ECOG = Eastern Cooperative Oncology Group; Q3W = once every 3 weeks.

Cory Docken/Getty Images

For more information, please email Study-20070782@amgen.com or call 1-866-965-0782. Products under investigational study have not been approved by the FDA for the use under investigation in this trial.

AOCO3X0071_Recruitment782_AdAsize_r3.indd 1

www.TheOncologyNurse.com

ed a phase 3 study of BMN-673 versus physician’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine in metastatic breast cancer. l

S:9.75”

The investigational poly (ADP ribose) polymerase (PARP) inhibitor BMN673 achieved an objective response rate (ORR) of >40% and delayed disease progression by >6 months in patients with heavily pretreated advanced BRCA-related breast and ovarian cancers in a phase 1 trial. The first-in-human study was reported at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held in Boston, Massachusetts, in October 2013. Lead author Zev A. Wainberg, MD, Jonsson Comprehensive Cancer Center at the University of California Los Angeles, called the novel agent “the most potent PARP inhibitor in clinical development.” He said the drug had optimized pharmaceutical properties and can be given orally with a long half-life that allows once-daily dosing. “BMN-673 has high single-agent antitumor activity in ovarian and breast cancer patients with deleterious germline mutations of BRCA1 and BRCA2. The duration of response and progression-free survival appear to be promising in this early-phase trial,” Wainberg commented at a press conference. The study enrolled 87 patients with a variety of cancers: breast, ovarian, small cell lung cancer, and Ewing sarcoma. All patients had received a mean of 3 prior regimens (range, 1-13). Phase 1 response data were reported for 18 patients with germline BRCAmutated breast cancer, 28 patients with germline BRCA-mutated ovarian cancer, 24 patients with Ewing sarcoma, and 12 patients with small cell lung cancer. In 26 evaluable patients with BRCAmutated ovarian cancer, ORR was 46% and clinical benefit rate (including response rate and stable disease) was 82%. Median duration of response was 26.9 weeks, and median progression-free survival was 33.4 weeks. Among 18 patients with BRCAmutated breast cancer, 44% responded including 1 complete response. The rate of clinical benefit was 72%, with stable disease for at least 24 weeks. When patients received the recommended clinical dose of 1 mg/day for phase 2, ORR went up to 50% and the clinical benefit went up to 86%. Among patients with ovarian cancer, 70% had significant reductions in CA-125, several had no change, and 1 patient had an increase in CA-125. Responses were also seen in the small cell lung cancer cohort, where no BRCA mutations were observed. No responses were seen in patients with Ewing sarcoma. BMN-673 was tolerable in general. The most common drug-related adverse

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DECEMBER 2013 I VOL 6, NO 11

EMPOWERING PATIENTS AND SURVIVORS

A Thrust Into Vulnerability

T:17

Angela Long

“You can’t get to courage without walking through vulnerability.” –Brené Brown

s a cancer survivor and advocate, it has bewildered me how differently cancer patients and survivors perceive their cancer journeys. This variation in outlook ranges from being stuck in a state of fear, anger, shame, or blame, to viewing cancer as a “gift.” While watching Dr Brené Brown’s TED talk on vulnerability, which can be defined as “uncertainty, risk, and emotional exposure,” I realized that this is a key element in what shapes one’s cancer experience. Brown refers to her “breakdown/ spiritual awakening” and the year she spent in therapy coming to grips with her own vulnerability, a process she sought in her effort to research the factors that determine who suffers and who thrives through life’s ups and downs. Unlike Brown, cancer patients are not seeking opportunities to face their vulnerability. Much like Alice’s fall down the rabbit hole, hearing the words “you have cancer” thrusts us quite suddenly into a world of inescapable vulnerability. In an instant, our health, mortality, self-identity, independence, and relationships are all in question. An overwhelming sense of vulnerability haunts us through, and often after, the cancer journey. Despite the shock, pain, and fear that come with a cancer diagnosis, there are those who not only bounce back, but feel their lives have been improved by their cancer experience. According to Brown, these wholehearted individuals have the ability to cultivate courage, compassion, and connection in their daily lives and hence experience positive growth from even the most negative situations. Brown finds that a common thread among the wholehearted is their ability to embrace vulnerability and own their story. We are conditioned to believe that vulnerability is a sign of weakness and thus avoid situations that remind us of our own. Once diagnosed with cancer, we experience a level of vulnerability few of us ever imagined. Time and support from others enable some of us to process, accept, and adapt to the multitude of changes thrust upon us by a cancer diagnosis, while others never quite accept nor adjust to life

DECEMBER 2013 I VOL 6, NO 11

n tio a dic n I L TC P ne -Li d 2n

ISTODAX® (romidepsin) for injection is indicated for treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy. This indication is based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.

