OPM June 2015 | Vol 5 | No 5 by Value-Based Cancer Care

June 2015

www.OncPracticeManagement.com

Title

Volume 5 • Number 5

Oncology Practice Management ™

FOR ONCOLOGISTS, PRACTICE MANAGERS, FINANCIAL COUNSELORS, AND REIMBURSEMENT SPECIALISTS™

Pathways versus Personalized Medicine By Gail Thompson

The State of Side-Effect Management for Our Patients By Sheryl A. Riley, RN, OCN, CMCN

he goal of cancer treatment is to destroy cancer cells, whether through surgery, radiation, drug therapies, or a combination of these. During the course of these treatments, however, healthy cells can also be damaged or destroyed, leading to unpleasant side effects such as electrolyte imbalance, dehydration, weight loss, fatigue,

infection, lack of appetite, mouth sores, skin irritations, anemia, and depression. These side effects can frighten and even terrify patients if they have not been educated on what to expect; withContinued on page 20

Michael Kolodziej, MD, FACP

articipants at the 2015 Association for Value-Based Cancer Care annual meeting were challenged to consider the concept of value in oncology, and whether providers are truly delivering oncology care that serves society and patients with cancer. After hinting that pathways and next-generation sequencing are good steps but not the ultimate solutions, Michael Kolodziej, MD, FACP, National Medical Director, On-

Insurance Status Linked to Higher Rates of Certain Cancer Types By Rosemary Frei, MSc

ninsured Americans and those with Medicaid insurance are more likely to be younger, nonwhite, unmarried, and live in rural areas than those with non-Medicaid insurance, according to a study recently published in Cancer.1 Furthermore,

despite the extension of Medicaid eligibility to women diag- Usama Mahmood, MD nosed with breast and cervical cancer in the Breast and Cervical Cancer Prevention and Treatment Act of 2000,

Continued on page 8

Continued on page 10 From the publishers of

INTEGRATING ONCOLOGISTS, PAYERS, AND THE ENTIRE CANCER CARE TEAM

ith 9 st w …3 n a t l tie lom a a P e ic or My f n s li al le c Tri ltip u M

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Trusted to take a bite out of G-CSF acquisition costs

GRANIX® has gained >34% share of the US short-acting G-CSF hospital market in its first 17 months1 » A 71% reduction in duration of severe neutropenia vs placebo (1.1 days vs 3.8 days, p<0.0001)2 – 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)2 » The safety of GRANIX was established in 3 Phase III trials, with 680 patients receiving chemotherapy for either breast cancer, lung cancer, or non-Hodgkin lymphoma (NHL)2 » Offering a presentation for self-administration

Indication » GRANIX 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. » 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. » Capillary leak syndrome (CLS): CLS can occur in patients receiving hG-CSFs and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of CLS should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. » 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. » 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. *Based on wholesale acquisition cost (WAC) of all short-acting G-CSF products as of March 2015. WAC represents published catalogue or list prices and may not represent actual transactional prices. Please contact your supplier for actual prices. References: 1. This information is an estimate derived from the use of information under license from the following IMS Health Information Service: IMS National Sales Perspective, GRANIX micrograms by non-federal hospital channel March 2015. IMS expressly reserves all rights, including rights of copying, distribution, and republication (micrograms calculated as eaches x strength). 2. GRANIX® (tbo-filgrastim) Injection Prescribing Information. North Wales, PA: Teva Pharmaceuticals; 2014.

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 nonmyeloid 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 Capillary Leak Syndrome Capillary leak syndrome (CLS) can occur in patients receiving human granulocyte colonystimulating factors and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. 5.6 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)] • Capillary Leak Syndrome [see Warnings and Precautions (5.5)] • Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions (5.6)] 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 non-US-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 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-USapproved 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. Additional Adverse Reactions Other adverse reactions known to occur following administration of human granulocyte colony-stimulating factors include myalgia, headache, vomiting, Sweet’s syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis and thrombocytopenia. 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 Risk Summary There are no adequate and well-controlled studies of GRANIX in pregnant women. In animal reproduction studies, treatment of pregnant rabbits with tbo-filgrastim resulted in increased spontaneous abortion and fetal malformations at systemic exposures substantially higher than the human exposure. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data In an 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 (AUC) 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. ©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd. Manufactured by: Distributed by: Sicor Biotech UAB Teva Pharmaceuticals USA, Inc. Vilnius, Lithuania North Wales, PA 19454 U.S. License No. 1803 Product of Israel GRX-40581 January 2015 This brief summary is based on TBO-004 GRANIX full Prescribing Information.

Table of Contents

PUBLISHING STAFF Senior Vice President/Group Publisher Nicholas Englezos nenglezos@the-lynx-group.com Vice President/Group Publisher Russell Hennessy rhennessy@the-lynx-group.com Publisher Cristopher Pires cpires@the-lynx-group.com Vice President/Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Director, Client Services Zach Ceretelle zceretelle@the-lynx-group.com Senior Editorial Director Dalia Buffery dbuffery@the-lynx-group.com Editorial Director Anne Cooper acooper@the-lynx-group.com Copyeditor Hina Khaliq Senior Production Manager Lynn Hamilton

The Lynx Group

President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Human Resources Jennine Leale Director, Strategy & Program Development John Welz Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistants Lora LaRocca Wayne Williams Content Marketing Director Samantha Weissman Web Content Manager Anthony Trevean Content Digital Manager Allison Musante Digital Programmer Michael Amundsen Jr Digital Media Specialist Charles Easton IV Meeting & Events Planner Linda Mezzacappa Project Managers Deanna Martinez Jeremy Shannon Project Coordinator Rachael Baranoski IT Manager Kashif Javaid Sales Assistant Aadam Mohamed Administrative Assistant Amanda Hedman Office Coordinator Robert Sorensen Engage Healthcare Communications 1249 South River Road - Ste 202A Cranbury, NJ 08512 phone: 732-992-1880 fax: 732-992-1881

June 2015 • Volume 5 • Number 5

Oncology Practice Management ™

FOR ONCOLOGISTS, PRACTICE MANAGERS, FINANCIAL COUNSELORS, AND REIMBURSEMENT SPECIALISTS™

From The Editor Preparing for Implications of USP 797 and USP 800............................... 7 By Dawn Holcombe, MBA, FACMPE, ACHE, and Willis Triplett, PharmD

Features Association for Value-Based Cancer Care Pathways versus Personalized Medicine.............................................1 By Gail Thompson

Cancer Care The State of Side-Effect Management for Our Patients.................. 1 By Sheryl A. Riley, RN, OCN, CMCN

Insurance Status Linked to Higher Rates of Certain Cancer Types.........................................................................................1 By Rosemary Frei, MSc

Medicare Reimbursement US Oncologists Favor Establishment of NICE-Like Body to Determine Medicare Reimbursement...............................................24 By Rosemary Frei, MSc

Patient Support Future of Patient Support Services Offers Challenges, Opportunities........................................................................................26 By Rosemary Frei, MSc

Human Resources Men and Women in the Workforce: What Has Changed?............. 29 By Ruth Linné Lander, FACMPE Continued on page 6

Mission Statement Oncology healthcare requires providers to focus attention on financial concerns and strategic decisions that affect the bottom line. To continue to provide the high-quality care that patients with cancer deserve, providers must master the ever-changing business of oncology. Oncology Practice Management™ offers process solutions for members of the cancer care team—medical, surgical, and radiation oncologists, as well as executives, administrators, and coders/billers—to assist them in reimbursement, staffing, electronic health records, REMS, and compliance with state and federal regulations. Postmaster: Correspondence regarding subscriptions or change of address should be directed to CIRCULATION DIRECTOR, Oncology Practice Management™, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Fax: 732-992-1881. Yearly subscription rates: 1 year: $99.00 USD; 2 years: $149.00 USD; 3 years: $199.00 USD.

Oncology Practice Management

I June 2015

You put a lot of work into your treatment plan. We’ll do everything we can to support it.

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

Table of Contents

June 2015 • Volume 5 • Number 5

Oncology Practice Management™, ISSN 2164-4403 (print), is published 10 times a year by Engage Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Copyright © 2015 by Engage Healthcare Communications, LLC. All rights reserved. Oncology Practice Management™ is a trademark of Engage Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or here after 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. The ideas and opinions expressed in Oncology Practice Management™ do not necessarily reflect those of the editorial board, the editors, or the publisher. Publication of an advertisement or other product mentioned in Oncology Practice Management ™ should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturers about any features or limitations of products mentioned. Neither the editors nor the publisher assume any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material mentioned in this publication.

Oncology Practice Management ™

FOR ONCOLOGISTS, PRACTICE MANAGERS, FINANCIAL COUNSELORS, AND REIMBURSEMENT SPECIALISTS™

Continued from page 4

DEPARTMENTS Wealth Management Common Deductions Taken by Aggressive Taxpayers.....................34 By Andrew D. Schwartz, CPA, and Lawrence B. Keller, CFP, CLU, ChFC, RHU, LUTCF

Patient and Provider Access SGR Is Over: What’s Next for Providers?...............................................38 By Maureen Leddy, JD

Clinical Trial Tracker Trials for Patients with Multiple Myeloma.............................................39 Drug Update Jakafi (Ruxolitinib): First FDA-Approved Medication for the Treatment of Patients with Polycythemia Vera..................................43 By Lisa A. Raedler, PhD, RPh

Drug Coding FDA-Approved Medications Used for the Treatment of Lung Cancer............................................................................................55

Editorial Advisory Board Editor-in-Chief Dawn Holcombe, MBA, FACMPE, ACHE President DGH Consulting South Windsor, CT Carla Balch CEO, Altos Solutions a Division of Flatiron Health, Inc New York, NY Peggy Barton, RN Practice Manager Toledo, OH

Risë Marie Cleland President Oplinc, Inc Portland, OR Teri U. Guidi, MBA, FAAMA President and CEO Oncology Management Consulting Group Pipersville, PA Mariana Lamb, MS Executive Director Medical Oncology Association of Southern California Upland, CA

Oncology Practice Management

I June 2015

Bonnie J. Miller, RN, BSN, OCN, FAAMA Administrative Director Women’s Cancer Center Fox Chase Cancer Center Philadelphia, PA Karna W. Morrow, CPC, RCC, CCS-P, PCS Senior Consultant CSI Coding Strategies, Inc Powder Springs, GA

Robert D. Orzechowski, MBA, SPHR Chief Operating Officer Lancaster Cancer Center Lancaster, PA Nancy G. Payne, CMPE Executive Director Space Coast Cancer Center Titusville, FL Sheryl A. Riley, RN, OCN, CMCN Director of Clinical Services SAI Systems Shelton, CT

From the Editor

Preparing for Implications of USP 797 and USP 800 By Dawn Holcombe, MBA, FACMPE, ACHE; President, DGH Consulting, South Windsor, CT; Editor-in-Chief, Oncology Practice Management; and Willis Triplett, PharmD

f your practice or cancer center receives, handles, stores, compounds, dispenses, administers, or disposes of hazardous drugs, you may soon be affected by the US Pharmacopeial Convention’s General Chapter 800 Hazardous Drugs— Handling in Healthcare Settings (USP 800). It will affect different practices in different ways, depending on how it is enforced as well as the agency or organization that may choose to enforce it. A version of USP 800 that was published in 2014 was updated in response to public comments. This newer version was available for further public comment through May 31, and a final version that incorporates public feedback should be published in the near future. General Chapter 797 Pharmaceutical Compounding—Sterile Preparations (USP 797) also may have an impact on oncology practices and cancer centers. It was published in 2004 and was most recently revised in 2008. An expert panel was convened in April 2013 to review further changes to this chapter. Both USP 797 and USP 800 are considered enforceable by entities, including the US Food and Drug Administration, Occupational Safety & Health Administration, state boards of pharmacy, and even state legislatures. Historically, USP 797 has not been applied to cancer centers and oncology practices because of the individual and short-term duration of their drug compounding. However, some clinical trial organizations are now seeking to restrict trial activity only to cancer centers that are compliant with USP 797.

This could have widespread impact on private practices and cancer centers if it is expanded, as most clinical trials currently are taking place in the outpatient setting.

can be an isolated, restricted-traffic room just large enough to house a containment primary engineering control and an operator wearing adequate gowning, garb, and personal protective equipment. The proposed USP 800 stipulates that a C-SCA must meet criteria specific to ventilation and airflow. If a cancer center cannot adhere to a 12-hour beyond- use date, however, then its only means to compliance will be to construct or gain the use of a fully functional clean room. The physical facility requirement is just one aspect of USP 797 and proposed USP 800, and both chapters present myriad other requirements related to the communication and understanding of policies and procedures, training of team members, environmental certification requirements for a clean room, and effective quality management programs. The comment period for USP 800 just passed, and we are awaiting a final determination; however, we have seen individual state boards of pharmacy, state legislatures, the Occupational Safety & Health Administration, and clinical trial organizers start to mandate some degree of compliance with USP 797. This is an issue that will continue to expand and will affect practices and cancer centers across the country in varying degrees. Compliance audits of clinics and practices have already started and revealed oversights even in the most conscientious facilities. Oncology practices and cancer centers should begin preparations now in anticipation of these regulations. l

What would oncology practices and cancer centers need to become compliant with USP 797 and USP 800? Most oncology practices would need a clean room that complies with the individual requirements of these chapters, but would face a substantial capital expenditure to build one. An affordable alternative might be to lease a temporary or portable clean room, which would allow expenses to be paid from operating revenue; it is important to note, however, that clean rooms that comply with both chapters are expensive. USP 797 and the proposed USP 800 do not actually require a clean room for medical practices if the practice can limit itself to starting the infusion of its compounded sterile products within 12 hours of completing the compound. If a practice can meet that stipulation, it can be compliant by limiting its compounding to a containment segregated compounding area (C-SCA). This

June 2015

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Association for Value-Based Cancer Care

Pathways versus Personalized Medicine Continued from the cover cology Solutions, Aetna, explained his reasoning. “We’re in this big discussion now,” he said. “What constitutes value in oncology? You can turn this around any which way you like, but ultimately what we really want to have is the best possible outcome for our patients at a fair price. I didn’t say cheap, I said fair.” Dr Kolodziej recognized the commonly acknowledged costs of cancer care, noting that almost every discussion begins with conversations

He acknowledged that cancer drugs are expensive, and that the cost escalation of cancer care is so much faster than other elements of the US economy that it is dragging down productivity and profitability in the private sector. These concerns, however, present only half the story, he said, citing a recent study published in JAMA Oncology that determined a low correlation between the prices of oncology drugs at the time of their commercialization and disease responses to therapy. His

“You can turn this around any which way you like, but ultimately what we really want to have is the best possible outcome for our patients at a fair price.” —Michael Kolodziej, MD, FACP

about the rapid growth of cancer care costs compared with the cost of healthcare premiums, general medical care costs, or the growth of the US economy. The scenario is frequently described as unsustainable, and the challenge, Dr Kolodziej added, is not just the cost of care, but the perception that patients are not experiencing good outcomes despite all the money being spent on treatment.

concern, and that of the study authors, was that this indicated that drug prices were determined more by what the market will bear, rather than the benefit the drug brings to patients and society. Turning to pathways, Dr Kolodziej shared a former advertisement for Marlboro cigarettes, pointing to the man in the advertisement to illustrate the difficulty in assessing appropriate treatment options for patients

KEY POINTS n Pathways have become a key element of population management, but they come with challenges n Costs of care may vary between patients with the same diagnosis depending on their age, health status, and therapy needs n Pathways have the potential to promote personalized therapy that is not just based upon genomic sequencing, but on many patient characteristics

Oncology Practice Management

I June 2015

as well as the role of pathways in patient care. The image illustrates both the fallacy behind the idea of N-of-1, he said, as well as the idea of a master clinician, who can determine appropriate treatments by simply looking at a patient. “There is no oncologist in the universe who can look at that patient and decide which of the drugs… are best for [him],” Dr Kolodziej said. “The truth of the matter is we need a construct to identify the right way to treat the Marlboro man.” Pathways have become a key element of population management that define the best treatment for the average patient, he said. Pathways do come with challenges, he noted; national payers seem to be embracing them, local payers are not embracing them as quickly, and providers are embracing pathways that have been developed internally. This is a point of concern, Dr Kolodziej said, since many practices do not have a formal process to weigh evidence, or a way to track evidence and utilize it at the point of care. There must also be a mechanism for documenting medical decisions, as well as medical and financial consequences of those decisions. He stressed the value of a formal pathway program that provides the ability to measure performance, look for opportunities for improvement, and improve processes of care. Costs of care may vary between patients with the same diagnosis depending on their age, health status, and therapy needs, he stated, and it is important to sort patients by their clinical features and cost profiles as reimbursement models inevitably shift to episode-based payments. Pathways are necessary, he said, to lay the groundwork for this evolving reimbursement model. “Without a pathways-type construct,” he said, “we will never get to

Association for Value-Based Cancer Care

the point where anybody will be able to project what an episode-based reimbursement might look like. That’s why we need pathways now.”

Oncology examining 647 patients who were slotted into 5 biomarker- matched treatment groups. Ultimately, what seemed to be standard

lation models and pathways may allow the organization and alignment of complex data. Pathways have the potential to promote personalized therapy that is not just based upon genomic sequencing, but on many patient characteristics. The challenge will be to develop technology, tracking, and reporting that takes solutions that may be hidden within data to help physicians make decisions at the point of care. “We need the ability to sort a population into the just-right size that has traditional clinical markers, where we understand the cost of care, where we put in molecular markers, and we make an intervention and can measure what happens,” Dr Kolodziej said. “Pathways are just a way of structuring complex data from multiple inputs at the point of care. That’s all it is…it’s all about thinking about all those variables and giving them common structure.” l

“Pathways are just a way of structuring complex data from multiple inputs at the point of care. That’s all it is…it’s all about thinking about all those variables and giving them common structure.” —Michael Kolodziej, MD, FACP

Dr Kolodziej suggested that treatment choices solely related to epidermal growth factor receptor (EGFR) mutations do not necessarily provide the best clinical outcome for a patient, noting that deletions and point mutations must also be taken into consideration when determining therapeutic options. He referred to a recent phase 2 study that was reported in the Journal of Clinical

indications for specific treatments based upon markers determined by genomic sequencing led to treatments that did not produce the expected outcomes. The solution, he said, may be to identify appropriate subpopulations that will allow a determination of the likelihood of response based on patient characteristics and clinical elements. The use of different popu-

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Cancer Care

Insurance Status Linked to Higher... Continued from the cover women with cervical cancer have one of the highest rates of being uninsured among patients with cancer. Patients with testicular and stomach cancers are also likely to be uninsured. The authors indicate that further efforts may improve awareness and accessibility of care for these patients, and that continuing research will help clarify the impact of recent legislative efforts to increase the number of people with insurance coverage.

who were diagnosed with the 25 most common types of cancer between 2007 and 2010 and who were uninsured, had non-Medicaid insurance (ie, private insurance, Medicare, or insurance from the military or Department of Veterans Affairs), or Medicaid insurance. The rate of non-Medicaid insurance coverage among white patients (87.4%) was second only to the rate among a small number of patients who

“Our role as oncologists is to, as best as we can, monitor these changes and help ensure the best outcomes possible for our patients.”

—Usama Mahmood, MD

“Additional efforts may help to expand access to care among patients with those cancer types and demographic groups with the highest rate of uninsurance,” wrote Usama Mahmood, MD, and colleagues. They also noted that “with such wide discrepancies in insurance coverage, the PPACA [Patient Protection and Affordable Care Act] will disproportionately benefit certain populations,” although “further research will be needed to determine whether and to what extent cancer care is ultimately impacted by the upcoming changes in insurance coverage.” Dr Mahmood, Assistant Professor, Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, and colleagues used the Surveillance, Epidemiology, and End Results (SEER) database in their study to determine the association between demographics and insurance status among patients with cancer. They identified 646,611 patients aged 18 to 64 years

indicated their race was unknown (91.1%), while rates of Medicaid insurance coverage were highest among American Indian/Alaska Native patients. Rates of uninsured patients were highest among Hispanic patients. Moreover, the rate of non-Medicaid insurance coverage fell from 79.1% in 2007 to 76.2% in 2010, whereas in this time frame the rate of uninsured patients rose from 4.8% to 5.1%. The authors posited that the latter increase was likely because of an economic downturn during that period. The investigators’ multivariate analysis showed that younger age, nonwhite race, and being unmarried were among the factors associated with a greater probability of patients being uninsured or having Medicaid insurance compared with patients having non-Medicaid insurance. Furthermore, among the top 25 most common cancer types, those types with the highest proportion of uninsured patients were testicular cancer (10.5%), stomach cancer (9.7%), and cervical cancer (8.9%). The lowest

Oncology Practice Management

I June 2015

rates of uninsured patients were found among those with thyroid cancer (3.2%), prostate cancer (2.7%), and breast cancer (2.6%). The highest rates of Medicaid insurance coverage were among patients with cervical cancer (27.0%), liver cancer (24.1%), and vulvar cancer (20.3%), whereas the highest rates of non-Medicaid insurance coverage were among patients with prostate cancer (92.3%), skin melanoma (92.5%), and thyroid cancer (89.5%). Among patients without insurance and patients with Medicaid, the most common causes of cancer mortality were lung, colorectal, and liver cancers. In patients with non-Medicaid insurance, the most common causes of cancer mortality were lung, pancreatic, and colorectal cancers. Among all 3 insurance categories, patients with lung cancer presented the highest estimated annual mortality burden, exceeding the combined mortality burden of the next 4 most common causes of cancer mortality. Generally, expanded insurance coverage offered through PPACA will likely impact certain patient populations more than others. Researchers concluded that more research will be warranted once PPACA is fully implemented to further examine the trends found in this first analysis of insurance status differences among patients with cancer in the SEER database. “Time will tell how the incidence and mortality of the individual cancers will be impacted by the full rollout of the PPACA,” Dr Mahmood told Oncology Practice Management. “And our role as oncologists is to, as best as we can, monitor these changes and help ensure the best outcomes possible for our patients.” l Reference

1. Grant SR, Walker GV, Guadagnolo BA, et al. Variation in insurance status by patient demographics and tumor site among nonelderly adult patients with cancer. Cancer. 2015 Apr 27 [Epub ahead of print].

In men with mCRPC who progressed on ADT

The story for ZYTIGA® has significantly evolved. Presenting…

mCRPC = metastatic castration-resistant prostate cancer; ADT = androgen-deprivation therapy.

INDICATION ZYTIGA® (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

IMPORTANT SAFETY INFORMATION Contraindications—ZYTIGA® is not indicated for use in women. ZYTIGA® can cause fetal harm (Pregnancy Category X) when administered to a pregnant woman and is contraindicated in women who are or may become pregnant. Hypertension, Hypokalemia, and Fluid Retention Due to Mineralocorticoid Excess—Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in blood pressure, hypokalemia, or fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) because these patients were excluded from these randomized clinical trials. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly. Adrenocortical Insufficiency (AI)—AI was reported in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations. Hepatotoxicity—Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). Measure serum transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function. Please see additional Important Safety Information on the next pages. Please see brief summary of full Prescribing Information on subsequent pages.

In men with mCRPC who progressed on ADT, consider ZYTIGA® (abiraterone acetate) first.

Final analysis of the pivotal phase 3 trial.*

Every day tells a story.

IMPORTANT SAFETY INFORMATION Increased ZYTIGA® Exposures With Food—ZYTIGA® must be taken on an empty stomach. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state. Adverse Reactions—The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and contusion. The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT, and hypokalemia. *Study Design: ZYTIGA®, in combination with prednisone, was evaluated in a phase 3, randomized, double-blind, placebo-controlled, multicenter trial in patients with mCRPC who had not received prior chemotherapy (N=1,088). Patients were using a luteinizing hormone-releasing hormone (LHRH) agonist or were previously treated with orchiectomy. In the ZYTIGA® arm, patients received ZYTIGA® 1,000 mg orally once daily + prednisone 5 mg orally twice daily. In the placebo arm, patients received placebo orally once daily + prednisone 5 mg orally twice daily. In this study, the co-primary efficacy end points were OS and radiographic progression-free survival (rPFS). Select exclusion criteria included AST and/or ALT ≥ 2.5X ULN, liver metastases, moderate or severe pain, opiate use for cancer pain, and visceral organ metastases. † At a prespecified final analysis for OS, 65% (354/546) of patients treated with ZYTIGA® + prednisone compared with 71% (387/542) of patients treated with placebo + prednisone had died. ‡Prednisone, as a single agent, is not approved for the treatment of prostate cancer. § rPFS was assessed with the use of sequential imaging studies and was defined by bone scan identification of 2 or more new bone lesions with confirmation (Prostate Cancer Working Group 2 [PCWG2] criteria) and/or modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria for progression of soft tissue lesions. Analysis of rPFS utilized centrally reviewed radiographic assessment of progression. IIAt the prespecified rPFS analysis, 150 (28%) of patients treated with ZYTIGA® + prednisone and 251 (46%) of patients treated with placebo + prednisone had radiographic progression.

Janssen Biotech, Inc. © Janssen Biotech, Inc. 2015 3/15 028723-150129

Please see brief summary of full Prescribing Information on subsequent pages.

After a median 4 years (49 months) of follow-up…

ZYTIGA® (abiraterone acetate) + prednisone achieved a median overall survival (OS) of almost 3 years (34.7 months).1† • 4.4 months improvement in median OS—34.7 months with ZYTIGA® + prednisone vs 30.3 months with placebo + prednisone (active compound)‡ Co-primary end point—median OS: hazard ratio (HR)=0.81; 95% CI: 0.70, 0.93; P=0.0033. Co-primary end point—rPFS: median not reached for ZYTIGA® + prednisone vs a median of 8.28 months for placebo + prednisone; HR=0.425; 95% CI: 0.347, 0.522; P<0.0001.§II

With a median 49 months of follow-up, there were no notable changes in the safety profile of ZYTIGA® + prednisone since the previously reported interim analyses.1 In your patients with mCRPC…

Drug Interactions—Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA® treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA® dosing frequency only during the co-administration period [see Dosage and Administration (2.3)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone. ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. Avoid co-administration with CYP2D6 substrates with a narrow therapeutic index. If alternative treatments cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate drug. In a CYP2C8 drug interaction trial in healthy subjects, the AUC of pioglitazone, a CYP2C8 substrate, was increased by 46% when administered with a single dose of ZYTIGA®. Patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA®. Use in Specific Populations—Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C). Reference: 1. Ryan CJ, Smith MR, Fizazi K, et al; for the COU-AA-302 Investigators. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16(2):152-160.

Learn more today at

www.zytigahcp.com.

Every day tells a story.

003307-150130

CONSIDER ZYTIGA® FIRST.

ZYTIGA® (abiraterone acetate) Tablets Brief Summary of Prescribing Information. INDICATIONS AND USAGE ZYTIGA is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer. CONTRAINDICATIONS Pregnancy: ZYTIGA can cause fetal harm when administered to a pregnant woman. ZYTIGA is not indicated for use in women. ZYTIGA is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss [see Use in Specific Populations]. WARNINGS AND PRECAUTIONS Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess: ZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1) in full Prescribing Information]. In the two randomized clinical trials, grade 3 to 4 hypertension occurred in 2% of patients, grade 3 to 4 hypokalemia in 4% of patients, and grade 3 to 4 edema in 1% of patients treated with ZYTIGA [see Adverse Reactions]. Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in the incidence and severity of these adverse reactions. Use caution when treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, e.g., those with heart failure, recent myocardial infarction or ventricular arrhythmia. Use ZYTIGA with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with left ventricular ejection fraction <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) was not established because these patients were excluded from these randomized clinical trials [see Clinical Studies (14) in full Prescribing Information]. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with ZYTIGA. Adrenocortical Insufficiency: Adrenal insufficiency occurred in the two randomized clinical studies in 0.5% of patients taking ZYTIGA and in 0.2% of patients taking placebo. Adrenocortical insufficiency was reported in patients receiving ZYTIGA in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations [see Warnings and Precautions]. Hepatotoxicity: In the two randomized clinical trials, grade 3 or 4 ALT or AST increases (at least 5X ULN) were reported in 4% of patients who received ZYTIGA, typically during the first 3 months after starting treatment. Patients whose baseline ALT or AST were elevated were more likely to experience liver test elevation than those beginning with normal values. Treatment discontinuation due to liver enzyme increases occurred in 1% of patients taking ZYTIGA. No deaths clearly related to ZYTIGA were reported due to hepatotoxicity events. Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced ZYTIGA dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the ULN, or the bilirubin rises above three times the ULN, interrupt ZYTIGA treatment and closely monitor liver function. Re-treatment with ZYTIGA at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN [see Dosage and Administration (2.2) in full Prescribing Information]. The safety of ZYTIGA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown. Increased ZYTIGA Exposures with Food: ZYTIGA must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state. The safety of these increased exposures when multiple doses of abiraterone acetate are taken with food has not been assessed [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

ZYTIGA® (abiraterone acetate) Tablets ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: • Hypertension, Hypokalemia, and Fluid Retention due to Mineralocorticoid Excess [see Warnings and Precautions]. • Adrenocortical Insufficiency [see Warnings and Precautions]. • Hepatotoxicity [see Warnings and Precautions]. • Increased ZYTIGA Exposures with Food [see Warnings and Precautions]. Clinical Trial Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Two randomized placebo-controlled, multicenter clinical trials enrolled patients who had metastatic castration-resistant prostate cancer who were using a gonadotropin-releasing hormone (GnRH) agonist or were previously treated with orchiectomy. In both Study 1 and Study 2 ZYTIGA was administered at a dose of 1,000 mg daily in combination with prednisone 5 mg twice daily in the active treatment arms. Placebo plus prednisone 5 mg twice daily was given to control patients. The most common adverse drug reactions (≥10%) reported in the two randomized clinical trials that occurred more commonly (>2%) in the abiraterone acetate arm were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion. The most common laboratory abnormalities (>20%) reported in the two randomized clinical trials that occurred more commonly (≥2%) in the abiraterone acetate arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia. Study 1: Metastatic CRPC Following Chemotherapy: Study 1 enrolled 1195 patients with metastatic CRPC who had received prior docetaxel chemotherapy. Patients were not eligible if AST and/or ALT ≥2.5 XULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5X ULN. Table 1 shows adverse reactions on the ZYTIGA arm in Study 1 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with ZYTIGA was 8 months. Table 1: Adverse Reactions due to ZYTIGA in Study 1 ZYTIGA with Placebo with Prednisone (N=791) Prednisone (N=394) 1 System/Organ Class All Grades Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Musculoskeletal and connective tissue disorders Joint swelling/ discomfort2 29.5 4.2 23.4 4.1 Muscle discomfort3 26.2 3.0 23.1 2.3 General disorders Edema4 26.7 1.9 18.3 0.8 Vascular disorders Hot flush 19.0 0.3 16.8 0.3 Hypertension 8.5 1.3 6.9 0.3 Gastrointestinal disorders Diarrhea 17.6 0.6 13.5 1.3 Dyspepsia 6.1 0 3.3 0 Infections and infestations Urinary tract infection 11.5 2.1 7.1 0.5 Upper respiratory tract infection 5.4 0 2.5 0 Respiratory, thoracic and mediastinal disorders Cough 10.6 0 7.6 0 Renal and urinary disorders Urinary frequency 7.2 0.3 5.1 0.3 Nocturia 6.2 0 4.1 0 Injury, poisoning and procedural complications Fractures5 5.9 1.4 2.3 0 Cardiac disorders Arrhythmia6 7.2 1.1 4.6 1.0 Chest pain or chest 7 discomfort 3.8 0.5 2.8 0 Cardiac failure8 2.3 1.9 1.0 0.3

ZYTIGA® (abiraterone acetate) Tablets

1 Adverse events graded according to CTCAE version 3.0 2 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness 3 Includes terms Muscle spasms, Musculoskeletal pain, Myalgia,

Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 (continued) ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) 1 System/Organ Class All Grades Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Renal and urinary disorders Hematuria 10.3 1.3 5.6 0.6 Skin and subcutaneous tissue disorders Rash 8.1 0.0 3.7 0.0 1 Adverse events graded according to CTCAE version 3.0 2 Includes terms Edema peripheral, Pitting edema, and Generalized edema 3 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness

Musculoskeletal discomfort, and Musculoskeletal stiffness terms Edema, Edema peripheral, Pitting edema, and Generalized edema 5 Includes all fractures with the exception of pathological fracture 6 Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia 7 Includes terms Angina pectoris, Chest pain, and Angina unstable. Myocardial infarction or ischemia occurred more commonly in the placebo arm than in the ZYTIGA arm (1.3% vs. 1.1% respectively). 8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased 4 Includes

Table 2 shows laboratory abnormalities of interest from Study 1. Grade 3-4 low serum phosphorus (7%) and low potassium (5%) occurred at a greater than or equal to 5% rate in the ZYTIGA arm. Table 2: Laboratory Abnormalities of Interest in Study 1 Abiraterone (N=791) Placebo (N=394) Laboratory All Grades Grade 3-4 All Grades Grade 3-4 Abnormality (%) (%) (%) (%) Hypertriglyceridemia 62.5 0.4 53.0 0 High AST 30.6 2.1 36.3 1.5 Hypokalemia 28.3 5.3 19.8 1.0 Hypophosphatemia 23.8 7.2 15.7 5.8 High ALT 11.1 1.4 10.4 0.8 High Total Bilirubin 6.6 0.1 4.6 0 Study 2: Metastatic CRPC Prior to Chemotherapy: Study 2 enrolled 1088 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥2.5X ULN and patients were excluded if they had liver metastases. Table 3 shows adverse reactions on the ZYTIGA arm in Study 2 that occurred with a ≥2% absolute increase in frequency compared to placebo. The median duration of treatment with ZYTIGA was 13.8 months. Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % General disorders Fatigue 39.1 2.2 34.3 1.7 Edema2 25.1 0.4 20.7 1.1 Pyrexia 8.7 0.6 5.9 0.2 Musculoskeletal and connective tissue disorders Joint swelling/ discomfort3 30.3 2.0 25.2 2.0 Groin pain 6.6 0.4 4.1 0.7 Gastrointestinal disorders Constipation 23.1 0.4 19.1 0.6 Diarrhea 21.6 0.9 17.8 0.9 Dyspepsia 11.1 0.0 5.0 0.2 Vascular disorders Hot flush 22.3 0.2 18.1 0.0 Hypertension 21.6 3.9 13.1 3.0 Respiratory, thoracic and mediastinal disorders Cough 17.3 0.0 13.5 0.2 Dyspnea 11.8 2.4 9.6 0.9 Psychiatric disorders Insomnia 13.5 0.2 11.3 0.0 Injury, poisoning and procedural complications Contusion 13.3 0.0 9.1 0.0 Falls 5.9 0.0 3.3 0.0 Infections and infestations Upper respiratory tract infection 12.7 0.0 8.0 0.0 Nasopharyngitis 10.7 0.0 8.1 0.0

Table 4 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the ZYTIGA arm compared to placebo in Study 2. Grade 3-4 lymphopenia (9%), hyperglycemia (7%) and high alanine aminotransferase (6%) occurred at a greater than 5% rate in the ZYTIGA arm. Table 4: Laboratory Abnormalities in >15% of Patients in the ZYTIGA Arm of Study 2 Abiraterone (N=542) Placebo (N=540) Laboratory Grade 1-4 Grade 3-4 Grade 1-4 Grade 3-4 Abnormality % % % % Hematology Lymphopenia 38.2 8.7 31.7 7.4 Chemistry Hyperglycemia1 56.6 6.5 50.9 5.2 High ALT 41.9 6.1 29.1 0.7 High AST 37.3 3.1 28.7 1.1 Hypernatremia 32.8 0.4 25.0 0.2 Hypokalemia 17.2 2.8 10.2 1.7 1Based on non-fasting blood draws Cardiovascular Adverse Reactions: In the combined data for studies 1 and 2, cardiac failure occurred more commonly in patients treated with ZYTIGA compared to patients on the placebo arm (2.1% versus 0.7%). Grade 3-4 cardiac failure occurred in 1.6% of patients taking ZYTIGA and led to 5 treatment discontinuations and 2 deaths. Grade 3-4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and one death due to cardiac failure in the placebo group. In Study 1 and 2, the majority of arrhythmias were grade 1 or 2. There was one death associated with arrhythmia and one patient with sudden death in the ZYTIGA arms and no deaths in the placebo arms. There were 7 (0.5%) deaths due to cardiorespiratory arrest in the ZYTIGA arms and 3 (0.3%) deaths in the placebo arms. Myocardial ischemia or myocardial infarction led to death in 3 patients in the placebo arms and 2 deaths in the ZYTIGA arms. Post Marketing Experience The following additional adverse reactions have been identified during post approval use of ZYTIGA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Respiratory, Thoracic and Mediastinal Disorders: non-infectious pneumonitis. Musculoskeletal and Connective Tissue Disorders: myopathy, including rhabdomyolysis. DRUG INTERACTIONS Drugs that Inhibit or Induce CYP3A4 Enzymes: Based on in vitro data, ZYTIGA is a substrate of CYP3A4. In a dedicated drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) in full Prescribing Information]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see Clinical Pharmacology (12.3) in full Prescribing Information]. Effects of Abiraterone on Drug Metabolizing Enzymes: ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. In

ZYTIGA® (abiraterone acetate) Tablets

a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3) in full Prescribing Information]. In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA [see Clinical Pharmacology (12.3) in full Prescribing Information].

For patients who develop hepatotoxicity during treatment, interruption of treatment and dosage adjustment may be required [see Dosage and Administration (2.2) in full Prescribing Information, Warnings and Precautions, and Clinical Pharmacology (12.3)] in full Prescribing Information. Patients with Renal Impairment: In a dedicated renal impairment trial, the mean PK parameters were comparable between healthy subjects with normal renal function (N=8) and those with end stage renal disease (ESRD) on hemodialysis (N=8) after a single oral 1,000 mg dose of ZYTIGA. No dosage adjustment is necessary for patients with renal impairment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information]. OVERDOSAGE Human experience of overdose with ZYTIGA is limited. There is no specific antidote. In the event of an overdose, stop ZYTIGA, undertake general supportive measures, including monitoring for arrhythmias and cardiac failure and assess liver function. Storage and Handling: Store at 20°C to 25°C (68°F to 77°F); excursions permitted in the range from 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature]. Based on its mechanism of action, ZYTIGA may harm a developing fetus. Therefore, women who are pregnant or women who may be pregnant should not handle ZYTIGA without protection, e.g., gloves [see Use in Specific Populations]. PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information) • Patients should be informed that ZYTIGA and prednisone are used together and that they should not interrupt or stop either of these medications without consulting their physician. • Patients receiving GnRH agonists should be informed that they need to maintain this treatment during the course of treatment with ZYTIGA and prednisone. • Patients should be informed that ZYTIGA must not be taken with food and that no food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. They should be informed that the tablets should be swallowed whole with water without crushing or chewing. Patients should be informed that taking ZYTIGA with food causes increased exposure and this may result in adverse reactions. • Patients should be informed that ZYTIGA is taken once daily and prednisone is taken twice daily according to their physician’s instructions. • Patients should be informed that in the event of a missed daily dose of ZYTIGA or prednisone, they should take their normal dose the following day. If more than one daily dose is skipped, patients should be told to inform their physician. • Patients should be apprised of the common side effects associated with ZYTIGA, including peripheral edema, hypokalemia, hypertension, elevated liver function tests, and urinary tract infection. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION. • Patients should be advised that their liver function will be monitored using blood tests. • Patients should be informed that ZYTIGA may harm a developing fetus; thus, women who are pregnant or women who may be pregnant should not handle ZYTIGA without protection, e.g., gloves. Patients should also be informed that it is not known whether abiraterone or its metabolites are present in semen and they should use a condom if having sex with a pregnant woman. The patient should use a condom and another effective method of birth control if he is having sex with a woman of child-bearing potential. These measures are required during and for one week after treatment with ZYTIGA.