RECHARGE THE POSSIBILITIES

• Efficacy and safety evaluated in the largest prospective single-arm PTCL study (Study 3, N=131)1 • Studied in a pretreated, histologically diverse PTCL population1 • Patients could be treated until disease progression at their discretion and that of the investigator1

Important Safety Information WARNINGS AND PRECAUTIONS • Treatment with ISTODAX® (romidepsin) has been associated with thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, monitor these hematological parameters during treatment with ISTODAX and modify the dose as necessary • Serious and sometimes fatal infections have been reported during treatment and within 30 days after treatment with ISTODAX. The risk of life threatening infections may be higher in patients with a history of extensive or intensive chemotherapy • Electrocardiographic (ECG) changes have been observed with ISTODAX • In patients with congenital long QT syndrome, patients with a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as monitoring electrolytes and ECGs at baseline and periodically during treatment • Ensure that potassium and magnesium are within the normal range before administration of ISTODAX • Tumor lysis syndrome has been reported during treatment with ISTODAX. Patients with advanced stage disease and/or high tumor burden should be closely monitored and appropriate precautions taken, and treatment should be instituted as appropriate • ISTODAX may cause fetal harm when administered to a pregnant woman. Advise women to avoid pregnancy while receiving ISTODAX. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus (Pregnancy Category D)

ADVERSE REACTIONS Peripheral T-Cell Lymphoma The most common Grade 3/4 adverse reactions (>5%) regardless of causality in Study 3 (N=131) were thrombocytopenia (24%), neutropenia (20%), anemia (11%), asthenia/fatigue (8%), and leukopenia (6%), and in Study 4 (N=47) were neutropenia (47%), leukopenia (45%), thrombocytopenia (36%), anemia (28%), asthenia/fatigue (19%), pyrexia (17%), vomiting (9%), and nausea (6%).

S:7” T:8.125”

www.istodax.com

www.TheOncologyNurse.com

7.5”

EMPOWERING PATIENTS AND SURVIVORS with and after cancer. Brown counsels that it is those who can accept and even embrace their vulnerability who turn life’s challenges into gateways to courage, compassion, and connection.

Courage: While we may view vulnerability in ourselves as weakness, we often perceive it as courage in others. It takes courage to show our imperfections, let go of who we

think we should be, and accept who we are. Norma, a metastatic cancer survivor, said, “I found that with 6 broken vertebrae in my back, I couldn’t do many things I used to, which made

me (independent me) have to ask for help. My condition made me have to request special considerations, better chairs, cushions, closer parking, etc. Continued on page 14

Demonstrated efficacy in PTCL after at least 1 prior therapy in Study 3a1

15% ~60% 25%

(19/130) Complete Response Rate (CR+CRu) by independent central review (95% CI: 9.0, 21.9) • Similar complete response rates in the 3 major PTCL subtypes (NOS, AITL, ALCL)

9.2 months

(11/19) of Complete Responses (CR+CRu) exceeded • Follow-up was discontinued in the remaining 8 patients prior to 9.2 months (33/130) Objective Response Rate (CR+CRu+PR) by independent central review (95% CI: 18.2, 33.8)

1.8 months a

(~2 cycles) median time to Objective Response

Efficacy based on 130 patients with histological confirmation by independent central review.1

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Infections were the most common type of serious adverse event reported in Study 3 (N=131) and Study 4 (N=47). In Study 3, 25 patients (19%) experienced a serious infection, including 6 patients (5%) with serious treatment-related infections. In Study 4, 11 patients (23%) experienced a serious infection, including 8 patients (17%) with serious treatment-related infections. The most common adverse reactions regardless of causality in Study 3 (N=131) were nausea (59%), asthenia/fatigue (55%), thrombocytopenia (41%), vomiting (39%), diarrhea (36%), and pyrexia (35%), and in Study 4 (N=47) were asthenia/fatigue (77%), nausea (75%), thrombocytopenia (72%), neutropenia (66%), anemia (62%), leukopenia (55%), pyrexia (47%), anorexia (45%), vomiting (40%), constipation (40%), and diarrhea (36%).