USE IN SPECIFIC POPULATIONS Pregnancy: Pregnancy Category X [see Contraindications].: ZYTIGA can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no adequate and well-controlled studies with ZYTIGA in pregnant women and ZYTIGA is not indicated for use in women, it is important to know that maternal use of a CYP17 inhibitor could affect development of the fetus. Abiraterone acetate caused developmental toxicity in pregnant rats at exposures that were lower than in patients receiving the recommended dose. ZYTIGA is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with ZYTIGA. In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6-17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients. Nursing Mothers: ZYTIGA is not indicated for use in women. It is not known if abiraterone acetate 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 ZYTIGA, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother. Pediatric Use: Safety and effectiveness of ZYTIGA in pediatric patients have not been established. Geriatric Use: Of the total number of patients receiving ZYTIGA in Phase 3 trials, 73% of patients were 65 years and over and 30% were 75 years and over. No overall differences in safety or effectiveness were observed between these elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Patients with Hepatic Impairment: The pharmacokinetics of abiraterone were examined in subjects with baseline mild (N=8) or moderate (N=8) hepatic impairment (Child-Pugh Class A and B, respectively) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone after a single oral 1,000 mg dose of ZYTIGA increased by approximately 1.1-fold and 3.6-fold in subjects with mild and moderate baseline hepatic impairment, respectively compared to subjects with normal hepatic function. In another trial, the pharmacokinetics of abiraterone were examined in subjects with baseline severe (N=8) hepatic impairment (Child-Pugh Class C) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone increased by approximately 7-fold and the fraction of free drug increased 2-fold in subjects with severe baseline hepatic impairment compared to subjects with normal hepatic function. No dosage adjustment is necessary for patients with baseline mild hepatic impairment. In patients with baseline moderate hepatic impairment (ChildPugh Class B), reduce the recommended dose of ZYTIGA to 250 mg once daily. Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C). If elevations in ALT or AST >5X ULN or total bilirubin >3X ULN occur in patients with baseline moderate hepatic impairment, discontinue ZYTIGA treatment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

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Cancer Care

The State of Side-Effect Management... Continued from the cover out proper guidance, these side effects can also lead to emergency department visits and affect treatment adherence and completion. Each patient with cancer responds differently to treatment, and in the past few years, researchers and providers have discovered better ways to predict, reduce, and even prevent certain side effects, leading, in some cases, to more tolerable treatments and better adherence. Controlling side effects and managing comorbid conditions and risks should be part of every patient’s cancer care program. Clinical, physical, functional, cognitive, and psychosocial assessments, along with education and self-care, are also cornerstones to better care and can be improved when providers and care teams take the following steps: • Devote more time to patients and their families before treatment selection • Improve patient education and teaching via conversations between the patient and a provider, care coach, or navigator to explain the risks and benefits of each treatment option • Complete a thorough medical history and physical examination, and use functional or comorbid tools (eg, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index) • Strengthen patient–doctor communications regarding life-altering side effects. Patient education regarding treatment options and potential risks, benefits, and side effects is essential and should be prioritized in every oncology practice and cancer clinic. As oncologists and oncology nurses, we have an ethical responsibility to teach and reinforce the proactive management of side effects, but currently we are falling short in this area. Too many patients who should

be managed by their physicians and nurses are being hospitalized for side effects and adverse drug reactions. Clinical and financial data analyses show that patients who are diagnosed with late-stage cancers, those

Sheryl A. Riley, RN, OCN, CMCN

Controlling side effects and managing comorbid conditions and risks should be part of every patient’s cancer care program. diagnosed with cancer at higher acuity levels, and those who are receiving cancer treatments are hospitalized at a higher rate than those with early-stage disease.

High Costs In 2012, the Healthcare Cost and Utilization Project examined adult cancer hospitalizations using data collected in 2009 from its Nation al Inpatient Sample. The review showed that approximately 4.7 million hospitalizations of adult patients were cancer-related; in 1.2 million (25%) of these hospitalizations, cancer was the principal diagnosis.1 This came at a cost of $20.1 billion in inpatient hospital costs. Patients who incurred the highest

Oncology Practice Management

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daily costs were patients with prostate ($4600), breast ($4100), and thyroid ($3500) cancers. Furthermore, the most common cancer hospitalizations among men were for prostate cancer, secondary malignancies or metastatic cancer, and lung cancer; hospitalizations related to kidney cancer in adult men increased 40% from 2000 to 2009.1 The most common cancer hospitalizations among women were for secondary malignancies as well as for breast and lung cancers. Bronchus, lung, and colon cancers, as well as secondary malignancies, accounted for more than one-third of the total cost of hospital stays for cancer. In a separate report, investigators with the Healthcare Cost and Utilization Project assessed hospital readmissions in 2009 for cancer surgery in teaching versus nonteaching hospitals in New York. Thirty-day readmissions were assessed from 21,945 admissions for cancer surgery, and the overall readmission rate was 9.3%, with 11.2% of readmissions occurring in nonteaching hospitals, and 8.6% occurring in teaching hospitals.2 Factors that increased the risk for 30-day readmission for a preventable cause among patients with cancer were male sex, undergoing surgery at a nonteaching hospi-

By the Numbers Close to 4.7 million hospitalizations in 2009 were cancer-related Inpatient hospitalizations for cancer diagnoses in 2009 cost

$20.1 billion

More than half of unplanned hospitalizations of patients with cancer occur within 1 year after diagnosis

Cancer Care

tal, African American race, and certain comorbidities. Little changed in the years that followed. A review of the University HealthSystem Consortium database from 2010 to 2013 by Brown and colleagues demonstrated that Medicare-estimated readmission costs were $17 billion annually, and investigators showed that more than 50% of patients who were discharged after surgery died or were rehospital-

gastrointestinal cancer aged ≥66 years. The rate of unplanned hospitalizations was 58.1%, and 55.9% of these hospitalizations occurred within the first year of cancer diagnosis. Moreover, the top reasons for unplanned hospitalizations—fluid and electrolyte disorders, intestinal obstruction, pneumonia, congestive heart failure, chronic obstructive pulmonary disease, and bronchiectasis—were considered potentially pre-

mon adverse drug reaction, and drug combinations, including antihypertensives and long-term corticosteroids, increased the risk of potential drug–drug interactions. The key points in most studies were that many of the unplanned hospitalizations that were reported were potentially preventable and were related to patients’ high comorbidity scores. This means that oncologists do not have a clear picture of their patients—or their patients’ expectations—before or while making decisions about the The rate of unplanned hospitalizations was 58.1%, most appropriate cancer treatment. and 55.9% of these hospitalizations occurred Completing full clinical histories within the first year of cancer diagnosis. Moreover, and examinations, as well as cognitive, functional, and psychosocial the top reasons for unplanned hospitalizations assessments should not be overwere considered potentially preventable. looked or taken for granted. Too often, pretesting and full clinical assessments of patients’ histories ized <1 year after discharge.3 The ventable, and lead author Joanna- and care expectations are oversame review found that patients Grace M. Manzano, MD, noted that looked or not revisited once treatwith cancer receiving medical ser- these comorbidities “may help iden- ment is initiated. vices were readmitted more than tify areas of focus for improvement or Treating physicians (ie, oncolopatients with cancer receiving surgi- intervention.” Further analysis re- gists, primary care physicians, and cal services, and noted that Nation- vealed that patients with esophageal, other specialists) should recognize al Cancer Institute–designated com- gastric, pancreatic, and rectal can- that elderly patients who have gasprehensive cancer centers had a cers, as well as patients with regional higher readmission rate than non- and distant diseases, were at higher KEY POINTS designated cancer centers. risk for unplanned hospitalizations. n Controlling side effects Overall, almost one-third of paAnother prospective study that should be part of every tients were readmitted to hospitals examined drug-related problems and patient’s cancer care program ≤7 days after discharge; 33% of these their correlation with unplanned n Patient education regarding readmissions were the result of po- hospitalizations focused on 2 oncoltreatment options as well as tentially preventable side effects (eg, ogy units with patients diagnosed potential risks, benefits, and nausea, vomiting, dehydration, and with solid tumors or lymphoma.5 side effects is essential Results were described as predictpostoperative pain). n Many of the top reasons for able; the incidence of unplanned unplanned hospitalizations of Unplanned Hospitalizations hospitalizations associated with patients with cancer, such as A study published in October drug-related problems was 12.4%, fluid and electrolyte disorders 2014 showed that unplanned hospi- approximately half of which were and intestinal obstruction, talization rates among patients with potentially preventable events. The are potentially preventable gastrointestinal cancers are higher study revealed that the majority of n Proactive education and than unplanned hospitalizations re- the admissions related to drug-relatemotional support for lated to some other cancers, but, ed problems were adverse drug reacpatients and their families most importantly, they are also po- tions that were moderately severe as well as frequent followtentially preventable.4 The study (N = 155; 94.5%), or probably/defiups and comprehensive used the Texas Cancer Registry and nitely preventable (N = 86; 52.4%). monitoring can help keep Medicare claims data for in-hospital It is also important to note that feside effects under control admissions from 30,199 patients with brile neutropenia was the most comContinued on page 22

June 2015

www.OncPracticeManagement.com

Cancer Care

The State of Side-Effect Management... Continued from page 21 trointestinal cancer are vulnerable to unplanned hospitalizations. Knowing that elderly patients with gastrointestinal cancer are prone to more frequent unplanned hospitalizations, healthcare providers should promote efforts to improve the coordination of care among everyone involved in caring for them. Patients would likely benefit from continued, close follow-up with their oncologists, oncology care managers, or even their primary care physicians during treatment and for years to come. All of this research and information affirms that the burden of readmissions and unplanned hospitalizations caused by side effects and poor symptom management falls on the shoulders of the patients, their families, and ancillary care systems, when it should be the responsibility of the treating physicians and their clinical teams. Improving side-effect manage-

ment for patients is a goal for which every oncology clinic and practice should strive. Proactive side-effect

Improving side-effect management for patients is a goal for which every oncology clinic and practice should strive.

cal assessment tools to better understand the patient’s comorbid history, physical health, cognitive function, mental and emotional health, as well as care expectations should be a key part of every oncology practice. Readmissions and unplanned hospitalizations play a role in decreasing a patient’s survival, and oncology care teams must improve side-effect management to prevent this. l

References

education and emotional support for patients and their families, as well as frequent, comprehensive follow-ups and monitoring before, during, and after treatment are essential. These steps can go a long way in keeping patients’ side effects under control and decreasing unplanned hospitalizations. In addition, the use of clini-

1. Price RA, Stranges E, Elixhauser A. Cancer hospitalizations for adults, 2009. www.hcup-us.ahrq.gov/reports/ statbriefs/sb125.pdf. Published February 2012. Accessed June 8, 2015. 2. Kuznar W. Causes of hospital readmissions of patients with cancer. Am Health Drug Benefits. 2013;6:22-23. 3. Brown EG, Burgess D, Li C, et al. Hospital readmissions: necessary evil or preventable target for quality improvement. Ann Surg. 2014;260:583-591. 4. Manzano JG, Luo R, Elting LS, et al. Patterns and predictors of unplanned hospitalization in a population-based cohort of elderly patients with GI cancer. J Clin Oncol. 2014;32:3527-3533. 5. Chan A, Soh D, Ko Y, et al. Characteristics of unplanned hospital admissions due to drug-related problems in cancer patients. Support Care Cancer. 2014;22: 1875-1881.

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Medicare Reimbursement

US Oncologists Favor Establishment of NICE-Like Body to Determine Medicare Reimbursement By Rosemary Frei, MSc

ccording to a recent study, 63.6% of oncologists surveyed favor the establishment of an independent panel of health experts to decide which treatments Medicare will pay for based on a cost-benefit analysis (Gogineni K, et al. J Clin Oncol. 2015;33:846-853). Less than 50% of patients and members of the general public think this is a good idea. The United Kingdom’s National Institute for Health and Care Excellence (NICE) is one model for such a panel. Despite oncologists’ support, “I think the culture in the US is such that the fear of fewer choices (even if we can safely say that more choices does not necessarily mean better care) will make it very difficult to

In addition, “having clinical guidelines that have to be met, especially in oncology, in order to get reimbursed would be one way to ensure that high-quality care is being delivered,” Dr Gogineni added.

Study Details A total of 326 patients with cancer with appointments at the University of Pennsylvania’s Abramson Cancer Center, as well as 250 oncologists and hematologists and 891 members of the general public completed the survey. The majority of the respondents said they feel Medicare spending is a moderate or “big” problem facing the United States, and that cuts can be made without denying health-

Despite oncologists’ support, “the culture in the US is such that the fear of fewer choices…will make it very difficult to institute a body like NICE.” —Keerthi Gogineni, MD, MSHP

institute a body like NICE,” lead investigator Keerthi Gogineni, MD, MSHP, Assistant Professor of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, told Value-Based Cancer Care. “I would hope that one way around this would be to require new drug/ technology applications to include an incremental cost-effectiveness analysis as part of the approval process, so that at least we begin generating the data we need to be able to delineate what has value,” she said.

care to anyone who really needs it. Furthermore, in response to a menu of 6 potential factors that increase Medicare spending, drug company pricing and insurance company profits were rated as the top 2 contributors to the problem. Physicians and hospitals also share the blame, however, according to survey respondents—70.3% of oncologists thought unnecessary tests and treatments add a moderate or a large amount to Medicare costs, as did 69.1% of patients with cancer and 80.9% of the general public respondents.

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In addition, 66.9% of patients with cancer and 79.4% of the public responded in the affirmative that hospitals or doctors committing “fraud by submitting bills for services not provided” contributes significantly to high Medicare costs. Only 19.2% of oncologists thought this to be true. The multivariable analysis revealed that African Americans, Hispanic Americans, and Americans aged ≥55 years were most likely to believe that provider fraud contributes to high Medicare costs.

Oncologists Concern with High Cost of Patient Care The researchers suggested that these results indicate that “health care providers are no longer impervious to criticism as a major contributor of high costs.” This corroborates “physicians’ apprehension about Centers for Medicare and Medicaid Services’ disclosure of provider utilization and payment data,” they wrote. The survey also included 4 proposed solutions to high Medicare costs. In response to the first solution, “Refuse to pay when a less expensive test or treatment has been shown to work just as well”—more than 75% of patients, oncologists, and the public supported that proposal. Means testing, in which patients with more financial resources pay a larger portion of their costs, was supported by small majorities of the 3 groups. Means testing was most highly favored by members of the public who were male or Democrats. Creating an annual ceiling for the amount that Medicare would spend on any 1 person was far less popular, garnering only 12.9% of patients’ support, 16.8% of oncologists’, and 28.3% of the general public’s. l

Patient Support

Future of Patient Support Services Offers Challenges, Opportunities By Rosemary Frei, MSc

hree of the main factors currently influencing patient support services are population health management, patient engagement, and shifting perspectives in biopharma, Tracy Foster told a roomful of attendees recently at the 2015 Patient Assistance & Access Programs meeting held in Baltimore, MD. In her presentation, Ms Foster, President of Lash Group and Premier Source, a part of AmerisourceBergen, walked participants through these key factors and how stakeholders within the healthcare system, from patients to manufacturers, play an important role. She also recently spoke with Oncology Practice Management regarding the topics that were part of her keynote address. “Some of the key trends in the industry—the growth of population health management, trying to curb costs and improve quality—are really requiring providers to develop new capabilities related to coordinating care and referral management,” Ms Foster said. “For oncologists, it’s continuity of care with primary care providers and other specialists, and a key to that is patient adherence and engagement. We see that as a win-winwin-win with providers, patients, insurers, and manufacturers: adherence

“The patient support program has to address the patients’ needs as they work across the program, starting in the inpatient setting to transitioning to the outpatient setting.” —Tracy Foster

and engagement is a critical success factor for all of those constituents.” Population health management is a solidly established trend, with providers, government, and private payers intensifying their focus on value-based payment, Ms Foster said. Medicare shared savings programs

KEY POINTS n Providers, government, and private payers are intensifying their focus on value-based payment n Maximizing patient adherence and engagement is widely recognized as being essential to optimizing healthcare n The success of patient support programs involves a patient-centered approach throughout the patient journey n In order to improve adherence, it is essential to think about the patient holistically.

(SSPs), a major driver in population health management, remain rooted in fee-for-service reimbursement, she noted, and have not produced the level of value share among participating accountable care organizations (ACOs) that is needed to drive confirmed growth of this model. The program is being adapted, however, and ACOs are continuing to focus their business models on integrating high-quality, low-cost providers and establishing streamlined care pathways. This focus requires improved data sharing between all healthcare partners, Ms Foster said. It also involves coordinated care transitions, the alignment of quality targets, and leveraging worksite wellness programs to supplement patient support programs. “[This means that] patient support programs are really going to need to be positioned in a way that they work in these coordinated-care networks,” Ms Foster said. “Patients receiving a certain product will not only be seen by their oncologist, they’ll also be seen by their primary care provider. So the patient support program has to address the patients’ needs as they work across the program, starting in the inpatient setting to transitioning to the outpatient setting.” Within population health management, there also is the challenging element of gathering all patient-related quality metrics required by the Medicare SSP, said Ms Foster. As manufacturers are thinking about patient support programs, she suggested that they question whether the programs are designed to help and complement an oncologist’s tracking of quality, or if they add to the complexity.

Continued on page 28

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Patient Support

Future of Patient Support Services Offers... Continued from page 26 Figure Patient Risk Stratification Pyramid n

Em pow erm ent

Activated

Disconnected

Disengaged

Reprinted with permission from Lash Group, a part of AmerisourceBergen.

Maximizing patient adherence and engagement is also widely recognized as being essential to optimizing healthcare. She cited in her presentation a survey of pharmacy and medical directors conducted by Xcenda, a part of AmerisourceBergen, which was originally fielded in April 2011 and then repeated in May 2013, with 59 and 60 respondents, respectively. The majority of respondents indicated they are willing to work with pharmaceutical companies to provide services to high-risk patients and, in return, to report on and improve the patients’ compliance and adherence. A total of 7% of the 2011 survey respondents and 17% of the 2013 respondents indicated a willingness to consider a pharmaceutical company’s oncology product for their formulary if the manufacturer also offered an adherence program. Ensuring ongoing success of patient support programs also involves

a patient-centric approach throughout the patient journey, noted Ms Foster. For example, a patient using an oral oncolytic starts with an initial visit to his or her primary care provider, where the path to diagno sis starts and where personalized health-coaching interactions can be used to optimize patient engagement. Similarly, said Ms Foster, through diagnosis, treatment, and aftercare, there are many points at which the patient’s team can work to coordinate care such that they understand his or her experience, maximize engagement, empower the patient, and work with him or her to achieve optimal care planning, clinical support, adherence, compliance, and, ultimately, treatment efficacy.

the opportunity is to ensure that their offerings address the full patient experience from diagnosis onward, with more patient engagement, so the patient is really a part of the program.” To this end, pharmaceutical companies have shifted perspectives and developed ways to segment patients based on their risk of noncompliance (Figure). Patients can then be provided services based on where they are along the adherence risk spectrum, said Ms Foster. More and more of these services are being delivered via patients’ smartphones. This includes everything from enrollment of patients in patient support programs online or via an electronic medical record to text or e-mail alerts about the next clinic appointment. How-

“There is always going to be a need to troubleshoot a patient issue, and providers want a professional, knowledgeable, high-quality customer service experience when they need to connect in a live, direct fashion.” Adherence is the linchpin for much of this work, and in order to make a difference in this area, it is essential to take a broader approach and think about the patient more holistically, Ms Foster said. One of the key challenges—which is also an opportunity—is to unite adherence strategies with other efforts to engage patients, she said. “In the past, manufacturers have partnered with oncology practices to provide patient support programs that were educationally oriented, a ‘one-size-fits-all’ approach to the patient,” Ms Foster said. “And really

ever, patients and physicians will still expect some high-touch communication, she added. “There is always going to be a need to troubleshoot a patient issue, and providers want a professional, knowledgeable, high-quality customer service experience when they need to connect in a live, direct fashion,” said Ms Foster. “That’s why manufacturers are investing in higher-quality customer service models, which means hiring oncology-certified nurses and former practice managers to support patients in their call centers and working with patients’ adherence.” l

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Oncology Practice Management