DRUG INTERACTIONS • Monitor prothrombin time and International Normalized Ratio in patients concurrently administered ISTODAX (romidepsin) and warfarin sodium derivatives • Romidepsin is metabolized by CYP3A4 Monitor patients for toxicity related to increased romidepsin exposure and follow dose modifications for toxicity when ISTODAX is initially co-administered with strong CYP3A4 inhibitors Avoid co-administration of ISTODAX with rifampin and other potent inducers of CYP3A4 • Exercise caution with concomitant use of ISTODAX and P-glycoprotein (P-gp, ABCB1) inhibitors

USE IN SPECIFIC POPULATIONS • Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother • Patients with moderate and severe hepatic impairment and/or patients with end-stage renal disease should be treated with caution Please see Brief Summary of Full Prescribing Information, including WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS, on the following pages. Reference: 1. ISTODAX [package insert]. Summit, NJ: Celgene Corp; 2013.

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A Thrust Into Vulnerability Continued from page 13 I hated drawing attention to myself that way, but it was unavoidable. This to me was courage, courage to accept that things had changed, that my old carefree and healthy existence was gone, and that I could either give up or pull up my big-girl panties and move forward. I chose the latter.”

Compassion: In our search for compassion, we need someone who embraces us for both our strengths and our struggles. Compassion is a relationship between equals. We draw from our own experiences of struggle and fear so that we can be present and empathize with the strug-

gles and fears of others. One’s cancer experience can be a vast resource to draw from when offering support to others. In knowing our own suffering, we often develop the desire to alleviate the suffering of others. Compassion leads us not only to help others, but also to accept help T:7”

from others. After my diagnosis, I found it difficult to request and accept help from others. Brown suggests that when we find it difficult to accept or ask for help without self-judgment, we are likely to subconsciously judge those who need our help. “Until we can receive with an open heart, we are

Only

monitored, appropriate precautions should be taken, and treatment should be instituted as appropriate.

ISTODAX® (romidepsin) for injection For intravenous infusion only The following is a Brief Summary of the Prescribing Information for the peripheral T-cell lymphoma indication only; see Full Prescribing Information for complete product information.

5.5 Use in Pregnancy There are no adequate and well-controlled studies of ISTODAX in pregnant women. However, based on its mechanism of action and findings in animals, ISTODAX may cause fetal harm when administered to a pregnant woman. In an animal reproductive study, romidepsin was embryocidal and resulted in adverse effects on the developing fetus at exposures below those in patients at the recommended dose of 14 mg/m2/week. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus [See Use in Specific Populations (8.1)]. 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Peripheral T-Cell Lymphoma The safety of ISTODAX was evaluated in 178 patients with PTCL in a sponsor-conducted pivotal study (Study 3) and a secondary NCI-sponsored study (Study 4) in which patients received a starting dose of 14 mg/m2. The mean duration of treatment and number of cycles in these studies were 5.6 months and 6 cycles. Common Adverse Reactions Table 2 summarizes the most frequent adverse reactions (≥10%) regardless of causality, using the NCI-CTCAE, Version 3.0. The AE data are presented separately for Study 3 and Study 4. Laboratory abnormalities commonly reported (≥10%) as adverse reactions are included in Table 2. Table 2. Adverse Reactions Occurring in ≥10% of Patients with PTCL in Study 3 and Corresponding Incidence in Study 4 (N=178) Study 3 Study 4 (N=131) (N=47) Grade 3 Grade 3 Adverse Reactions n (%) All or 4 All or 4 Any adverse reactions 127 (97) 86 (66) 47 (100) 40 (85) Gastrointestinal disorders Nausea 77 (59) 3 (2) 35 (75) 3 (6) Vomiting 51 (39) 6 (5) 19 (40) 4 (9) Diarrhea 47 (36) 3 (2) 17 (36) 1 (2) Constipation 39 (30) 1 (<1) 19 (40) 1 (2) Abdominal pain 18 (14) 3 (2) 6 (13) 1 (2) Stomatitis 13 (10) 0 3 (6) 0 General disorders and administration site conditions Asthenia/Fatigue 72 (55) 11 (8) 36 (77) 9 (19) Pyrexia 46 (35) 7 (5) 22 (47) 8 (17) Chills 14 (11) 1 (<1) 8 (17) 0 Edema peripheral 13 (10) 1 (<1) 3 (6) 0 Blood and lymphatic system disorders Thrombocytopenia 53 (41) 32 (24) 34 (72) 17 (36) Neutropenia 39 (30) 26 (20) 31 (66) 22 (47) Anemia 32 (24) 14 (11) 29 (62) 13 (28) Leukopenia 16 (12) 8 (6) 26 (55) 21 (45) Metabolism and nutrition disorders Anorexia 37 (28) 2 (2) 21 (45) 1 (2) Hypokalemia 14 (11) 3 (2) 8 (17) 1 (2) Nervous system disorders Dysgeusia 27 (21) 0 13 (28) 0 Headache 19 (15) 0 16 (34) 1 (2) Respiratory, thoracic and mediastinal disorders Cough 23 (18) 0 10 (21) 0 Dyspnea 17 (13) 3 (2) 10 (21) 2 (4) Investigations Weight decreased 13 (10) 0 7 (15) 0 Cardiac disorders Tachycardia 13 (10) 0 0 0