I June 2015

Human Resources

Men and Women in the Workforce: What Has Changed? By Ruth Linné Lander, FACMPE

ecently retired and looking back over my decades in the workforce, I see gender issues once again gaining strength. I was raised to believe there were no gender barriers or limitations, and most of what I have seen in my youth and working years has supported that. Yet significant events stand in stark contrast, leaving an indelible mark in my mind and a subtle reminder of a different era. I recall as an adolescent wanting to play baseball or do woodworking in school in New York City, but being required to take cooking and sewing classes. I remember a wonderful teacher in junior high school who struggled to fit into regular work clothes; it seemed obvious that she was pregnant. When I asked my homeroom teacher why she was wearing such tight clothing, she told me the teacher needed to keep working and could not if maternity clothes became needed. In these earlier years, many laws like the Equal Pay Act of 1963 or Title VII of the Civil Rights Act of 1964 barring employment discrimination had not yet been enacted or had been enacted but were not highly enforced. By the time I started working fulltime in the late 1960s, women were just entering the workforce in greater numbers. The women’s liberation movement was picking up steam, yet problems still existed. During those years, I recall a young coworker who was terminated from her clerical position at an insurance agency when she reached 6 months in her pregnancy. Needing the income, she begged the manager to let her keep working, but the manager terminated her anyway. Years later, as a new employee of an insurance agency, I broached the idea

of equal pay for equal work with the owner. I was told that my male counterpart with the same job had a family to support so he had to make more money than I was being paid, even though at that time I was the main supporter for my husband and myself. As my work experience increased, I could see the working world for women was not what I had expected growing up. In fact, I learned that gender, not competence, seemed to be what mattered most.

the hands-on life experiences with the move toward gender equity and nondiscrimination. As a result, their attention to their own perspectives on gender equity may be less developed, and this leaves us vulnerable to repeating history. Women bring a wealth of knowledge, skill, and talent to the workforce today. Their complementary style of interacting with information and colleagues adds a richness to organizations across the globe. I have observed, though, that some men are less comfortable with these differences, and I have seen women marginalized or discounted in a company when they bring a relational or passionate element to a discussion. In addition, women tend to be delegated to an outsider role. Often they are left out of discussions about topics such as sports, cars, or fishing that their male counterparts so easily fall into. They also tend to be excluded from gatherings after work at the local watering hole, or from the days spent on the golf course. This subtle but continued exclusion of women in the social aspect of the workplace gives them a serious disadvantage when it comes time to weighing in on decisions or applying for a promotion. My professional acquaintances and friends privately confirm this reality but will not share it in writing. I recently went happily into retirement after nearly 50 years of full-time work. As I parted, I felt some sadness that things are the way they are today in the workforce, but I also left with hope that the future will be better than the past…or the present. l

I could see the working world for women was not what I had expected growing up. In fact, I learned that gender, not competence, seemed to be what mattered most. I have been a member of the workforce for nearly 5 decades, and based on my current observations gleaned from engaging with multiple medical groups and organizations throughout the United States, it seems, unfortunately, that this reality persists even today. Working men in these organizations who experienced the women’s revolution of the 1960s and 1970s have seen injustices such as pay inequities and discrimination against pregnant workers rectified by law. Today they seem to have either a healthy respect for gender equality or a healthy appreciation of what women can bring to the workplace at all levels. I have observed, however, that men who did not experience this revolution firsthand are in a different place. This population seems to lack

June 2015

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Your Patients, Your Practice… Helping Your Practice This comprehensive financial assistance program offers ongoing support across the reimbursement spectrum to help you help your patients. Complete Provider Assistance Benefits verification Prior authorization tracking Regionally dedicated case managers Local access and reimbursement specialists Denied claims assistance Indication XTANDI (enzalutamide) capsules is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Important Safety Information Contraindications XTANDI (enzalutamide) capsules can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant. Warnings and Precautions In Study 1, conducted in patients with metastatic castration-resistant prostate cancer (CRPC) who previously received docetaxel, seizure occurred in 0.9% of patients who were treated with XTANDI and 0% treated with placebo. In Study 2, conducted in patients with chemotherapy-naïve metastatic CRPC, seizure occurred in 0.1% of patients who were treated with XTANDI and 0.1% treated with placebo. Patients experiencing a seizure were permanently discontinued from therapy and all seizure events resolved. There is no clinical trial experience re-administering XTANDI to patients who experienced a seizure, and limited clinical trial experience in patients with predisposing factors for seizure. Study 1 excluded the use of concomitant medications that may lower threshold, whereas Study 2 permitted the use of these medications.

Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity during which sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment. Adverse Reactions The most common adverse reactions (≥ 10%) reported from the two combined clinical trials that occurred more commonly (≥ 2% over placebo) in the XTANDI-treated patients were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/ vertigo. Other Adverse Reactions include: • Laboratory Abnormalities: In the two studies, Grade 1-4 neutropenia occurred in 15% of patients treated with XTANDI (1% Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade 3-4). The incidence of Grade 1-4 thrombocytopenia was 6% of patients treated with XTANDI (0.3% Grade 3-4) and 5% of patients on placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of patients treated with XTANDI (0.2% Grade 3-4) and 16% of patients treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients treated with XTANDI

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(0.1% Grade 3-4) and 2% of patients treated with placebo (no Grade 3-4). • Infections: In Study 1, 1% of XTANDI versus 0.3% of placebo patients and in Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death. • Falls: In the two studies, falls including fall-related injuries occurred in 9% of XTANDI patients vs 4% treated with placebo. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients and included non-pathologic fractures, joint injuries, and hematomas. • Hypertension: In the two studies, hypertension was reported in 11% of patients receiving XTANDI and 4% of patients receiving placebo. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of XTANDI or placebo treated patients. Drug Interactions • Effect of Other Drugs on XTANDI – Administration of strong CYP2C8 inhibitors can increase the plasma exposure to XTANDI. Co-administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If co-administration of XTANDI cannot be avoided,

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reduce the dose of XTANDI. Co-administration of XTANDI with strong or moderate CYP3A4 and CYP2C8 inducers may alter the plasma exposure of XTANDI and should be avoided if possible. • Effect of XTANDI on Other Drugs – XTANDI is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. Avoid CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring. PLEASE SEE BRIEF SUMMARY OF COMPLETE PRESCRIBING INFORMATION ON FOLLOWING PAGES.

XTANDI Support SolutionsSM, a component of Astellas Access ServicesSM 1-855-8XTANDI (1-855-898-2634); Fax 1-855-982-6341; XTANDISupportSolutions.com ©2014 Astellas Pharma US, Inc. All rights reserved. 076-0329-PM 9/14 Printed in USA XTANDI, Astellas, and the flying star logo are trademarks of Astellas Pharma, Inc.

XTANDI® (enzalutamide) capsules for oral use Initial U.S. Approval: 2012 BRIEF SUMMARY OF PRESCRIBING INFORMATION The following is a brief summary. Please see the package insert for full prescribing information. INDICATIONS AND USAGE

Grade 3 and higher adverse reactions were reported among 47% of XTANDI-treated patients and 53% of placebo-treated patients. Discontinuations due to adverse events were reported for 16% of XTANDI-treated patients and 18% of placebo-treated patients. The most common adverse reaction leading to treatment discontinuation was seizure, which occurred in 0.9% of the XTANDI-treated patients compared to none (0%) of the placebo-treated patients. Table 1 shows adverse reactions reported in Study 1 that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm.

Table 1. Adverse Reactions in Study 1 (cont.) Respiratory Disorders

Table 1. Adverse Reactions in Study 1

Study 2: Chemotherapy-naive Metastatic CastrationResistant Prostate Cancer Study 2 enrolled 1717 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy, of whom 1715 received at least one dose of study drug. The median duration of treatment was 17.5 months with XTANDI and 4.6 months with placebo. Grade 3-4 adverse reactions were reported in 44% of XTANDItreated patients and 37% of placebo-treated patients. Discontinuations due to adverse events were reported for 6% of XTANDI-treated patients and 6% of placebo-treated patients. The most common adverse reaction leading to treatment discontinuation was fatigue/asthenia, which occurred in 1% of patients on each treatment arm. Table 2 includes adverse reactions reported in Study 2 that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm.

XTANDI N = 800

XTANDI is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Grade 1-4a (%)

CONTRAINDICATIONS Pregnancy XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss [see Use in Specific Populations (8.1)]. WARNINGS AND PRECAUTIONS Seizure In Study 1, which enrolled patients who previously received docetaxel, 7 of 800 (0.9%) patients treated with XTANDI experienced a seizure and no patients treated with placebo experienced a seizure. Seizure occurred from 31 to 603 days after initiation of XTANDI. In Study 2, 1 of 871 (0.1%) chemotherapy-naive patients treated with XTANDI and 1 of 844 (0.1%) patients treated with placebo experienced a seizure. Patients experiencing seizure were permanently discontinued from therapy and all seizure events resolved. There is no clinical trial experience readministering XTANDI to patients who experienced seizure. Limited safety data are available in patients with predisposing factors for seizure because these patients were generally excluded from the trials. These exclusion criteria included a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation. Study 1 excluded the use of concomitant medications that may lower the seizure threshold, whereas Study 2 permitted the use of these medications. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment. ADVERSE REACTIONS Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Two randomized clinical trials enrolled patients with metastatic prostate cancer that has progressed on androgen deprivation therapy (GnRH therapy or bilateral orchiectomy), a disease setting that is also defined as metastatic CRPC. In both studies, patients received XTANDI 160 mg orally once daily in the active treatment arm or placebo in the control arm. All patients continued androgen deprivation therapy. Patients were allowed, but not required, to take glucocorticoids. The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the XTANDI-treated patients from the two randomized clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo. Study 1: Metastatic Castration-Resistant Prostate Cancer Following Chemotherapy Study 1 enrolled 1199 patients with metastatic CRPC who had previously received docetaxel. The median duration of treatment was 8.3 months with XTANDI and 3.0 months with placebo. During the trial, 48% of patients on the XTANDI arm and 46% of patients on the placebo arm received glucocorticoids.

General Disorders Asthenic Conditionsb Peripheral Edema

Placebo N = 399

Grade Grade Grade 3-4 1-4 3-4 (%) (%) (%)

50.6

9.0

44.4

9.3

15.4

1.0

13.3

0.8

Musculoskeletal And Connective Tissue Disorders Back Pain

26.4

5.3

24.3

4.0

Arthralgia 20.5 Musculoskeletal 15.0 Pain Muscular 9.8 Weakness Musculoskeletal 2.6 Stiffness Gastrointestinal Disorders

2.5

17.3

1.8

1.3

11.5

0.3

1.5

6.8

1.8

0.3

0.0

21.8

1.1

17.5

0.3

Hot Flush

20.3

0.0

10.3

0.0

Hypertension

6.4

2.1

2.8

1.3

Diarrhea Vascular Disorders

Nervous System Disorders Headache

12.1

0.9

5.5

0.0

Dizzinessc Spinal Cord Compression and Cauda Equina Syndrome Paresthesia Mental Impairment Disordersd Hypoesthesia

9.5

0.5

7.5

0.5

7.4

6.6

4.5

3.8

Epistaxis

3.3

0.1

1.3

0.3

a CTCAE v4 b Includes asthenia and fatigue. c Includes dizziness and vertigo. d Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention. e Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis. f Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

Table 2. Adverse Reactions in Study 2 XTANDI N = 871 Grade 1-4a (%)

Grade 3-4 (%)

Placebo N = 844 Grade 1-4 (%)

Grade 3-4 (%)

General Disorders Asthenic 46.9 3.4 33.0 2.8 Conditionsb Peripheral 11.5 0.2 8.2 0.4 Edema Musculoskeletal And Connective Tissue Disorders Back Pain

28.6

2.5

22.4

3.0

Arthralgia

21.4

1.6

16.1

1.1

Gastrointestinal Disorders

6.6

0.0

4.5

0.0

4.3

0.3

1.8

0.0

4.0

Infections And Infestations Upper Respiratory Tract 10.9 Infectione Lower Respiratory 8.5 Tract And Lung f Infection Psychiatric Disorders

0.3

0.0

1.8

6.5

0.0

0.3

2.4

4.8

1.3

Insomnia

8.8

0.0

6.0

0.5

Anxiety

6.5

0.3

4.0

0.0

Renal And Urinary Disorders Hematuria

6.9

1.8

4.5

1.0

Pollakiuria

4.8

0.0

2.5

0.0

Injury, Poisoning And Procedural Complications Fall 4.6 0.3 1.3 Non-pathologic 4.0 1.4 0.8 Fractures Skin And Subcutaneous Tissue Disorders

0.0 0.3

Pruritus

3.8

0.0

1.3

0.0

Dry Skin

3.5

0.0

1.3

0.0

Constipation

23.2

0.7

17.3

0.4

Diarrhea

16.8

0.3

14.3

0.4

Vascular Disorders Hot Flush

18.0

0.1

7.8

0.0

Hypertension

14.2

7.2

4.1

2.3

Nervous System Disorders Dizzinessc

11.3

0.3

7.1

0.0

Headache

11.0

0.2

7.0

0.4

Dysgeusia

7.6

0.1

3.7

0.0

5.7

0.0

1.3

0.1

2.1

0.1

0.4

0.0

0.6

8.5

0.6

0.0

10.5

0.0

1.5

4.7

1.1

0.1

5.7

0.0

Mental Impairment Disordersd Restless Legs Syndrome

Respiratory Disorders Dyspneae

11.0

Infections And Infestations Upper Respiratory 16.4 Tract Infectionf Lower Respiratory Tract And 7.9 Lung Infectiong Psychiatric Disorders Insomnia

8.2

Table 2. Adverse Reactions in Study 2 (cont.) Renal And Urinary Disorders Hematuria

8.8

1.3

5.8

1.3

Injury, Poisoning And Procedural Complications Fall

12.7

1.6

NonPathological 8.8 2.1 Fracture Metabolism and Nutrition Disorders Decreased 18.9 0.3 Appetite

5.3

0.7

3.0

1.1

16.4

0.7

8.5

0.2

Investigations Weight Decreased

12.4

0.8

Reproductive System and Breast Disorders Gynecomastia

3.4

0.0

1.4

0.0

a b c d

CTCAE v4 Includes asthenia and fatigue. Includes dizziness and vertigo. Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention. e Includes dyspnea, exertional dyspnea, and dyspnea at rest. f Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis. g Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

Laboratory Abnormalities In the two randomized clinical trials, Grade 1-4 neutropenia occurred in 15% of patients treated with XTANDI (1% Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade 3-4). The incidence of Grade 1-4 thrombocytopenia was 6% of patients treated with XTANDI (0.3% Grade 3-4) and 5% of patients treated with placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of patients treated with XTANDI (0.2% Grade 3-4) and 16% of patients treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients treated with XTANDI (0.1% Grade 3-4) and 2% of patients treated with placebo (no Grade 3-4). Infections In Study 1, 1% of patients treated with XTANDI compared to 0.3% of patients treated with placebo died from infections or sepsis. In Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death. Falls and Fall-related Injuries In the two randomized clinical trials, falls including fall-related injuries, occurred in 9% of patients treated with XTANDI compared to 4% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in patients treated with XTANDI and included non-pathologic fractures, joint injuries, and hematomas. Hypertension In the two randomized trials, hypertension was reported in 11% of patients receiving XTANDI and 4% of patients receiving placebo. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of patients in each arm. DRUG INTERACTIONS Drugs that Inhibit or Induce CYP2C8 Co-administration of a strong CYP2C8 inhibitor (gemfibrozil) increased the composite area under the plasma concentration-time curve (AUC) of enzalutamide plus N-desmethyl enzalutamide by 2.2-fold in healthy volunteers. Co-administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If co-administration of XTANDI with a strong CYP2C8 inhibitor cannot be avoided, reduce the dose of XTANDI [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. The effects of CYP2C8 inducers on the pharmacokinetics of enzalutamide have not been evaluated in vivo. Co-administration of XTANDI with strong or moderate CYP2C8 inducers (e.g., rifampin) may alter the plasma exposure of XTANDI and should be avoided if possible. Selection of a concomitant medication with no or minimal CYP2C8 induction potential is recommended [see Clinical Pharmacology (12.3)]. Drugs that Inhibit or Induce CYP3A4 Co-administration of a strong CYP3A4 inhibitor (itraconazole) increased the composite AUC of enzalutamide plus N-desmethyl

enzalutamide by 1.3-fold in healthy volunteers [see Clinical Pharmacology (12.3)]. The effects of CYP3A4 inducers on the pharmacokinetics of enzalutamide have not been evaluated in vivo. Co-administration of XTANDI with strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine) may decrease the plasma exposure of XTANDI and should be avoided if possible. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) and St. John’s Wort may also reduce the plasma exposure of XTANDI and should be avoided if possible [see Clinical Pharmacology (12.3)]. Effect of XTANDI on Drug Metabolizing Enzymes Enzalutamide is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. At steady state, XTANDI reduced the plasma exposure to midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate). Concomitant use of XTANDI with narrow therapeutic index drugs that are metabolized by CYP3A4 (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus), CYP2C9 (e.g., phenytoin, warfarin) and CYP2C19 (e.g., S-mephenytoin) should be avoided, as enzalutamide may decrease their exposure. If co-administration with warfarin cannot be avoided, conduct additional INR monitoring [see Clinical Pharmacology (12.3)]. USE IN SPECIFIC POPULATIONS Pregnancy - Pregnancy Category X [see Contraindications (4)]. Risk Summary XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no human data on the use of XTANDI in pregnancy and XTANDI is not indicated for use in women, it is important to know that maternal use of an androgen receptor inhibitor could affect development of the fetus. Enzalutamide caused embryofetal toxicity in mice at exposures that were lower than in patients receiving the recommended dose. XTANDI is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with XTANDI. Animal Data In an embryo-fetal developmental toxicity study in mice, enzalutamide caused developmental toxicity when administered at oral doses of 10 or 30 mg/kg/day throughout the period of organogenesis (gestational days 6-15). Findings included embryo-fetal lethality (increased post-implantation loss and resorptions) and decreased anogenital distance at ≥ 10 mg/kg/day, and cleft palate and absent palatine bone at 30 mg/kg/day. Doses of 30 mg/kg/day caused maternal toxicity. The doses tested in mice (1, 10 and 30 mg/kg/day) resulted in systemic exposures (AUC) approximately 0.04, 0.4 and 1.1 times, respectively, the exposures in patients. Enzalutamide did not cause developmental toxicity in rabbits when administered throughout the period of organogenesis (gestational days 6-18) at dose levels up to 10 mg/kg/day (approximately 0.4 times the exposures in patients based on AUC). Nursing Mothers XTANDI is not indicated for use in women. It is not known if enzalutamide 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 XTANDI, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness of XTANDI in pediatric patients have not been established. Geriatric Use Of 1671 patients who received XTANDI in the two randomized clinical trials, 75% were 65 and over, while 31% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients. Other reported clinical

experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Patients with Renal Impairment A dedicated renal impairment trial for XTANDI has not been conducted. Based on the population pharmacokinetic analysis using data from clinical trials in patients with metastatic CRPC and healthy volunteers, no significant difference in enzalutamide clearance was observed in patients with pre-existing mild to moderate renal impairment (30 mL/min ≤ creatinine clearance [CrCL] ≤ 89 mL/min) compared to patients and volunteers with baseline normal renal function (CrCL ≥ 90 mL/min). No initial dosage adjustment is necessary for patients with mild to moderate renal impairment. Severe renal impairment (CrCL < 30 mL/min) and end-stage renal disease have not been assessed [see Clinical Pharmacology (12.3)]. Patients with Hepatic Impairment A dedicated hepatic impairment trial compared the composite systemic exposure of enzalutamide plus N-desmethyl enzalutamide in volunteers with baseline mild or moderate hepatic impairment (Child-Pugh Class A and B, respectively) versus healthy controls with normal hepatic function. The composite AUC of enzalutamide plus N-desmethyl enzalutamide was similar in volunteers with mild or moderate baseline hepatic impairment compared to volunteers with normal hepatic function. No initial dosage adjustment is necessary for patients with baseline mild or moderate hepatic impairment. Baseline severe hepatic impairment (Child-Pugh Class C) has not been assessed [see Clinical Pharmacology (12.3)]. OVERDOSAGE In the event of an overdose, stop treatment with XTANDI and initiate general supportive measures taking into consideration the half-life of 5.8 days. In a dose escalation study, no seizures were reported at < 240 mg daily, whereas 3 seizures were reported, 1 each at 360 mg, 480 mg, and 600 mg daily. Patients may be at increased risk of seizure following an overdose. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been conducted to evaluate the carcinogenic potential of enzalutamide. Enzalutamide did not induce mutations in the bacterial reverse mutation (Ames) assay and was not genotoxic in either the in vitro mouse lymphoma thymidine kinase (Tk) gene mutation assay or the in vivo mouse micronucleus assay. Based on nonclinical findings in repeat-dose toxicology studies, which were consistent with the pharmacological activity of enzalutamide, male fertility may be impaired by treatment with XTANDI. In a 26-week study in rats, atrophy of the prostate and seminal vesicles was observed at ≥ 30 mg/kg/day (equal to the human exposure based on AUC). In 4-, 13-, and 39-week studies in dogs, hypospermatogenesis and atrophy of the prostate and epididymides were observed at ≥ 4 mg/kg/day (0.3 times the human exposure based on AUC). Manufactured by: Catalent Pharma Solutions, LLC, St. Petersburg, FL 33716 Manufactured for and Distributed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Marketed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Medivation, Inc., San Francisco, CA 94105 Revised: September 2014 14B006-XTA-BRFS Rx Only © 2014 Astellas Pharma US, Inc. XTANDI® is a registered trademark of Astellas Pharma Inc.