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1 INDICATIONS AND USAGE ISTODAX is indicated for: • Treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy. This indication is based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated. 2 DOSAGE AND ADMINISTRATION 2.1 Dosing Information The recommended dose of romidepsin is 14 mg/m2 administered intravenously over a 4-hour period on days 1, 8, and 15 of a 28-day cycle. Cycles should be repeated every 28 days provided that the patient continues to benefit from and tolerates the drug. 2.2 Dose Modification Nonhematologic toxicities except alopecia • Grade 2 or 3 toxicity: Treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline, then therapy may be restarted at 14 mg/m2. If Grade 3 toxicity recurs, treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline and the dose should be permanently reduced to 10 mg/m2. • Grade 4 toxicity: Treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline, then the dose should be permanently reduced to 10 mg/m2. • Romidepsin should be discontinued if Grade 3 or 4 toxicities recur after dose reduction. Hematologic toxicities • Grade 3 or 4 neutropenia or thrombocytopenia: Treatment with romidepsin should be delayed until the specific cytopenia returns to ANC ≥1.5×109/L and/or platelet count ≥75×109/L or baseline, then therapy may be restarted at 14 mg/m2. • Grade 4 febrile (≥38.5° C) neutropenia or thrombocytopenia that requires platelet transfusion: Treatment with romidepsin should be delayed until the specific cytopenia returns to ≤Grade 1 or baseline, and then the dose should be permanently reduced to 10 mg/m2. 2.3 Instructions for Preparation and Intravenous Administration ISTODAX should be handled in a manner consistent with recommended safe procedures for handling cytotoxic drugs. 5 WARNINGS AND PRECAUTIONS 5.1 Hematologic Treatment with ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, these hematological parameters should be monitored during treatment with ISTODAX, and the dose should be modified, as necessary [See Dosage and Administration (2.2) and Adverse Reactions (6)]. 5.2 Infection Serious and sometimes fatal infections, including pneumonia and sepsis, have been reported in clinical trials with ISTODAX. These can occur during treatment and within 30 days after treatment, and the risk of life threatening infections may be higher in patients with a history of extensive or intensive chemotherapy [See Adverse Reactions (6)]. 5.3 Electrocardiographic Changes Several treatment-emergent morphological changes in ECGs (including T-wave and ST-segment changes) have been reported in clinical studies. The clinical significance of these changes is unknown [See Adverse Reactions (6)]. In patients with congenital long QT syndrome, patients with a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. Potassium and magnesium should be within the normal range before administration of ISTODAX [See Adverse Reactions (6)]. 5.4 Tumor Lysis Syndrome Tumor lysis syndrome (TLS) has been reported to occur in 1% of patients with tumor stage CTCL and 2% of patients with Stage III/IV PTCL. Patients with advanced stage disease and/or high tumor burden should be closely

EMPOWERING PATIENTS AND SURVIVORS never really giving with an open heart. When we attach judgment to receiving help, we knowingly or unknowingly attach judgment to giving help.” In learning compassion, we open ourselves to truly reciprocal relationships and deeper human connections. Connection: Support is important during a cancer journey, but connection is often intrinsic to one’s emo-

Even within the cancer community, survivors can have a difficult time finding connection.

tional healing. Nothing creates a sense of connection for cancer patients like the words “me too.” It was not until

I was able to connect with someone who had “walked in my shoes” that I really felt understood. This connec-

T:7”

Serious Adverse Reactions Infections were the most common type of SAE reported. In Study 3, 25 patients (19%) experienced a serious infection, including 6 patients (5%) with serious treatment-related infections. In Study 4, 11 patients (23%) experienced a serious infection, including 8 patients (17%) with serious treatment-related infections. Serious adverse reactions reported in ≥2% of patients in Study 3 were pyrexia (7%), pneumonia, sepsis, vomiting (5%), cellulitis, deep vein thrombosis, (4%), febrile neutropenia, abdominal pain (3%), chest pain, neutropenia, pulmonary embolism, dyspnea, and dehydration (2%). In Study 4, serious adverse reactions in ≥2 patients were pyrexia (17%), aspartate aminotransferase increased, hypotension (13%), anemia, thrombocytopenia, alanine aminotransferase increased (11%), infection, dehydration, dyspnea (9%), lymphopenia, neutropenia, hyperbilirubinemia, hypocalcemia, hypoxia (6%), febrile neutropenia, leukopenia, ventricular arrhythmia, vomiting, hypersensitivity, catheter related infection, hyperuricemia, hypoalbuminemia, syncope, pneumonitis, packed red blood cell transfusion, and platelet transfusion (4%).

In an animal reproductive study, romidepsin was embryocidal and resulted in adverse effects on the developing fetus at exposures below those in patients at the recommended dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus. Romidepsin was administered intravenously to rats during the period of organogenesis at doses of 0.1, 0.2, or 0.5 mg/kg/day. Substantial resorption or post-implantation loss was observed at the high-dose of 0.5 mg/kg/day, a maternally toxic dose. Adverse embryo-fetal effects were noted at romidepsin doses of ≥0.1 mg/kg/day, with systemic exposures (AUC) ≥0.2% of the human exposure at the recommended dose of 14 mg/m2/week. Drug-related fetal effects consisted of folded retina, rotated limbs, and incomplete sternal ossification. 8.3 Nursing Mothers It is not known whether romidepsin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Deaths due to all causes within 30 days of the last dose of ISTODAX occurred in 7% of patients in Study 3 and 17% of patients in Study 4. In Study 3, there were 5 deaths unrelated to disease progression that were due to infections, including multi-organ failure/sepsis, pneumonia, septic shock, candida sepsis, and sepsis/cardiogenic shock. In Study 4, there were 3 deaths unrelated to disease progression that were due to sepsis, aspartate aminotransferase elevation in the setting of Epstein Barr virus reactivation, and death of unknown cause.

8.5 Geriatric Use Of the approximately 300 patients with CTCL or PTCL in trials, about 25% were >65 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; however, greater sensitivity of some older individuals cannot be ruled out. 8.6 Hepatic Impairment No dedicated hepatic impairment study for ISTODAX has been conducted. Mild hepatic impairment does not alter pharmacokinetics of romidepsin based on a population pharmacokinetic analysis. Patients with moderate and severe hepatic impairment should be treated with caution [See Clinical Pharmacology (12.3)]. 8.7 Renal Impairment No dedicated renal impairment study for ISTODAX has been conducted. Based upon the population pharmacokinetic analysis, renal impairment is not expected to significantly influence drug exposure. The effect of end-stage renal disease on romidepsin pharmacokinetics has not been studied. Thus, patients with end-stage renal disease should be treated with caution [See Clinical Pharmacology (12.3)]. 10 OVERDOSAGE No specific information is available on the treatment of overdosage of ISTODAX. Toxicities in a single-dose study in rats or dogs, at intravenous romidepsin doses up to 2.2 fold the recommended human dose based on the body surface area, included irregular respiration, irregular heart beat, staggering gait, tremor, and tonic convulsions. In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., clinical monitoring and supportive therapy, if required. There is no known antidote for ISTODAX and it is not known if ISTODAX is dialyzable. Manufactured for: Celgene Corporation Summit, NJ 07901 Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146 or

Angela Long

Angela Long is the founder and creator of Breast Investigators, which serves as a comprehensive resource guide to help those affected by breast cancer readily gain access to quality information, care, assistance, and support. Visit www. BreastInvestigators.com.