076-0472-PM

Wealth Management

Common Deductions Taken by Aggressive Taxpayers By Andrew D. Schwartz, CPA, and Lawrence B. Keller, CFP, CLU, ChFC, RHU, LUTCF

t is a fact of life. The current tax system rewards taxpayers who are aggressive with their deductions. To find out what people are deducting, we undertook an informal survey of many of our colleagues who are certified public accountants. We found that a handful of deductions show up repeatedly on the tax returns of those taxpayers who tend to be very aggressive with their deductions. How aggressive are you with the deductions you claim on your income tax return each year (Box)? Below we discuss some of the more common deductions we have found.

tive or managerial tasks within the home office on an ongoing basis to qualify for this deduction.

Home Office Deduction Two things make claiming the home office deduction very attractive. First, the rules are pretty liberal regarding who is eligible to claim the home office deduction, and if you do not own your home, the rent you pay is not otherwise deductible on your federal tax return.

Temporary Job Assignment Temporary job assignments provide taxpayers with the opportunity to claim a huge tax deduction. As long as the following 3 conditions are met, individuals can deduct all of their travel and living expenses while away from home on a temporary job assignment: (1) the assignment must

Andrew D. Schwartz

Lawrence B. Keller

We found that a handful of deductions show up repeatedly on the tax returns of those taxpayers who tend to be very aggressive with their deductions. How aggressive are you with the deductions you claim on your income tax return? A review of the rules shows that to be eligible for a home office deduction, you must use a portion of your home regularly and exclusively for your trade or business. If your home office is used even one day during the year for any other purpose, no deduction will be allowed. In addition, you must perform either the income-producing activity or your administra-

be for a specific length of time, (2) the assignment must last for a period of â&#x2030;¤1 year, and (3) the taxpayer must continue to be engaged in business activities in the general vicinity of the original home, incur duplicated living expenses, or intend to return to his or her original home after the temporary assignment ends. Just imagine how huge this deduc-

Oncology Practice Management

I June 2015

tion can be. Remember, someone qualified to claim the temporary job assignment deduction can deduct travel to and from the job location plus the total amount spent for lodging for up to a full year plus a daily per diem allowance of up to $71 per day (see below).

Automobile Expenses Claiming the automobile deduction has been a favorite of aggressive taxpayers for years. In 2015, taxpayers are allowed to claim a deduction of $0.575 per business mile driven, which includes the following: (1) travel between 2 different workplaces, (2) travel between a residence and a temporary workplace at which a person works on an irregular or short-term basis of <1 year, and (3) travel to and from job interviews, conferences, and continuing education seminars that qualify as deductible business expenses. Since the only information needed to calculate the automobile deduction is the number of business miles driven, it is not too difficult to see why this is one of the favorite deductions for taxpayers who like to be aggressive with their deductions. Noncash Contributions Individuals who itemize their deductions are allowed to claim a deduction for contributions they make to qualified charitable organizations. The gift can be cash, check, or property. Gifts of property, such as clothing and household items, are known as noncash contributions

Wealth Management

and are deductible based on the fair market value of the donated property as of the date of the gift. To deduct a noncash contribution of up to $5000, the person who made the donation is asked to determine fair market value. Enough said.

Per Diem Rates Each year, you might travel quite a bit in connection with conferences

and seminars, job searches, and/or temporary job assignments. The cost of travel, lodging, and 50% of the cost of meals incurred while away from home (and not reimbursed) in connection with these business trips is generally deductible. You can track the cost of meals and incidentals incurred while away on business in 2 different ways. You can either keep receipts each time

you eat a meal during your business trips, or you can use the per diem rates established by the Internal Revenue Service (IRS). Depending on the city, the per diem rate is up to $71 per day. A list of per diem rates by state can be found in IRS Publication 463, “Travel, Entertainment, Gift, and Car Expenses,” or by using the interactive tool available at the US General Ser-

How Aggressive Are You with Your Tax Deductions? Did you claim a home office deduction last year?

I never use a car in connection with my work (0

Yes, I claimed more than 20% of my residence as a

I could claim some of my mileage as business miles,

home office (+2 points)

Yes, but less than 20% of my residence qualifies as

a home office (+1 point)

I either was not eligible to claim the home office

last year, or I own my home and decided not to claim the home office or to claim the new simplified home office (0 points)

I do not own my home, and I do have a home of-

fice, but I did not want to raise any red flags, so I did not bother claiming the home office deduction (–2 points)

Have you ever deducted for a temporary job assignment? Yes, and the deduction was huge (+2 points) Yes, but I only deducted my travel expenses and did

not deduct for my lodging or my food because the deduction seemed excessive (+1 point)

I never had a temporary job assignment (0 points) I was eligible, but did not want to raise any red flags

(–2 points)

Do you claim an annual deduction for your automobile expenses? Each year, I deduct at least 75% of my car’s mileage

as a business expense (+2 points)

Each year, I keep a very accurate log, and only de-

duct the automobile mileage that I am eligible to claim (+1 point)

points)

but do not want to raise a red flag (–2 points)

Did you claim any noncash contributions last year? Yes, and the deduction I claimed was more than

$500 (+2 points)

Yes, but I kept the deduction to less than $500

because I did not want to attach the noncash contributions form (+1 point)

I did not make any noncash contributions last year

(0 points)

No, even though I gave away lots of stuff, I did not

bother to get any receipts and do not want to raise any red flags (–2 points)

Did you do much business travel last year that was not reimbursed? If I get on a plane, it is a business trip, no matter

what (+2 points)

I have no problem deducting my business travel, if

the trip is 100% business (+1 point)

I never have to travel for my job (0 points) I traveled quite a bit and was not always reim-

bursed by my employer, but I did not deduct my business travel because I did not want to raise a red flag (–2 points)

Interpreting your score: ≥5 points, consider yourself aggressive; ≤4 and ≥–4, you are the average taxpayer; ≤–5, consider yourself a timid taxpayer! Continued on page 36

June 2015

www.OncPracticeManagement.com

Wealth Management

Common Deductions Taken by... Continued from page 35 vices Administration website found at www.gsa.gov. Taxpayers who are aggressive with their deductions generally prefer to base their meals and entertainment deduction on the per diem rates, since the only information needed to calculate their deduction is the number of days they were away on business. From what we have seen, these taxpayers seem to find a business purpose for every trip they take.

Summary Just about everyone has friends, family members, or colleagues at work who are very aggressive with the tax deductions they claim. Every year, at about this time, they start

telling you about all of the crazy things they deducted last year. And then they usually try to convince you that what they deducted must be okay, since the IRS never disallowed any of their deductions. Even though the IRS did not question their deductions, however, that should not be interpreted to mean that what they claimed is allowable. It simply means that the IRS did not select this person’s tax return for audit. Remember, everything is deductible until you get audited. l Andrew D. Schwartz, CPA, is a partner in the Boston CPA firm Schwartz & Schwartz, PC, and is also the founder of the MDTAXES Net-

work (www.mdtaxes.com), a national network of certified public accountants who specialize in tax and accounting services for healthcare professionals and their practices. He can be reached with comments or questions by calling 800471-0045 or by sending an e-mail to Andrew@mdtaxes.com. Lawrence B. Keller, CFP, CLU, ChFC, RHU, LUTCF, is the founder of Physician Financial Services, a New York–based firm specializing in income protection and wealth accumulation strategies for physicians. He can be reached with comments or questions by calling 516-677-6211 or by sending an e-mail to Lkeller@physicianfinancial services.com.

CONFERENCE CO-CHAIRS

Sanjiv S. Agarwala, MD

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

Jorge E. Cortes, MD

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

Hope S. Rugo, MD

Professor of Medicine Director, Breast Oncology and Clinical Trials Education UCSF Helen Diller Family Hope Comprehensive S. Rugo, M.D. Cancer Center San of Francisco, Professor MedicineCA Director, Breast Oncology andPMOLive_fi Clinical Trials Education ll042415 University of California San Francisco Helen Diller Fami Cancer Center San Francisco, CA

www.etouches.com/pmolive2015 36

Oncology Practice Management

I June 2015

Hope S. Rugo, MD, is a Professor of Medicine in the Divi the University of California San Francisco, Helen Diller F where she directs Breast Cancer and Clinical Trial Educat novel therapies for advanced breast cancer, immune modu sensitivity, evaluation of circulating cells as novel marker neoadjuvant therapy and supportive care.

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For more information, please visit www.REACHPatientSupport.com or www.nexavar-us.com *Patients who are enrolled in any type of government insurance or reimbursement programs are not eligible. As a condition precedent of the co-payment support provided under this program, e.g., co-pay refunds, participating patients and pharmacies are obligated to inform insurance companies and third-party payors of any benefits they receive and the value of this program, and may not participate if this program is prohibited by or conflicts with their private insurance policy, as required by contract or otherwise. Void where prohibited by law, taxed, or restricted. Patients enrolled in Bayerâ&#x20AC;&#x2122;s Patient Assistance Program are not eligible. Bayer and Onyx may determine eligibility, monitor participation, equitably distribute product and modify or discontinue any aspect of the REACH program at any time, including but not limited to this commercial co-pay assistance program.

Bayer HealthCare Pharmaceuticals Inc., 100 Bayer Boulevard, PO Box 915, Whippany, NJ 07981 USA BAYER, the Bayer Cross, and NEXAVAR are registered trademarks of Bayer. REACH is a service mark of Bayer HealthCare Pharmaceuticals Inc. ÂŠ2015 Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ PP-810-US-1632

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Patient and Provider Access

SGR Is Over: What’s Next for Providers? By Maureen Leddy, JD, Policy Coordinator, Association of Community Cancer Centers

n April 14, 2015, after years of uncertainty and 17 shortterm “doc fix” patches to prevent severe annual cuts to physician reimbursement payments, Congress approved the Medicare Access and CHIP Reauthorization Act (MACRA), bringing an end to the Medicare sustainable growth rate (SGR). This bipartisan, bicameral compromise will provide physicians with the predictability in payments needed to continue to provide high-quality cancer care, while transitioning over a 10-year period to a new Medicare reimbursement system. MACRA establishes a new, dual- track payment system, under which physicians must eventually participate in a merit-based incentive payment system or an alternative payment model system. It extends the Medicare physician reimbursement rate set by last year’s patch to June 2015, after which annual 0.5% increases to payment rates are established through 2019. In 2020, a second 5-year phase begins, during which reimbursement rates remain flat. Before the start of this second phase, providers will need to choose between the merit-based incentive payment system and the alternative payment model system. Providers meeting the criteria for alternative payment model incentives will be excluded from participation in the merit- based system, and payments under the merit-based system will be subject to positive or negative adjustments based on performance. Providers will be evaluated on the following performance criteria: • Quality of care • Resource use • Clinical practice improvement activities

• Use of electronic health records technology. Providers participating in an alternative payment model will instead be eligible for annual lump-sum bo-

This bipartisan, bicameral compromise will provide physicians with the predictability in payments needed to continue to provide high-quality cancer care. nuses equaling 5% of the previous year’s payments upon achieving specified targets in transitioning from a fee-for-service model. In 2026, automatic annual payment rate increases resume, with physicians participating in the merit-based system receiving 0.25% per year increases and those participating in an alternative payment model receiving 0.75% per year increases. MACRA encourages the development of alternative payment models applicable to specialties and small practices, as well as models that align private-based and state-based payers. To this end, MACRA calls for the creation of a Payment Model Tech-

Oncology Practice Management

I June 2015

nical Advisory Committee that will recommend additional alternative payment models to the Centers for Medicare & Medicaid Services (CMS). The Center for Medicare and Medicaid Innovation’s Oncol ogy Care Model initiative already provides a venue for many cancer providers to participate in an alternative payment model. Going forward, the Association of Community Cancer Centers will vigilantly monitor recommendations of the Payment Model Technical Advisory Committee for other alternative payment models that may be relevant to oncology practices. Through 2019, CMS will be going through a regulatory process to further define the merit-based program. We expect to see proposed rules revealed as soon as this summer or fall. There will be multiple rule-making cycles over the next 3 years, and the Association of Community Cancer Centers will monitor this process and provide comments when appropriate. MACRA also provides medical specialty societies and physicians an opportunity to develop and submit to CMS quality measures for the merit-based system that are appropriate to their specialty. Although the details of this submission process are still being determined, we will ensure that the voices of oncology care providers and community cancer centers are heard. MACRA’s intent is not to derail current efforts in moving toward a value-based system, but to amplify them and provide incentives for practices moving in that direction. The Association of Community Cancer Centers looks forward to working with our members to effectively implement the bill and transition toward a new future for physician reimbursement. l

Clinical Trial Tracker

Trials for Patients with Multiple Myeloma

he following clinical trials are currently recruiting patients with multiple myeloma for inclusion in several investigations. Each trial description includes the NLM Identifier to use as a reference with ClinicalTrials.gov.

linical and Molecular C Observational Study This prospective, longitudinal, observational study aims to identify the molecular profiles and clinical characteristics that define subsets of patients with multiple myeloma. Patients who are aged ≥18 years, newly diagnosed with symptomatic multiple myeloma, treatment-naïve but eligible for systemic treatment, and ≤30 days from their baseline bone marrow evaluation may be eligible for this study if other criteria are met. Primary outcome measures for this study are molecular profiles and clinical characteristics at initial diagnosis and relapse, as measured by standard clinical and laboratory assessments. Genomic tests on bone marrow aspirates will be performed at baseline, suspected complete response, and relapse or progression. Secondary outcome measures include rates of survival measured 5 to 8 years from baseline, radiographically assessed bone disease, and health-related quality of life. It is expected this study will enroll 1000 patients at multiple locations throughout the United States. For more information, contact Auclair Daniel at 203-652-0218 or Auclaird@ themmrf.org, or the CoMMpass Contact Center at CoMMpass@ themmrf.org. The NLM Identifier is NCT01454297.

TH-302 plus Dexamethasone This open-label, nonrandomized, parallel-assignment, phase 1/2 study assesses the safety, toler ability, and preliminary efficacy of

TH-302 (a hypoxia-activated pro drug) plus dexamethasone with or without bortezomib in the treatment of patients with relapsed or refractory multiple myeloma. Patients who are aged ≥18 years and whose disease has relapsed or is refractory to ≥2 therapies may be eligible to enroll if other criteria are met. Primary objectives of this study include the determination of safety and tolerability, dose-limiting toxicities, and maximum tolerated dose as well as a recommended phase 2 dosing of TH-302 plus dexamethasone with or without bortezomib in patients with relapsed or refractory multiple myeloma. As part of the study’s secondary objectives, investigators will assess preliminary efficacy of the study drugs as well as progression-free survival. This study is expected to enroll 60 patients at sites throughout the United States. For more information, contact Stephanie Mar at 650-474-8221 or smar@ thresholdpharm.com. The NLM Identifier is NCT01522872.

netic profile, and safety and tolerability of oral CB-5083. Secondary outcome measures include the pharmacokinetic and pharmacodynamic profiles of CB-5083, and the antitumor activity of oral CB-5083 in patients with measurable disease. This study is expected to enroll 50 patients in California, Missouri, New Jersey, and Georgia. For more information, contact Alessandra Cesano, MD, PhD, at 650-443-3019 or acesano@cleavebio.com. The NLM Identifier is NCT02223598.

Osteocytes in Bone Disease Investigators in this exploratory, observational, case-control study hope to compare the serum FGF23, heparanase, Dickkopf1, and plasma klotho levels of patients with relapsed or newly diagnosed multiple myeloma with those of healthy controls. Patients who are aged ≥18 years, are not pregnant, and do not have a history of malignancy in the past 5 years—except for basal-cell and squamous-cell carcinoma of the skin—may be eligible to enroll if other criteria are met. Healthy participants will have their blood drawn, and patients with multiple myeloma will have their blood drawn in addition to bone marrow aspirations. Primary outcome measures are the molecular reactions between osteocytes and multiple myeloma, and secondary outcome measures include correlating FGF23, heparanase, Dickkopf1, and plasma klotho to tumor staging and the extent of bone resorption. This study is expected to enroll 240 patients in Indianapolis, IN. For more information, contact Attaya Suvannasankha, MD, at 317278-9306 or asuvanna@iu.edu. The NLM Identifier is NCT02212262.