U.S. Patents: 4,977,138; 7,608,280; 7,611,724 ISTBSPTCL.005 06/13

Cosmos Communications

www.TheOncologyNurse.com

A Journey of Discovery When courage, compassion, and connection become a regular practice, they develop into incredible gifts in our life, even when our teacher is cancer. It is through our vulnerabilities that we truly discover these gifts. It takes breaking through our conditioned resistance to vulnerability, removing our protective armor, and allowing others to see who we truly are. While cancer is a physical disease, the scars extend deep into our emotional and spiritual lives. Though never a preferred or desired route, a cancer journey can transform our lives, opening our hearts to new levels of love, joy, and enlightenment. l

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Discontinuations Discontinuation due to an adverse event occurred in 19% of patients in Study 3 and in 28% of patients in Study 4. In Study 3, thrombocytopenia and pneumonia were the only events leading to treatment discontinuation in at least 2% of patients. In Study 4, events leading to treatment discontinuation in ≥2 patients were thrombocytopenia (11%), anemia, infection, and alanine aminotransferase increased (4%). 7 DRUG INTERACTIONS 7.1 Coumadin or Coumadin Derivatives Prolongation of PT and elevation of INR were observed in a patient receiving ISTODAX concomitantly with warfarin. Although the interaction potential between ISTODAX and Coumadin or Coumadin derivatives has not been formally studied, physicians should carefully monitor PT and INR in patients concurrently administered ISTODAX and Coumadin or Coumadin derivatives [See Clinical Pharmacology (12.3)]. 7.2 Drugs that Inhibit Cytochrome P450 3A4 Enzymes Romidepsin is metabolized by CYP3A4. Strong CYP3A4 inhibitors increase concentrations of romidepsin. In a pharmacokinetic drug interaction trial the strong CYP3A4 inhibitor ketoconazole increased romidepsin (AUC0-∞) by approximately 25% [See Clinical Pharmacology (12.3)]. Monitor for toxicity related to increased romidepsin exposure and follow the dose modifications for toxicity [see Dosage and Administration (2.2)] when romidepsin is initially co-administered with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). 7.3 Drugs that Induce Cytochrome P450 3A4 Enzymes Avoid co-administration of ISTODAX with rifampin. In a pharmacokinetic drug interaction trial with co-administered rifampin (a strong CYP3A4 inducer), romidepsin exposure was increased by approximately 80% and 60% for AUC0-∞ and Cmax, respectively [See Clinical Pharmacology (12.3)]. Typically, co-administration of CYP3A4 inducers decrease concentrations of drugs metabolized by CYP3A4. The increase in exposure seen after co-administration with rifampin is likely due to rifampin’s inhibition of an undetermined hepatic uptake process that is predominantly responsible for the disposition of ISTODAX. It is unknown if other potent CYP3A4 inducers (e.g., dexamethasone, carbamazepine, phenytoin, rifabutin, rifapentine, phenobarbital, St. John’s Wort) would alter the exposure of ISTODAX. Therefore, the use of other potent CYP3A4 inducers should be avoided when possible. 7.4 Drugs that Inhibit Drug Transport Systems Romidepsin is a substrate of the efflux transporter P-glycoprotein (P-gp, ABCB1). If ISTODAX is administered with drugs that inhibit P-gp, increased concentrations of romidepsin are likely, and caution should be exercised. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category D [See Warnings and Precautions (5.5)]. There are no adequate and well-controlled studies of ISTODAX in pregnant women. However, based on its mechanism of action and findings in animals, ISTODAX may cause fetal harm when administered to a pregnant woman.

8.4 Pediatric Use The safety and effectiveness of ISTODAX in pediatric patients has not been established.

tion helped me to start processing my own journey, but even within the cancer community, survivors can have a difficult time finding connection. Jamie, a stage IV Hodgkin lymphoma survivor, commented, “Being a single young woman with cancer was awful, and I had no support or guidance. Since I didn’t have one of the more common female cancers, I had nobody to relate to during that time. I felt extremely alone.” A cancer diagnosis shows us who we can lean on without judgment or pity and those we cannot lean on at all. Vulnerability can act as a filter in this respect. It is typically transformational with all relationships, resulting in a strengthening of some relationships and dissolution of others. Trust is the foundation. Without trust, we cannot be honest about our feelings of vulnerability, and without honesty, we cannot feel genuinely connected to others.