B-5083 for Relapsed or C Refractory Multiple Myeloma This nonrandomized, single-group, open-label study seeks to determine the safety, tolerability, dose-limiting toxicities, and maximum tolerated dose of CB-5083 in the treatment of patients with relapsed or refractory multiple myeloma. Patients with an Eastern Cooperative Oncology Group performance status score of ≤2 who are aged ≥18 years and who have adequate organ and cardiac function may be eligible to enroll if other criteria are met. Eligible patients will receive oral CB-5083 as a single agent, and may then receive CB-5083 combined with a low dose of oral dexamethasone if their disease progresses after 2 cycles. Primary outcome measures are the dose-limiting toxicities, pharmacoki-

June 2015

iltuximab for High-Risk S Smoldering Multiple Myeloma This phase 2, randomized,

Continued on page 40

www.OncPracticeManagement.com

Clinical Trial Tracker

Trials for Patients with Multiple... Continued from page 39 double-blind, placebo-controlled study seeks to evaluate the safety and efficacy of siltuximab in the treatment of patients with high-risk smoldering multiple myeloma. Patients who are aged ≥18 years with a diagnosis of smoldering multiple mye loma for <4 years and an Eastern Cooperative Oncology Group performance status score of ≤1 may be eligible to enroll if other criteria are met. Patients will receive either siltuximab or placebo intravenously every 4 weeks until their disease progresses to symptomatic multiple myeloma, toxicity becomes unacceptable, they withdraw their consent, or the end of the study is reached. The primary outcome measure is 1-year progression-free survival, measured from 6 months after randomization of the last patient. Secondary outcome measures include progression-free survival, changes in clinical laboratory values, and overall survival, all of which are assessed 4 years after the last patient is randomized. This study is expected to enroll 74 patients at multiple locations across the United States and abroad. For more information, contact Janssen Research & Development at JNJ.CT@sylogent.com. The NLM Identifier is NCT01484275.

anobinostat for Relapsed and P Relapsed/Refractory Disease This phase 1, open-label study evaluates panobinostat in combination with lenalidomide, bortezomib, and dexamethasone for the treatment of patients with multiple myeloma. Patients who are aged ≥18 years with relapsed or relapsed/ refractory multiple myeloma after receiving ≥2 lines of therapy, and an Eastern Cooperative Oncology Group performance status score of <2 may be eligible to enroll if other criteria are met. Treatment cycles will last 21 days, and participants

will be expected to visit the clinic on days 1, 4, 5, 8, 10, and 11 during the first cycle, and on days 1, 4, 8, and 11 during the second and later cycles. Drugs include oral panobinostat, subcutaneous injections of bortezomib, oral lenalidomide, and oral dexamethasone. Primary outcome measures are the maximum tolerated dose of panobin ostat in combination with lenalidomide, bortezomib, and dexamethasone, and the recommended dose of the combination for future phase 2 studies. Secondary outcome measures are progression-free survival, duration of response, and response to the treatment over a time frame of 2 years. This study is expected to enroll 28 patients in Boston, MA, and Durham, NC. For more information, contact Jacob Laubach, MD, at 617632-4218 or jacobp_laubach@dfci. harvard.edu. The NLM Identifier is NCT01965353.

icolinostat with or without R Bortezomib and Dexamethasone Investigators in this open-label, phase 1/2 study seek to determine the side effects and most effective dose of oral ricolinostat as monotherapy and in combination with bortezomib and dexamethasone (phase 1), as well as the objective response rate of ricolinostat in combination with bortezomib and dexamethasone (phase 2) in the treatment of patients with relapsed or relapsed/refractory multiple myeloma. Patients who are aged ≥18 years with adequate renal and hepatic function and a Karnofsky Performance Status score of ≥70 may be eligible to enroll if other criteria are met. Patients will receive a liquid oral dose of ricolinostat on days 1 to 5 and 8 to 12 of a 21-day treatment cycle. Primary outcome measures are the maximum tolerated dose and objective response rates of ricolinostat

monotherapy and in combination with bortezomib and dexamethasone, and secondary outcome measures include characterizing the safety, determining the single- and multiple-dose pharmacokinetics, and evaluating the pharmacodynamics of ricolinostat with or without bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. For more information, contact Gina Leone at 617-2451300 or gleone@acetylon.com. The NLM Identifier is NCT01323751.

umor-Associated AntigenT Specific Cytotoxic T-Lymphocytes This nonrandomized, open-label study aims to determine the side effects and safest maximum dose of tumor-associated antigen (TAA) specific cytotoxic T-lymphocytes (CTLs), and to determine whether this therapy is effective in the treatment of patients with multiple mye loma. Patients who are aged ≥18 years with a life expectancy of ≥6 weeks and a Karnofsky Performance Status score of ≥50 may be eligible to enroll if other criteria are met. Patients will receive TAA-specific CTLs as therapy for multiple mye loma, or TAA-specific CTLs as adjunctive therapy for patients with multiple myeloma following autologous or syngeneic transplant. The primary outcome measure is the number of patients with adverse events, which will assist in determining the safety of 2 intravenous injections of autologous TAA-specific CTLs in this patient population. Secondary outcome measures include expansion and persistence of the CTLs at 1 year, and reduction of multiple myeloma over a time frame of 8 weeks. This study is expected to enroll 36 patients in Houston, TX. For more information, contact Rammurti Kamble, MD, at 713-441-1450 Continued on page 42

Oncology Practice Management

I June 2015

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

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Clinical Trial Tracker

Trials for Patients with Multiple... Continued from page 40 or RTKamble@houstonmethodist. org. The NLM Identifier is NCT02291848.

icolinostat with R Pomalidomide and Low-Dose Dexamethasone Investigators in this open-label, nonrandomized, phase 1/2 study seek to determine the maximum tolerated dose, safety, and efficacy of ricolino stat in the treatment of patients with relapsed and refractory multiple myeloma. Patients who are aged ≥18 years with measurable levels of myeloma paraprotein in serum (≥0.5 g/ dL), and an Eastern Cooperative Oncology Group performance status score of ≤2 may be eligible to enroll if other criteria are met. Patients will receive ricolinostat in combination with pomalidomide and dexamethasone over a 28-day cycle. Primary outcome measures are the maximum tolerated dose, dosing schedule, and overall response rate of ricolinostat in combination with pomalidomide and low-dose dexamethasone. Secondary outcome measures include safety (assessed by type, frequency, and severity of adverse events, and the relationship of adverse events to the study drug) and efficacy (assessed by time to response, duration of response, time to progression, progression-free survival, and objective response). The study is expected to enroll 100 patients at multiple locations throughout the United States. For more information, contact Gretchen Patrick at 617-245-1319 or gpatrick@acetylon.com. The NLM Identifier is NCT01997840.

CART-19 T-Cells for Multiple Myeloma The purpose of this study is to determine the safety, tolerability, and engraftment potential of chimeric antigen receptor-19 (CART19) T-cells in the treatment of

patients with multiple myeloma who are undergoing salvage autologous stem-cell transplantation (ASCT) following early relapse after their first transplant procedure. Patients who are aged ≥18 years, have undergone previous ASCT for multiple myeloma but have progressed within 365 days of stem-cell infusion, and have an absolute bone marrow plasma cell percentage ≥10% may be eligible to enroll if other criteria are met. Primary outcome measures are the number of adverse events over a 2-year time frame. The study is expected to enroll 15 patients in Philadelphia, PA. For more information, contact Edward Stadtmauer, MD, at 855-216-0098 or PennCancer Trials@emergingmed.com. The NLM Identifier is NCT02135406.

ral LGH447 for Relapsed O and/or Refractory Disease Investigators in this phase 1, open-label, nonrandomized study seek to estimate the maximum tolerated dose and/or recommended dose for expansion of LGH447 as a single agent for once-daily oral administration in the treatment of adult patients with multiple myeloma. Patients who are aged ≥18 years with confirmed diagnoses of multiple myeloma that is relapsed and/or refractory, and an Eastern Cooperative Oncology Group performance status score of ≤2 may be eligible to enroll if other criteria are met. Patients in the first treatment arm will receive oral LGH447 until disease progression or unacceptable toxicity occurs, and patients in the second treatment arm will receive midazolam on 2 separate days—with the first dose administered before the start of LGH447 and the second dose coadministered with LGH447—and continue to receive oral LGH447 until disease progression or unacceptable toxicity occurs. Primary outcome measures are to

Oncology Practice Management

I June 2015

estimate the maximum tolerated dose and/or recommended dose for expansion of LGH447 as a single agent. Secondary outcome measures include antimyeloma activity associated with LGH447, the number of participants with adverse events and serious adverse events, and the pharmacokinetic and pharmacodynamic effects of LGH447. The study is expected to enroll 77 patients at multiple locations throughout the United States and abroad. For more information, contact Novartis Pharmaceuticals at 888-669-6682. The NLM Identifier is NCT01456689.

omalidomide, Marizomib, and P Dexamethasone for Relapsed or Refractory Disease This phase 1, open-label trial seeks to evaluate the 3-drug combination of pomalidomide, marizomib, and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma. Patients who are aged ≥18 years, and who have previously received ≥1 lines of antimyeloma therapy with both lenalidomide and bortezomib—either separately or combined—may be eligible to enroll if other criteria are met. During a 28-day cycle, patients will receive oral pomalidomide on days 1 to 21; intravenous marizomib on days 1, 4, 8, and 11; and oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22, and 23. Primary outcome measures are to determine the maximum tolerated dose and/or the recommended doses for future phase 2 studies of this 3-drug combination. Secondary outcome measures are adverse events and response rates for a time frame of ≤5 years. This study is expected to enroll 36 patients at multiple locations throughout the United States and abroad. For more information, contact Mohit Trikha, PhD, at 858-242-1508 or mohit.trikha@triphaseco.com. The NLM Identifier is NCT02103335. l

Drug Update

Jakafi (Ruxolitinib): First FDA-Approved Medication for the Treatment of Patients with Polycythemia Vera By Lisa A. Raedler, PhD, RPh, Medical Writer

imilar to myelofibrosis and essential thrombocythemia, polycythemia vera is a Philadelphia chromosome–negative myeloproliferative neoplasm.1 Polycythemia vera is characterized by the clonal stem-cell proliferation of red blood cells, white blood cells, and platelets.2,3 Increased red blood cell mass results in the hyperviscosity of the blood, an increased risk for thrombosis, poor quality of life, and a shortened life expectancy.4 Polycythemia vera is a rare condition. The incidence rate of polycythemia vera for all races and ethnicities is higher among men than among women: approximately 2.8 per 100,000 men and approximately 1.3 per 100,000 women.3 Based on several small studies, approximately 22 in 100,000 individuals are affected by polycythemia vera.3 The condition is typically diagnosed in older adults aged 60 to 65 years, and is uncommon in younger people aged <30 years.3 Approximately 96% of patients with polycythemia vera have a mutation of the Janus-associated kinase (JAK) 2 gene.5 In the polycythemia vera progenitor cells, JAK2 is directly involved in the intracellular signaling that occurs after exposure to specific cytokines.5,6 The course of the disease varies.3 Some patients with polycythemia vera have few symptoms, and the condition is discovered only after blood work is performed during a periodic health examination. In others, the signs, symptoms, and compliCopyright © 2015 American Health & Drug Benefits. All rights reserved.

cations result from the high Table 1 Thrombotic Complications in red blood cell count and Polycythemia Vera platelet count.3 In addition, Microvascular complications polycythemia vera evolves to Erythromelalgia postpolycythemia vera mye Headache lofibrosis in up to 10% of paDizziness tients by year 10.7 Visual disturbances Paresthesia Transformation to acute Transient ischemic attack myeloid leukemia has been observed in up to 15% of paMacrovascular complications Arterial thrombotic events tients with polycythemia vera 8 Myocardial infarction after 10 years of the disease. Unstable angina The symptoms of polycyStroke themia vera are primarily rePeripheral arterial occlusion lated to thrombi that result Venous thrombotic events from increased blood viscosity Deep vein thrombosis and high platelet counts. The Pulmonary embolism Intra-abdominal vein thrombosis thrombotic complications are Cerebral vein thrombosis divided into microvascular and macrovascular complicaSources: Michiels JJ, et al. Semin Thromb Hemost. 2006;32:174-207; Falanga A, Marchetti M. tions. The microvascular Hematology Am Soc Hematol Educ Program. complications result from 2012;2012:571-581; Marchioli R, et al. J Clin thrombi in small blood vessels Oncol. 2005;23:2224-2232. and can cause a variety of signs and symptoms, including head- polycythemia vera symptoms, deaches, dizziness, and paresthesia crease the risk for thrombotic events (Table 1).9 The macrovascular com- and other complications, and avoid plications, often referred to as major leukemic transformation.3,12,13 The need for treatment is deterthrombotic events, are serious events that are secondary to thrombi in large mined after assessing the patient’s arteries or veins, including myocardial risk status, based on age and thrombosis history. Patients aged >60 years infarction (Table 1).10 Cardiovascular events are the pri- or those with a history of thrombosis mary cause of mortality in patients have high-risk polycythemia vera, with polycythemia vera, accounting whereas younger patients aged <60 for 45% of deaths.11 Other major years or those with no history of causes of death in this patient popula- thrombosis have low-risk disease.3,13 tion include solid tumors (20%) and Patients with low-risk polycythemia hematologic transformations (13%).11 vera are often phlebotomized and Although polycythemia vera is in- receive low-dose aspirin. Conversely, curable, it can be managed effectively patients with high-risk disease refor long periods.3 The treatment of quire medical therapy to lower their patients with polycythemia vera is hematocrit concentration permadesigned to reduce the hematocrit nently (ie, <45% in men and <42% and platelet concentrations, control in women), eliminate the need for Continued on page 48

June 2015

www.OncPracticeManagement.com

For patients with bone metastases from solid tumors

Prevent bone complications longer In a prespeciﬁed integrated analysis of 3 pivotal trials (N = 5,723),

8.2

XGEVA® was proven to delay the median time to first bone complication by

months longer vs zoledronic acid1

XGEVA® is a convenient 120 mg subcutaneous injection administered once every 4 weeks.2

Bone complications, or skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.2,3 Median Time to First Bone Complication1 27.7

months

XGEVA VA® 120 mg Q4W (n = 2,862) VA

Data from a prespecified integrated analysis of three international, phase 3, double-blind, double-dummy, active-controlled trials comparing XGEVA® with zoledronic acid for the prevention of bone complications in patients with bone metastases from solid tumors or multiple myeloma.1

19.5

months

zoledronic acid 4 mg Q4W (n = 2,861) 1 YEAR

HR* = 0.83 (95% CI: 0.76-0.90)

2 YEARS

P < 0.001†

IMPORTANT SAFETY INFORMATION Hypocalcemia • Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®. XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA® is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia. • An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake. Hypersensitivity • XGEVA® is contraindicated in patients with known clinically signiﬁcant hypersensitivity to XGEVA®, including anaphylaxis that has been reported with use of XGEVA®. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically signiﬁcant allergic reaction occurs, initiate appropriate therapy and discontinue XGEVA® therapy permanently.

*Hazard ratio (HR) is defined as the increase or decrease in likelihood of an event of interest (in this case a bone complication) for one group relative to that in a comparator group. P value for superiority.

†

Drug Products with Same Active Ingredient • Patients receiving XGEVA® should not take Prolia® (denosumab). Osteonecrosis of the Jaw • Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA®, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with osseous metastasis, the incidence of ONJ was higher with longer duration of exposure. • Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA® and periodically during XGEVA® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA®. • Patients who are suspected of having or who develop ONJ while on XGEVA® should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition. Atypical Subtrochanteric and Diaphyseal Femoral Fracture • Atypical femoral fracture has been reported with XGEVA®. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar ﬂare and are transverse or short oblique in orientation without evidence of comminution.

XGEVA® is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. XGEVA® is not indicated for the prevention of skeletal-related events in patients with multiple myeloma. • RANK Ligand (RANKL) is produced by bone cells in the skeleton and is a key mediator of bone resorption4 • RANKL production is increased at sites of bone metastases, and stimulates osteoclasts to destroy bone4 • XGEVA® acts precisely to bind RANKL and inhibits osteoclast formation, function, and survival2 • Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®2

Learn more at XGEVA.com

• Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During XGEVA® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of XGEVA® therapy should be considered, pending a risk/beneﬁt assessment, on an individual basis.

Embryo-Fetal Toxicity • XGEVA® can cause fetal harm when administered to a pregnant woman. Based on ﬁndings in animals, XGEVA® is expected to result in adverse reproductive effects.

• Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after the last dose of XGEVA®. Apprise the patient of the potential hazard to a fetus if XGEVA® is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA®.

Adverse Reactions • The most common adverse reactions in patients receiving XGEVA® with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia. Please see brief summary of Prescribing Information on the following page. REFERENCES: 1. Lipton A, Fizazi K, Stopeck AT, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012;48:30823092. 2. XGEVA® (denosumab) prescribing information, Amgen. 3. Brodowicz T, O’Byrne K, Manegold C. Bone matters in lung cancer. Ann Oncol. 2012;23:22152222. 4. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350:1655-1664.

www.XGEVA.com

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Brief Summary: Consult package insert for complete Prescribing Information

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INDICATIONS AND USAGE: Bone Metastasis from Solid Tumors. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. Important Limitation of Use. Xgeva is not indicated for the prevention of skeletal-related events in patients with multiple myeloma. DOSAGE AND ADMINISTRATION: Recommended Dosage. The recommended dose of Xgeva is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia. Preparation and Administration. Visually inspect Xgeva for particulate matter and discoloration prior to administration. Xgeva is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles. Do not use if the solution is discolored or cloudy or if the solution contains many particles or foreign particulate matter. Prior to administration, Xgeva may be removed from the refrigerator and brought to room temperature (up to 25°C/77°F) by standing in the original container. This generally takes 15 to 30 minutes. Do not warm Xgeva in any other way. Use a 27-gauge needle to withdraw and inject the entire contents of the vial. Do not re-enter the vial. Discard vial after single-use or entry. CONTRAINDICATIONS: Hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating therapy with Xgeva. Hypersensitivity. Xgeva is contraindicated in patients with known clinically significant hypersensitivity to Xgeva. WARNINGS AND PRECAUTIONS: Drug Products with Same Active Ingredient. Xgeva includes the same active ingredient (denosumab) found in Prolia. Patients receiving Xgeva should not take Prolia. Hypersensitivity. Clinically significant hypersensitivity including anaphylaxis has been reported with use of Xgeva. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue Xgeva therapy permanently. Hypocalcemia. Xgeva can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Correct pre-existing hypocalcemia prior to Xgeva treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when Xgeva is administered with other drugs that can also lower calcium levels. In the postmarketing setting, severe symptomatic hypocalcemia has been reported. Advise patients to contact a healthcare professional for symptoms of hypocalcemia. An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake. Osteonecrosis of the Jaw. Osteonecrosis of the jaw (ONJ) can occur in patients receiving Xgeva, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials, in patients with osseous metastasis, the incidence of ONJ was higher with longer duration of exposure (see Adverse Reactions). Seventy-nine percent of patients with ONJ had a history of tooth extraction, poor oral hygiene, or use of a dental appliance as a predisposing factor. Perform an oral examination and appropriate preventive dentistry prior to the initiation of Xgeva and periodically during Xgeva therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with Xgeva. Patients who are suspected of having or who develop ONJ while on Xgeva should

receive care by a dentist or an oral surgeon. In these on-study was 13 months (range: 0.1 – 41). Of patients patients, extensive dental surgery to treat ONJ may who received Xgeva, 46% were female. Eighty-five exacerbate the condition. percent were White, 5% Hispanic/Latino, 6% Asian, and Atypical Subtrochanteric and Diaphyseal Femoral 3% Black. The median age was 63 years (range: 18 – 93). Fracture. Atypical femoral fracture has been reported Seventy-five percent of patients who received Xgeva with Xgeva. These fractures can occur anywhere in the received concomitant chemotherapy. femoral shaft from just below the lesser trochanter to Table 1. Per-patient Incidence of Selecteda Adverse above the supracondylar flare and are transverse or short Reactions of Any Severity (Trials 1, 2, and 3) oblique in orientation without evidence of comminution. Zoledronic Atypical femoral fractures most commonly occur with Xgeva Acid minimal or no trauma to the affected area. They may Body System n = 2841 n = 2836 % be bilateral and many patients report prodromal pain % in the affected area, usually presenting as dull, aching GASTROINTESTINAL thigh pain, weeks to months before a complete fracture 32 31 Nausea occurs. A number of reports note that patients were also 19 20 Diarrhea receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During Xgeva treatment, patients GENERAL should be advised to report new or unusual thigh, hip, or Fatigue/ Asthenia 45 46 groin pain. Any patient who presents with thigh or groin IN VESTIGATIONS pain should be suspected of having an atypical fracture Hypocalcemiab 9 18 and should be evaluated to rule out an incomplete femur 20 32 Hypophosphatemiab fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and NEUROLOGICAL signs of fracture in the contralateral limb. Interruption Headache 13 14 of Xgeva therapy should be considered, pending a risk/ RESPIRATORY benefit assessment, on an individual basis. 18 21 Dyspnea EMBRYO-FETAL TOXICITY: Xgeva can cause fetal harm 15 15 Cough when administered to a pregnant woman. Based on findings in animals, Xgeva is expected to result in adverse a Adverse reactions reported in at least 10% of patients reproductive effects. In utero denosumab exposure in receiving Xgeva in Trials 1, 2, and 3, and meeting one cynomolgus monkeys resulted in increased fetal loss, of the following criteria: stillbirths, and postnatal mortality, along with evidence of • At least 1% greater incidence in Xgeva-treated absent peripheral lymph nodes, abnormal bone growth, patients, or and decreased neonatal growth (see Use in Specific • Between-group difference (either direction) of less than Populations). Advise females of reproductive potential 1% and more than 5% greater incidence in patients to use highly effective contraception during therapy, treated with zoledronic acid compared to placebo (US and for at least 5 months after with the last dose of Prescribing Information for zoledronic acid) Xgeva. Apprise the patient of the potential hazard to a b Laboratory-derived and below the central laboratory lower fetus if Xgeva is used during pregnancy or if the patient limit of normal [8.3 – 8.5 mg/dL (2.075 – 2.125 mmol/L) becomes pregnant while patients are exposed to Xgeva. for calcium and 2.2 – 2.8 mg/dL (0.71 – 0.9 mmol/L) Advise patients to contact their healthcare provider for phosphorus] if they become pregnant or a pregnancy is suspected Severe Mineral/Electrolyte Abnormalities during this time. • Severe hypocalcemia (corrected serum calcium less ADVERSE REACTIONS: The following adverse reactions than 7 mg/dL or less than 1.75 mmol/L) occurred are discussed below and elsewhere in the labeling: in 3.1% of patients treated with Xgeva and 1.3% of • Hypocalcemia patients treated with zoledronic acid. Of patients who experienced severe hypocalcemia, 33% experienced • Osteonecrosis of the Jaw The most common adverse reactions in patients receiving 2 or more episodes of severe hypocalcemia and 16% Xgeva (per-patient incidence greater than or equal to 25%) experienced 3 or more episodes. were fatigue/asthenia, hypophosphatemia, and nausea • Severe hypophosphatemia (serum phosphorus less (see Table 1). The most common serious adverse reaction than 2 mg/dL or less than 0.6 mmol/L) occurred in in patients receiving Xgeva was dyspnea. The most 15.4% of patients treated with Xgeva and 7.4% of common adverse reactions resulting in discontinuation of patients treated with zoledronic acid. Xgeva were osteonecrosis and hypocalcemia. Osteonecrosis of the Jaw Clinical Trials Experience. Because clinical trials are In the primary treatment phases of Trials 1, 2, and 3, conducted under widely varying conditions, adverse ONJ was confirmed in 1.8% of patients in the Xgeva group reaction rates observed in the clinical trials of a drug (median exposure of 12.0 months; range 0.1 – 40.5) cannot be directly compared to rates in other clinical and 1.3% of patients in the zoledronic acid group. The trials and may not reflect the rates observed in practice. trials in patients with breast (Trial 1) or prostate (Trial The safety of Xgeva was evaluated in three randomized, 3) cancer included an Xgeva open label extension double-blind, double-dummy trials in which a total treatment phase where patients were offered Xgeva 120 of 2841 patients with bone metastasis from prostate mg once every 4 weeks (median overall exposure of 14.9 cancer, breast cancer, or other solid tumors, or lytic bony months; range 0.1 – 67.2). The patient-year adjusted lesions from multiple myeloma received at least one dose incidence of confirmed ONJ was 1.1% during the first of Xgeva. In Trials 1, 2, and 3, patients were randomized year of treatment and 4.1% thereafter. The median time to receive either 120 mg of Xgeva every 4 weeks as to ONJ was 20.6 months (range: 4 – 53). a subcutaneous injection or 4 mg (dose adjusted for Atypical Subtrochanteric and Diaphyseal Fracture reduced renal function) of zoledronic acid every 4 weeks Atypical femoral fracture has been reported with Xgeva. by intravenous (IV) infusion. Entry criteria included serum calcium (corrected) from 8 to 11.5 mg/dL (2 to Postmarketing Experience. Because postmarketing 2.9 mmol/L) and creatinine clearance 30 mL/min or reactions are reported voluntarily from a population greater. Patients who had received IV bisphosphonates of uncertain size, it is not always possible to reliably were excluded, as were patients with prior history of estimate their frequency or establish a causal relationship ONJ or osteomyelitis of the jaw, an active dental or jaw to drug exposure. condition requiring oral surgery, non-healed dental/ The following adverse reactions have been identified oral surgery, or any planned invasive dental procedure. during post approval use of Xgeva: During the study, serum chemistries including calcium • Hypocalcemia: Severe symptomatic hypocalcemia, and phosphorus were monitored every 4 weeks. Calcium including fatal cases. and vitamin D supplementation was recommended but • Hypersensitivity, including anaphylactic reactions. not required. The median duration of exposure to Xgeva • Musculoskeletal pain, including severe musculoskeletal was 12 months (range: 0.1 – 41) and median duration pain. Positive rechallenge has been reported.