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The Other Side of the Stethoscope Continued from cover and going to yoga. I had a normal primary doctor visit in November 2009 with a normal pelvic and rectal exam. So why, I wondered over March and April in 2010, was I not losing weight and did my pants seem tighter? I think I said something maybe a year before about bloating and all my weight going to the middle—but that was just “becoming matronly”—you know, the menopause thing. I just needed to watch my diet, drink less wine, and exercise correctly, right? And the indigestion, well what do you want when you eat cold food in fast bites between patients and charting or dictating? I had the same thing off and on over the years. Doesn’t everyone have TUMS in their work bag or glove compartment? The first week of May in 2010 I felt like my clothes were really tight. After coming home from a Saturday overnight shift, I finally laid down on the bed and palpated my abdomen. Uh oh, I thought, that feels like a mass. So I slept my usual 5 or 6 hours in the morning, but when I checked again Sunday afternoon, it was still there—making my first hope that it was a lump of stool less likely. OK, I’m thinking, what are the possibilities? Maybe it’s just a giant fibroid; it was a middle to right-sided mass that I could feel and was quite firm. Or, could it be colon cancer—I was overdue for another colonoscopy, but I had no polyps or anything amiss in 2003. Or, worst case scenario, ovarian cancer. Yes, I thought of it, but at that point, that was a death sentence in my mind and not an option I wanted to consider. I knew there was no breast, ovarian, or colon cancer in my family but that wasn’t enough. I didn’t say anything at home because I didn’t know very much; I just had worries. First thing the next day, Monday, May 10, I called my primary doctor and left a message with the office staff to tell her that “I felt a mass in my abdomen.” That caught her attention and she added me in at noon. She didn’t say much after my pelvic exam, but labs including CA-125 were ordered, drawn that day, and a request for an ultrasound was sent. I scheduled my ultrasound for the next morning. Tuesday, May 11, I

Tania Homonchuk and her family.

was at the community radiology center—they asked if I minded a student doing the exam. No problem, been there. But after a minute, the regular tech comes in and takes over—not a good sign. Transabdominal and intravaginal US, and hmmm, why were they doing extra views that I know are for intra-abdominal fluid? Thankfully the

which confirmed and defined the extent of my disease. No invasion of the liver or lungs but huge ovarian tumors, a coating of metastases on virtually everything else, and a large amount of ascites in the abdomen. I had also learned that my CA-125 was 2900, which was sky high. How do you deal with all of that? This is stuff that happens to other people. I

In all women the bloating, indigestion, back pain, or other miscellaneous “not feeling right” complaints certainly merit a closer look and at least inclusion of ovarian cancer in the differential.

radiologist had me come in to review the ultrasound and talk with me. He was very direct and told me that widespread ovarian cancer was the most likely diagnosis. He called my primary doctor while I was there, and she arranged insurance approval for a contrast CT that same afternoon. However, in the meantime I was in shock—I have metastatic ovarian cancer, I am going to die. I went home in tears to tell my husband. I went back for the CT in the afternoon,

went to my son’s track meet that same afternoon, and had several people comment that I was quiet—just tired from work I said. My primary doctor arranged a referral to a gynecologic oncologist the very next day. She fit me in quickly as a referral, and it didn’t matter that I had to wait a couple of hours in the office, because I was scared stiff. After a discussion of my cancer (I was stage 3C) and the options, the plan was urgent surgery followed by chemo. This was on

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Wednesday, May 12. My husband was due to go out of town on family business that Friday but the doctor wanted to do surgery on Monday. So he went the next day on May 13—which happened to be our anniversary—and returned on Saturday. Meanwhile, I was the organizer for an awards banquet that night at the high school, my younger son had his first AP exams that week, and the older one had finals week at Cal. How do you tell your kids you have cancer? There is no easy way and certainly no good time. Or as one friend pointed out when I worried about it, there just is no good time to have cancer. But the week went on, both boys were told in person, we did an online will—you know, one of those things you keep meaning to get around to—and I did the prep for surgery on Monday, May 17. The signs and symptoms of metastatic ovarian cancer were nothing for so long. I was menopausal, so bloating was nothing I paid attention to nor was indigestion. In retrospect, the eating less was probably early satiety. No pain until the day or two before surgery and not bad then. The tight pants and increased girth were partly mass and partly fluid— and at that point I was already in a late stage. However, in 1 week I went from feeling a mass to having surgery, and I am ever so grateful that my primary doctor saw me urgently and paid attention to my call, to the radiologist for including me in the verbal report and discussion with my primary doctor, and for the immediate referral to a gynecologic oncology specialist who saw me right away. I am very lucky in that regard, or I might not be here today to tell this story. Paying attention to those nonspecifics in women is important— like the “I just feel tired” complaint I hear from an 80-year-old woman that really is a heart attack. In all women the bloating, indigestion, back pain, or other miscellaneous “not feeling right” complaints certainly merit a closer look and at least inclusion of ovarian cancer in the differential. My journey since diagnosis has been chock-full of experiences on the patient side of things. First surgery with tumor removal, hysterectomy-oophorectomy, splenectomy, descending colon resection, appendectomy, node resection, omentectomy, and stripping of the bladder, ureters, and liver. I woke up in the ICU a day and a half later and 30 pounds lighter when they turned down the propofol drip. I was intubated, with an IJ central line, and later a PIC line, peripheral IV sites, multiple drains, Foley, and NG tube. No way was I rolling over, much less sit, stand, or walk. But it all happens. The nursing care was so important: first the focus on small

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THE PATIENT’S VOICE steps and then getting stronger to get on with the rest of the treatment. And the recognition that this was a scary time with so many unknowns, that empathy, meant a lot to me. I had a port placed and 6 months of chemo 3 weeks out of 4 with dose-dense taxol and carboplatin, and then IP or intraperitoneal chemo was planned. I lost my hair, which for me was a much more “in your face” reminder that I had cancer, and was fatigued. Still I gradually went back to long walks with the dog, yoga, and exercise. I did read about and take advantage of supplements and had acupuncture prior to chemo. My chemo was given at the gynecology-oncology office, which for me was a good sharing time. In the chemo room it was all women with gynecologic cancers, and the camaraderie was appreciated. The nursing care was focused on women with these cancers and associated treatments.

Think about how you would want to be treated as a patient—it is very different on the other side.

few weeks of fear. On the other hand, most of the time it is not on my mind. I returned to work part time and family life continues. But my perspective is certainly different. I also have tried to give back a bit and look to the future for ovarian cancer treatment. I am participating in the Survivors Teaching Students program of the Ovarian Cancer National Alliance, to tell our stories to nursing

and medical students and get the word out about the nonspecific signs and symptoms as well as the importance of risk factors and of having a gynecologic oncologist. I also have been fundraising with the Clearity Foundation, which helps women with resistant or recurrent ovarian cancer get genetic typing or blueprints of their cancer. This provides personalized information about the best treatment

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However in October during laparoscopy for abdominal port placement, I had too much scarring for IP chemo, so back I went to the drawing board. I opted for a second surgery after discussion with an oncologic surgeon who was recommended by my main gynecologic oncologist. Off of chemo for 2 months in preparation, in January 2011 I had a second major surgery with adhesion removal that freed up the intestines and liver, a periaortic node resection, resection of the cecum because it was adhered due to scar tissue, removal of the gallbladder, and multiple node biopsies. All were clean. Then heated intraperitoneal cisplatin in the OR—40-degree chemo swished around for a couple hours does a number on the GI tract! Another couple of days in the ICU, more drains, gastrostomy tube (which, by the way, was actually nicer than the NG tube, even if I did feel like a nursing home patient), subclavian line, then PIC again, and eventually recovery. Every 3 months I get my CA-125 and exam and have had a couple of follow-up MRI scans. So far so good, and I am thrilled to make the 2-year mark disease-free. But every 3 months I go into a couple weeks of building anxiety—what will my number be? And is that indigestion just indigestion? I have multiple sizes of jeans under the bed just in case I need them again. It really becomes a

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options for this disease that is so often diagnosed in a late stage and is so often recurrent. I encourage you to think about nonspecific symptoms differently and keep ovarian cancer in mind—it is so silent and for many the journey to diagnosis is long and arduous. And as a provider, think about how you would want to be treated as a patient—it is very different on the other side. l

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