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to normal; there were no adverse effects on tooth eruption, though dental dysplasia was still apparent; axillary and inguinal lymph nodes remained absent, while mandibular and mesenteric lymph nodes were present, though small; and minimal to moderate mineralization in multiple tissues was seen in one recovery animal. There was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor. Maternal mammary gland development was normal. There was no fetal NOAEL (no observable adverse effect level) established for this study because only one dose of 50 mg/kg was evaluated. In RANKL knockout mice, absence of RANKL (the target of denosumab) also caused fetal lymph node agenesis and led to postnatal impairment of dentition and bone growth. Pregnant RANKL knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation. Nursing Mothers. It is not known whether Xgeva is excreted into human milk. Measurable concentrations of denosumab were present in the maternal milk of cynomolgus monkeys up to 1 month after the last dose of denosumab (≤ 0.5% milk:serum ratio). Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Xgeva, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Maternal exposure to Xgeva during pregnancy may impair mammary gland development and lactation based on animal studies in pregnant mice lacking the RANK/ RANKL signaling pathway that have shown altered maturation of the maternal mammary gland, leading to impaired lactation postpartum. However, in cynomolgus monkeys treated with denosumab throughout pregnancy, maternal mammary gland development was normal, with no impaired lactation. Mammary gland histopathology at 6 months of age was normal in female offspring exposed to denosumab in utero; however, development and lactation have not been fully evaluated. Pediatric Use. Xgeva is not recommended in pediatric patients. The safety and effectiveness of Xgeva in pediatric patients have not been established. Treatment with Xgeva may impair bone growth in children with open growth plates and may inhibit eruption of dentition. In neonatal rats, inhibition of RANKL (the target of Xgeva therapy) with a construct of osteoprotegerin bound to Fc (OPG-Fc) at doses ≤ 10 mg/kg was associated with inhibition of bone growth and tooth eruption. Adolescent primates treated with denosumab at doses 5 and 25 times (10 and 50 mg/kg dose) higher than the recommended human dose of 120 mg administered once every 4 weeks, based on body weight (mg/kg), had abnormal growth plates, considered to be consistent with the pharmacological activity of denosumab. Cynomolgus monkeys exposed in utero to denosumab exhibited bone abnormalities, reduced hematopoiesis, tooth malalignment, decreased neonatal growth, and an absence of axillary, inguinal, mandibular, and mesenteric lymph nodes. Some bone abnormalities recovered once exposure was ceased following birth; however, axillary and inguinal lymph nodes remained absent 6 months post-birth. Geriatric Use. Of patients who received Xgeva in Trials 1, 2, and 3, 1260 (44%) were 65 years of age or older. No overall differences in safety or efficacy were observed between these patients and younger patients. Renal Impairment. Two clinical trials were conducted in patients without cancer and with varying degrees of renal function. In one study, patients (N=55) with varying degrees of renal function (ranging from normal through end-stage renal disease requiring dialysis) received a single 60 mg subcutaneous dose of denosumab. In a second study, patients (N=32) with severe renal dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis) were given two 120 mg subcutaneous doses of denosumab. In both studies, greater risk of developing hypocalcemia was observed with increasing renal impairment, and with inadequate/ no calcium supplementation. Hypocalcemia was mild to moderate in severity in 96% of patients. Monitor calcium levels and, calcium and vitamin D intake.

DOUS14CDNY4736_A_XGEVA_Asize_BS_V10_8pt_r10.indd 2

Females and Males of Reproductive Potential. Contraception Females: Counsel patients on pregnancy planning and prevention. Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after the last dose of Xgeva. Advise patients to contact their healthcare provider if they become pregnant, or a pregnancy is suspected, during treatment or within 5 months after the last dose of Xgeva. Males: The extent to which denosumab is present in seminal fluid is unknown. There is potential for fetal exposure to denosumab when a male treated with Xgeva has unprotected sexual intercourse with a pregnant partner. Advise males of this potential risk. OVERDOSAGE: There is no experience with overdosage of Xgeva. HOW SUPPLIED/STORAGE AND HANDLING: Xgeva is supplied in a single-use vial. Store Xgeva in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton. Do not freeze. Once removed from the refrigerator, Xgeva must not be exposed to temperatures above 25°C/77°F or direct light and must be used within 14 days. Discard Xgeva if not used within the 14 days. Do not use Xgeva after the expiry date printed on the label. Protect Xgeva from direct light and heat. Avoid vigorous shaking of Xgeva. PATIENT COUNSELING INFORMATION: Advise patients to contact a healthcare professional for any of the following: • Symptoms of a hypersensitivity reaction, including rash, urticaria, pruritus, lip swelling, shortness of breath, hypotension and respiratory tract edema • Symptoms of hypocalcemia, including paresthesias or muscle stiffness, twitching, spasms, or cramps • Symptoms of ONJ, including pain, numbness, swelling of or drainage from the jaw, mouth, or teeth • Persistent pain or slow healing of the mouth or jaw after dental surgery • Symptoms of atypical femoral fracture, including new or unusual thigh, hip, or groin pain • Pregnancy or nursing Advise patients of the need for: • Avoiding therapy with Xgeva if a serious allergic reaction occurred with prior Xgeva or Prolia therapy • Proper oral hygiene and routine dental care • Informing their dentist that they are receiving Xgeva • Avoiding invasive dental procedures during treatment with Xgeva • The use of highly effective contraception during and for at least 5 months after treatment with Xgeva for females of reproductive potential Advise patients that denosumab is also marketed as Prolia®. Patients should inform their healthcare provider if they are taking Prolia.

8/11/14 11:56 AM

S:9.875”

Immunogenicity. As with all therapeutic proteins, there is potential for immunogenicity. Using an electrochemiluminescent bridging immunoassay, less than 1% (7/2758) of patients with osseous metastases treated with denosumab doses ranging from 30 – 180 mg every 4 weeks or every 12 weeks for up to 3 years tested positive for binding antibodies. No patient with positive binding antibodies tested positive for neutralizing antibodies as assessed using a chemiluminescent cellbased in vitro biological assay. There was no evidence of altered pharmacokinetic profile, toxicity profile, or clinical response associated with binding antibody development. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of a positive antibody (including neutralizing antibody) test result may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of antibodies to denosumab with the incidence of antibodies to other products may be misleading. DRUG INTERACTIONS: No formal drug-drug interaction trials have been conducted with Xgeva. In clinical trials in patients with breast cancer metastatic to bone, Xgeva was administered in combination with standard anticancer treatment. Serum denosumab concentrations at 1 and 3 months and reductions in the bone turnover marker uNTx/Cr (urinary N-terminal telopeptide corrected for creatinine) at 3 months were similar in patients with and without prior intravenous bisphosphonate therapy. There was no evidence that various anticancer treatments affected denosumab systemic exposure and pharmacodynamic effect. Serum denosumab concentrations at 1 and 3 months were not altered by concomitant chemotherapy and/or hormone therapy. The median reduction in uNTx/Cr from baseline to month 3 was similar between patients receiving concomitant chemotherapy and/or hormone therapy. USE IN SPECIFIC POPULATIONS: Pregnancy: Category D. Risk Summary: Xgeva can cause fetal harm when administered to a pregnant woman based on findings in animals. In utero denosumab exposure in cynomolgus monkeys resulted in increased fetal loss, stillbirths, and postnatal mortality, along with evidence of absent lymph nodes, abnormal bone growth and decreased neonatal growth. There are no adequate and well-controlled studies with Xgeva in pregnant women. Women should be advised not to become pregnant when taking Xgeva. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women who become pregnant during Xgeva treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll. Clinical Considerations: The effects of Xgeva are likely to be greater during the second and third trimesters of pregnancy. Monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester. If the patient becomes pregnant during Xgeva therapy, consider the risks and benefits in continuing or discontinuing treatment with Xgeva. Animal Data: The effects of denosumab on prenatal development have been studied in both cynomolgus monkeys and genetically engineered mice in which RANK ligand (RANKL) expression was turned off by gene removal (a “knockout mouse”). In cynomolgus monkeys dosed subcutaneously with denosumab throughout pregnancy at a pharmacologically active dose, there was increased fetal loss during gestation, stillbirths, and postnatal mortality. Other findings in offspring included absence of axillary, inguinal, mandibular, and mesenteric lymph nodes; abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia and tooth malalignment; and decreased neonatal growth. At birth out to one month of age, infants had measurable blood levels of denosumab (22-621% of maternal levels). Following a recovery period from birth out to 6 months of age, the effects on bone quality and strength returned

Drug Update

Jakafi (Ruxolitinib): First FDA-Approved... Continued from page 43 phlebotomy, and decrease the risk for clotting.3,13 Cytoreductive therapy is recommended to control red blood cell volume in patients for whom phlebotomy is poorly tolerated, in patients with a high thrombotic risk, and in those with symptomatic splenomegaly.3 Among the available cytoreductive medication options, hydroxyurea is currently the treatment of choice for patients with polycythemia vera who are older than 40 years.12-14 Although it effectively improves myelosuppression and reduces the risk for thrombosis compared with phlebotomy alone, hydroxyurea’s utility is limited by its risk for secondary leukemia.14,15 Patients who are intolerant of or are resistant to hydroxyurea can be effectively managed with pegylated interferon (IFN)-alpha or with busulfan.16 A 2011 article recommends the use of IFN-alpha for the treatment of patients with polycythemia vera aged <65 years, and the use of busulfan in older patients, although no other evidence is available to validate this recommendation.16 Data regarding the economic burden of polycythemia vera and other myeloproliferative neoplasms are sparse. However, a study presented at the 2011 annual meeting of the American Society of Hematology demonstrated that the medical costs for patients with myeloproliferative neoplasms are significant and are up to 6 times higher than the medical costs incurred by patients with other noncancer conditions.17 The inves tigators assessed the medical costs of more than 25,000 patients with myeloproliferative neoplasms using claims data from approximately 100 US-based payers. Patients with myelofibrosis incurred the highest total annual costs, averaging $34,690, with outpatient costs accounting for the majority of the costs. The total

medical costs for patients with essential thrombocythemia averaged $19,672, and $11,927 for patients with polycythemia vera.17

Ruxolitinib First Therapy Approved by the FDA for Polycythemia Vera On December 4, 2014, the US Food and Drug Administration (FDA) approved ruxolitinib (Jakafi; Incyte Corporation), an oral kinase

cy over the other available therapy for polycythemia vera at the time its application was submitted. In addition, ruxolitinib received an orphan drug designation.18 Polycythemia vera is the second indication for ruxolitinib. Ruxolitinib was first approved by the FDA in November 2011 for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, postpolycythemia vera

“The approval of Jakafi for polycythemia vera underscores the importance of developing drugs matched to our increasing knowledge of the mechanisms of diseases. The trial used to evaluate Jakafi confirmed clinically meaningful reductions in spleen size and the need for phlebotomies to control the disease.” inhibitor, for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.18,19 Ruxolitinib is the first drug approved by the FDA for the treatment of polycythemia vera.18 “The approval of Jakafi for polycythemia vera underscores the importance of developing drugs matched to our increasing knowledge of the mechanisms of diseases,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The trial used to evaluate Jakafi confirmed clinically meaningful reductions in spleen size and the need for phlebotomies to control the disease.”18 The FDA approved ruxolitinib under its priority review program, because the medication demonstrated the potential to provide significant improvement in safety or effica-

myelofibrosis, and postessential thrombocythemia myelofibrosis.18,20

Mechanism of Action Polycythemia vera is associated with dysregulated JAK1 and JAK2 signaling. Ruxolitinib inhibits JAK1 and JAK2; these kinases mediate the signaling of cytokines and growth factors that are important for hematopoiesis and for immune function. JAK signaling involves the recruitment of signal transducers and activators of transcription (STATs) to cytokine receptors, as well as the activation and the subsequent localization of STATs to the cell nucleus. This process results in the modulation of gene expression.19 Dosing and Administration The starting dose of ruxolitinib is 10 mg taken orally twice daily with or without food. The doses of ruxolitinib can be altered based on the drug’s safety and efficacy.19 The drug Continued on page 50

Oncology Practice Management

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Innovations in Oncology Management A newsletter series for oncology practice administrators, administrative staff, advanced practice clinicians, and oncology pharmacists. The series will provide concise, up-to-date information on current issues that are impacting the business of oncology.

Good Manufacturing Process

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

InnovationsInOncologyManagement.com anagement.com Supported by funding from Celgene Corporation and Celgene Patient Support. Manufacturer did not influence content. EHC388 Innovations ASize_120214

Drug Update

Jakafi (Ruxolitinib): First FDA-Approved... Continued from page 48 ESPONSE: Patients with Polycythemia Vera Reaching Primary and Table 2 R Key Secondary End Points Ruxolitinib, N (%) (N = 110)

Best available therapy, N (%) (N = 112)

P value

23 (21)

1 (<1)

<.001

Durable response at week 48

21 (19)

1 (<1)

<.001

Complete hematologic remissionb at week 32

26 (24)

10 (9)

.003

Hematocrit control at week 32

66 (60)

22 (20)

—

Spleen volume reduction ≥35% from baseline at week 32

42 (38)

1 (<1)

—

Patients achieving primary/ secondary end points Response at week 32 a

Defined as hematocrit control and a ≥35% reduction from baseline in spleen volume at week 32. b Defined as hematocrit control, platelet count ≤400 × 109/L, and white blood cell count ≤10 × 109/L at week 32. Sources: Jakafi (ruxolitinib) tablets prescribing information; December 2014; Vannucchi AM, et al. N Engl J Med. 2015;372:426-435. a

labeling provides detailed recommendations for dose reduction and dose reinitiation after interruption of treatment with ruxolitinib.19

Clinical Trials The approval of ruxolitinib for the treatment of patients with polycythemia vera was based on a randomized, open-label, active-controlled phase 3 clinical trial known as the RESPONSE trial.18,19,21 In this clinical trial, ruxolitinib (10 mg twice daily) was compared with best available care in patients with polycythemia vera who had unacceptable side effects from or who had an inadequate response to hydroxyurea.19,21 The primary end point of the RESPONSE study included hematocrit control and a spleen volume reduction of ≥35% by week 32.19,21 The secondary end points included the proportion of randomized patients who reached the primary end point and maintained their response 48 weeks after randomization, and the proportion of patients who reached complete hematologic remission at week 32.19,21 A total of 222 phlebotomy-depen-

dent patients with splenomegaly received ruxolitinib (N = 110) or best available therapy (N = 112), which was determined by the investigators on an individualized basis19,21; patients in the best available therapy group typically received hydroxyurea, IFN-alpha, or no medication.21 The doses of ruxolitinib were individualized based on tolerability and efficacy, with a maximum dose of 25 mg twice daily.19,21 The majority of patients in the RESPONSE trial had been diagnosed with polycythemia vera for 8 years or longer (range, 0.5-36 years).21 Approximately 95% of patients had the JAK2 V617F mutation.21 The patients’ median age was 61 years (range, 33-90 years), with 30% of patients aged >65 years.19,21 Overall, 66% of patients were male.19 The median spleen volume was 1272 cm3 (range, 254 cm3-5147 cm3), and the median palpable spleen length below the costal margin was 7 cm.19,21 As shown in Table 2, 21% of patients who received ruxolitinib reached the primary end point compared with <1% of patients who received best available therapy.19,21

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The majority (77%) of patients in the ruxolitinib group reached at least 1 component of the primary end point by week 32.21 The results of the secondary end point analyses also favored ruxolitinib.19,21 The likelihood that the response to therapy was maintained 48 weeks after randomization was higher in patients who received ruxolitinib compared with patients who received best available therapy. In addition, a significantly larger proportion of patients who received ruxolitinib reached complete hematologic remission at week 32 compared with patients who received best available therapy.19,21

Safety The safety of ruxolitinib has been assessed in 617 patients who participated in 1 of 6 clinical trials.19 The median duration of follow-up was 10.9 months.19 This cohort included 110 patients with polycythemia vera whose disease was resistant to or who were intolerant of hydroxyurea in the RESPONSE clinical trial19; in this study, the most frequent adverse drug reaction was anemia.19 Table 3 lists the most common nonhematologic treatment-emergent adverse events that occurred up to week 32 in the RESPONSE trial, which included headaches, abdominal pain, and diarrhea.19 Other clinically important treatment-emergent adverse events that were noted in <6% of patients who received ruxolitinib were weight gain, hypertension, and urinary tract infections.19 Of the patients who received ruxolitinib in the RESPONSE trial, 4% discontinued the use of the drug as a result of adverse events.19 Ruxolitinib has no contraindications. Warnings and Precautions Thrombocytopenia, anemia, and

Drug Update

neutropenia. Thrombocytopenia, anemia, and neutropenia can occur after treatment with ruxolitinib. Thrombocytopenia should be managed by reducing the dose of ruxolitinib or by temporarily interrupting its use; platelet transfusions may be required. If anemia occurs, blood transfusions and/or dose modification of ruxolitinib may be necessary. Severe neutropenia is generally reversible after the discontinuation of ruxolitinib therapy. Patients should undergo a complete blood count before starting treatment with ruxolitinib, followed by every 2 to 4 weeks until the doses are stabilized.19 Risk for infection. Ruxolitinib has been associated with serious bacterial, mycobacterial, fungal, and viral infections. Ruxolitinib therapy should not be started until active serious infections have resolved. Patients who receive ruxolitinib should be observed for the signs and symptoms of infection and should be managed promptly.19 Tuberculosis has been reported in patients who received ruxolitinib. Patients should be evaluated for tuberculosis risk before starting ruxolitinib therapy. Patients at high risk for tuberculosis should be tested for latent infection. If evidence of active or latent tuberculosis is found, a physician with expertise in the treatment of tuberculosis should be consulted before starting ruxolitinib therapy. The decision to continue ruxolitinib therapy while active tuberculosis is being treated should be based on the overall riskâ&#x20AC;&#x201C;benefit determination.19 Progressive multifocal leukoencephalopathy (PML) has occurred with ruxolitinib in the treatment of patients with myelofibrosis. The use of ruxolitinib therapy should be discontinued if PML is suspected.19 Patients who receive ruxolitinib should be advised about the early signs and symptoms of herpes zoster and should seek treatment if it is suspected.19

Table 3 RESPONSE: Treatment-Emergent Adverse Events in â&#x2030;Ľ6% of Patients Receiving Ruxolitinib Up to Week 32 Patients receiving ruxolitinib (N = 110)

Patients receiving best available therapy (N = 111)

All grades,a Grade 3-4,a All grades,a Grade 3-4,a % % % %

Adverse events Headache

Abdominal pain

Diarrhea

Dizziness + vertigo

Fatigue

Dyspnea

Muscle spasms

Pruritus c

Nasopharyngitis

Constipation

Cough

Edema + peripheral edema

Arthralgia

Asthenia

Epistaxis

Herpes zoster + postherpetic neuralgia

Nausea

National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. b Including lower and upper abdominal pain. c Including dyspnea exertional. Source: Jakafi (ruxolitinib) tablets prescribing information; December 2014. a

Symptom exacerbation after ruxolitinib discontinuation. Symptoms associated with myeloproliferative neoplasms may return to pretreatment levels approximately 1 week after ruxolitinib therapy is discontinued.19 If symptoms occur, patients should be evaluated and treated for any intercurrent illness; in addition, restarting ruxolitinib therapy or increasing its dose should be considered.19 Patients should not interrupt or discontinue ruxolitinib therapy without consulting their physician. If therapy is stopped for reasons other than thrombocytopenia, the dose of ruxolitinib should be tapered.19

Nonmelanoma skin cancer. Skin cancers, including basal-cell, squamous-cell, and Merkel-cell carcinoma, have occurred in patients receiving ruxolitinib. Therefore, the skin should be examined periodically while taking ruxolitinib.19

Use in Specific Populations Pregnancy. Ruxolitinib is a pregnancy category C teratogen; there are no adequate and well-controlled studies with ruxolitinib in pregnant women. Ruxolitinib should only be used during pregnancy if the potential benefit outweighs the potential risk to the fetus.19 Continued on page 54

June 2015

www.OncPracticeManagement.com

OCTOBER 1–4 • HYATT REGENCY ATLANTA • ATLANTA, GEORGIA Our highly popular Annual Navigation and Survivorship Conference provides oncology navigation professionals with the opportunity to gain timely, relevant knowledge that will benefit them in their career while enhancing the care that they provide their patients.

MEETING HIGHLIGHTS: Stimulating educational sessions addressing topics such as:

Navigators Exploring Xtra Tracks (NEXT) for all levels of experience

• Psychosocial care for cancer patients • Commission on Cancer updates • Navigation and survivorship care planning • Strengthening navigation and survivorship programs • Providing patient support and guidance in the age of personalized cancer care • Genetic counseling

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Administrators

Practice managers

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Oncologists

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A special one-day

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Sharon Gentry, RN, MSN, AOCN, CBCN Breast Health Navigator Novant Health Derrick L. Davis Cancer Center Winston-Salem, NC

PATIENT NAVIGATION TRACK CHAIR Mandi Chapman Member of the AONN+ Leadership Council and Director, George Washington University Cancer Institute

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Drug Update

Jakafi (Ruxolitinib): First FDA-Approved... Continued from page 51 Nursing mothers. It is not known whether the components of ruxolitinib are present in human breast milk. Nursing or ruxolitinib should be discontinued on the basis of the importance of ruxolitinib to the mother.19

treatment of patients with polycythemia vera. This medication demonstrated superior efficacy in controlling hematocrit levels, reducing spleen size, and improving disease-related symptoms in a randomized clinical trial that compared oral ruxolitinib

Ruxolitinib is the first medication to receive FDA approval for the treatment of patients with polycythemia vera. This medication demonstrated superior efficacy in controlling hematocrit levels, reducing spleen size, and improving diseaserelated symptoms. Pediatric use. The safety and efficacy of ruxolitinib have not been established in patients aged <18 years.19 Geriatric use. Overall, 52% of patients with myelofibrosis in clinical studies of ruxolitinib were aged â&#x2030;Ľ65 years. No overall differences in safety or efficacy were observed between older and younger patients.19 Renal impairment. The dose of ruxolitinib should be reduced in patients with moderate or severe renal impairment, or in patients with endstage renal disease (ESRD) who are on dialysis. Ruxolitinib should not be used by patients with ESRD who are not on dialysis.19 Hepatic impairment. A dose reduction is recommended in patients with hepatic impairment; ruxolitinib should be started at 5 mg twice daily in patients with mild, moderate, or severe hepatic impairment.19

Conclusion Ruxolitinib is the first medication to receive FDA approval for the

with best available therapies, including hydroxyurea, for the treatment of patients with polycythemia vera. By contrast, best available therapies offered little to no benefit. This novel kinase inhibitor represents an important new, and the only FDA-approved, option for the treatment of patients with polycythemia vera. Clinical trials continue to explore the potential role of ruxolitinib in myeloproliferative neoplasms, as well as in other hematologic malignancies, such as acute myeloid leukemia and chronic myeloid leukemia, as well as in solid tumors, such as metastatic pancreatic cancer.21 l

References

1. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008;22:14-22. 2. Spivak JL. Polycythemia vera: myths, mechanisms, and management. Blood. 2002;100:4272-4290. 3. Leukemia & Lymphoma Society. Polycythemia vera facts. No. 13. Revised June 2012. www.lls.org/content/ nationalcontent/resourcecenter/freeeducationmaterials/ mpd/pdf/polycythemiavera.pdf. Accessed March 2, 2015. 4. Kumar C, Purandare AV, Lee FY, Lorenzi MV. Kinase drug discovery approaches in chronic myeloproliferative disorders. Oncogene. 2009;28:2305-2313.

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5. Passamonti F, Rumi E, Pietra D, et al. Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders. Blood. 2006;107:3676-3682. 6. Vannucchi AM, Antonioli E, Guglielmelli P, et al. Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia. 2008;22:1299-1307. 7. Tefferi A. Essential thrombocythemia, polycythemia vera, and myelofibrosis: current management and the prospect of targeted therapy. Am J Hematol. 2008; 83:491-497. 8. Finazzi G, Caruso V, Marchioli R, et al; for the ECLAP Investigators. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood. 2005;105:2664-2670. 9. Michiels JJ, Berneman Z, Van Bockstaele D, et al. Clinical and laboratory features, pathobiology of platelet-mediated thrombosis and bleeding complications, and the molecular etiology of essential thrombocythemia and polycythemia vera: therapeutic implications. Semin Thromb Hemost. 2006;32:174-207. 10. Falanga A, Marchetti M. Thrombotic disease in the myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program. 2012;2012:571-581. 11. Marchioli R, Finazzi G, Landolfi R, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol. 2005;23:2224-2232. 12. Barbui T, Barosi G, Birgegard G, et al; for the European LeukemiaNet. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29:761-770. 13. Finazzi G, Barbui T. Evidence and expertise in the management of polycythemia vera and essential thrombocythemia. Leukemia. 2008;22:1494-1502. 14. Weinfeld A, Swolin B, Westin J. Acute leukaemia after hydroxyurea therapy in polycythaemia vera and allied disorders: prospective study of efficacy and leukaemogenicity with therapeutic implications. Eur J Haematol. 1994;52:134-139. 15. Fruchtman SM, Mack K, Kaplan ME, et al. From efficacy to safety: a Polycythemia Vera Study Group report on hydroxyurea in patients with polycythemia vera. Semin Hematol. 1997;34:17-23. 16. Tefferi A. Annual clinical updates in hematological malignancies: a continuing medical education series: polycythemia vera and essential thrombocythemia: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol. 2011;86:292-301. 17. Price GL, Pohl GM, Xie J, Walgren RA. A retrospective observational study of annual healthcare costs for patients with forms of myeloproliferative neoplasms (MPN). Blood (ASH Annual Meeting Abstracts). 2011;118. Abstract 2060. 18. US Food and Drug Administration. FDA approves Jakafi to treat patients with a chronic type of bone marrow disease: first FDA-approved drug for polycythemia vera. Press release. December 4, 2014. www.fda. gov/NewsEvents/Newsroom/PressAnnouncements/ ucm425677.htm. Accessed March 2, 2015. 19. Jakafi (ruxolitinib) tablets [prescribing information]. Wilmington, DE: Incyte Corporation; December 2014. 20. US Food and Drug Administration. FDA approves first drug to treat a rare bone marrow disease. Press release. November 16, 2011. www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/ucm280102.htm. Accessed March 2, 2015. 21. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372:426-435.

Drug Coding Supplied by RJ Health Systems

FDA-Approved Medications Used for the Treatment of Lung Cancer The following sections will assist healthcare professionals and payers by providing appropriate coding and billing information associated with the treatment of lung cancer. The following sections include: • Associated ICD-9-CM codes used for the classification of lung cancer • Drugs that have been FDA approved in the treatment of lung cancer • Drugs that are Compendia-listed for off-label use for lung cancer based on clinical studies that suggest beneficial use in some cases. Please note: If a check mark appears in the FDA column, it will NOT appear in the Compendia off-label use column • Corresponding HCPCS/CPT® codes and code descriptions • Drugs listed in the Compendia section have no FDA-approved uses for lung cancer. However, drugs in the FDA-approved section are FDA approved for at least 1 of the lung cancer ICD-9-CM codes but may also have Compendia-listed uses as well

Associated ICD-9-CM codes for the treatment of lung cancer: 162 Malignant neoplasm of trachea, bronchus, and lung 162.0 Trachea Cartilage of trachea Mucosa of trachea 162.2 Main bronchus Carina Hilus of lung 162.3 Upper lobe, bronchus or lung 162.4 Middle lobe, bronchus or lung 162.5 Lower lobe, bronchus or lung 162.8 Other parts of bronchus or lung Malignant neoplasm of contiguous or overlapping sites of bronchus or lung whose point of origin cannot be determined 162.9 Bronchus and lung, unspecified

Generic (brand) name

HCPCS code - code description

FDA approved for lung cancer

Compendia off-label uses for lung cancer

Possible CPT® administration codes

afatinib (Gilotrif)

C9399* - Unclassified drugs or biological (hospital outpatient use ONLY)

√

N/A

afatinib (Gilotrif)

J8999* - Prescription drug, oral, chemotherapeutic, not otherwise specified

√

N/A

amifostine (Ethyol)

J0207 - Injection, amifostine, 500 mg

√

96374

Bacillus Calmette-Guérin (BCG Vaccine)

90585 - Bacillus Calmette-Guérin vaccine for tuberculosis, live, for percutaneous use

√

90471, 90472

June 2015

www.OncPracticeManagement.com

Drug Coding

Bacillus Calmette-Guérin (Theracys, Tice BCG)

90586 - Bacillus Calmette-Guérin vaccine for bladder cancer, live, for intravesical use

√

51720

Bacillus Calmette-Guérin (Theracys, Tice BCG)

J9031 - Bacillus Calmette-Guérin (intravesical), per installation

√

51720

bevacizumab (Avastin)

J9035 - Injection, bevacizumab, 10 mg

bleomycin (Blenoxane)

J9040 - Injection, bleomycin sulfate, 15 units

√

96401, 96409

carboplatin (Paraplatin)

J9045 - Injection, carboplatin, 50 mg

√

96409, 96413, 96415

ceritinib (Zykadia)

C9399* - Unclassified drugs or biological (hospital outpatient use ONLY)

√

N/A

ceritinib (Zykadia)

J8999* - Prescription drug, oral, chemotherapeutic, not otherwise specified

√

N/A

cetuximab (Erbitux)

J9055 - Injection, cetuximab, 10 mg

√

96413, 96415

cisplatin (Platinol AQ)

J9060 - Injection, cisplatin, powder or solution, per 10 mg

√

96409, 96413, 96415

crizotinib (Xalkori)

C9399* - Unclassified drugs or biological (hospital outpatient use ONLY)

√

N/A

crizotinib (Xalkori)

J8999* - Prescription drug, oral, chemotherapeutic, not otherwise specified

√

N/A

cyclophosphamide (Cytoxan)

J8530 - Cyclophosphamide, oral, 25 mg

√

N/A

cyclophosphamide (Cytoxan)

J9070 - Cyclophosphamide, 100 mg

√

96409, 96413, 96415

docetaxel (Taxotere)

J9171 - Injection, docetaxel, 1 mg

√

96413

doxorubicin HCl (Adriamycin)

J9000 - Injection, doxorubicin hydrochloride, 10 mg

√

96409

doxorubicin HCl (Doxil)

Q2050 - Injection, doxorubicin hydrochloride, liposomal, 10 mg, not otherwise specified

√

96413

epirubicin HCl (Ellence)

J9178 - Injection, epirubicin hydrochloride, 2 mg

√

96409, 96413

erlotinib (Tarceva)

C9399* - Unclassified drugs or biological (hospital outpatient use ONLY)

√

N/A

erlotinib (Tarceva)

J8999* - Prescription drug, oral, chemotherapeutic, not otherwise specified

√

N/A

etoposide (Vepesid)

J8560 - Etoposide, oral, 50 mg

√

N/A

etoposide (Etopophos, Toposar)

J9181 - Injection, etoposide, 10 mg

√

96413, 96415

fluorouracil (Adrucil)

J9190 - Injection, fluorouracil, 500 mg

Oncology Practice Management

I June 2015

96413, 96415

√

96409

Drug Coding

gefitinib (Iressa)

J8565 - Gefitinib, oral, 250 mg

√

N/A

gemcitabine HCI (Gemzar)

J9201 - Injection, gemcitabine hydrochloride, 200 mg

√

96413

ifosfamide (Ifex)

J9208 - Injection, ifosfamide, 1 g

√

96413, 96415

irinotecan (Camptosar)

J9206 - Injection, irinotecan, 20 mg

√

96413, 96415

lomustine (CeeNU)

J8999* - Prescription drug, oral, chemotherapeutic, not otherwise specified

√

N/A

lomustine (CeeNU)

S0178 - Lomustine, oral, 10 mg

√

N/A

mechlorethamine HCl (Mustargen)

J9230 - Injection, mechlorethamine hydrochloride (nitrogen mustard), 10 mg

√

96409

methotrexate (Trexall)

J8610 - Methotrexate, oral, 2.5 mg

√

N/A

methotrexate

J9250 - Methotrexate sodium, 5 mg

√

96372, 96374, 96401, 96409, 96450

methotrexate

J9260 - Methotrexate sodium, 50 mg

√

96372, 96374, 96401, 96409, 96450

metoclopramide HCI (Reglan IV only)

J2765 - Injection, metoclopramide hydrochloride, up to 10 mg

√

96372, 96374

mitomycin (Mutamycin)

J9280 - Injection, mitomycin, 5 mg

√

96409

nivolumab (Opdivo)

C9399* - Unclassified drugs or biological (hospital outpatient use ONLY)

√

96413, 96415

nivolumab (Opdivo)

J9999* - Not otherwise classified, antineoplastic drugs

√

96413, 96415

oxaliplatin (Eloxatin)

J9263 - Injection, oxaliplatin, 0.5 mg

paclitaxel protein-bound particles (Abraxane)

J9264 - Injection, paclitaxel proteinbound particles, 1 mg

√

96413

paclitaxel (Taxol)

J9265 - Injection, paclitaxel, 30 mg

√

96413, 96415

panitumumab (Vectibix)

J9303 - Injection, panitumumab, 10 mg

pemetrexed (Alimta)

J9305 - Injection, pemetrexed, 10 mg

√

96409

porfimer sodium (Photofrin)

J9600 - Injection, porfimer sodium, 75 mg

√

96409

ramucirumab (Cyramza)

C9025 - Injection, ramucirumab, 5 mg

√

96413, 96415

√

June 2015

96413, 96415

www.OncPracticeManagement.com

Drug Coding

96413, 96415

ramucirumab (Cyramza)

J9999* - antineoplastic drugs, not otherwise classified

tamoxifen (Nolvadex)

J8999* - Prescription drug, oral, chemotherapeutic, not otherwise specified

√

N/A

tamoxifen (Nolvadex)

S0187 - Tamoxifen citrate, oral, 10 mg

√

N/A

temozolomide (Temodar)

J8700 - Temozolomide, oral, 5 mg

√

N/A

teniposide (Vumon)

Q2017 - Injection, teniposide, 50 mg

√

96413, 96415

topotecan (Hycamtin)

J8705 - Topotecan, oral, 0.25 mg

√

N/A

topotecan (Hycamtin)

J9351 - Injection, topotecan, 0.1 mg

√

96413

trastuzumab (Herceptin)

J9355 - Injection, trastuzumab, 10 mg

√

96413, 96415

vinBLAStine (Velban)

J9360 - Injection, vinblastine sulfate, 1 mg

√

96409

vinCRIStine (Vincasar PFS)

J9370 - Vincristine sulfate, 1 mg

√

96409

vinorelbine (Navelbine)

J9390 - Injection, vinorelbine tartrate, per 10 mg

√

96409

*When billing a nonclassified medication using a CMS 1500 claim form, you must include both the HCPCS code (ie, J9999 for Cyramza) in Item 24D and the drug name, strength, and NDC (National Drug Code) in Item 19 or 24A (shaded area) in order to ensure appropriate reimbursement. Please note: Check with payer regarding correct placement of medication information in Item 19 or 24A. References • HCPCS Level II Expert 2015 • Current Procedural Terminology (CPT ®) 2015 • CPT copyright 2015 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association • ICD-9-CM for Professionals Volumes 1 & 2, 2015 • FDA-approved indication (product Prescribing Information) • Compendia references available upon request • www.ReimbursementCodes.com powered by RJ Health Systems International, LLC, Rocky Hill, CT • CMS (Centers for Medicare & Medicaid Services) HCPCS indicates Healthcare Common Procedure Coding System; IV, intravenous.

This information was supplied by

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Oncology Practice Management

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RJ Health Systems The Creators of ReimbursementCodes.com

RJ Health Systems â&#x20AC;&#x201D; the pharmaceutical specialists that healthcare professionals have turned to since 1983 for their drug information. We work with over 170 Payor organizations that touch approximately 110 million lives. RJ Health Systems has established and continuously maintains a Library of Drug Intelligence that provides the most comprehensive, trusted, and up-to-date coding and reimbursement information in the industry. ReimbursementCodes.com incorporates the CMS HCPCS and AMA CPT Drug codes into a system that crosswalks each drug code with the drugâ&#x20AC;&#x2122;s NDC and brand/generic name. Please visit www.rjhealthsystems.com to learn more about our products and services listed below:

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NOW JOIN US NOW IN REVEAL Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (NCT02252159) The REVEAL study is a multicenter, non-interventional, non-randomized, prospective, observational study in an adult population (patients ≥18 years old) of men and women who have been diagnosed with clinically overt PV.

Patients with PV N=2000

Study start

SCREENING

START OBSERVATION

Usual Care 36 months

DATA COLLECTION

Key Inclusion Criteria

Key Exclusion Criteria

• Age ≥18 years, diagnosis of polycythemia vera (PV) • Willing and able to provide signed informed consent • Under the supervision of US physician

• • • • •

End of study

END OBSERVATION

Participation in a blinded study Life expectancy <6 months Diagnosis of MF, PPV-MF, PET-MF Diagnosis of acute myelocytic leukemia (AML) Diagnosis of Myelodysplastic Syndrome

To join us as an investigative site in REVEAL:

Incyte REVEAL Study Hotline: 1-855-REVEAL-9

RevealPVStudy.com

Info@RevealPVStudy.com