OPM March 2015 | Vol 5 | No 2

March 2015

www.OncPracticeManagement.com

Title

Volume 5 • Number 2

Oncology Practice Management ™

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

The Evolving Oncology Medical Home

By Dawn Holcombe, MBA, FACMPE, ACHE; President, DGH Consulting, South Windsor, CT

New Model Is Announced for Oncology Care

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new payment model announced by the US Department of Health & Human Services offers providers the potential to receive at least $160 per month for patients who are undergoing chemotherapy treatment.

The per-beneficiary, per-month (PBPM)

allocation is part of a 2-pronged approach that also includes a performance-based payment to incentivize practices to reduce costs and improve care for this patient population.

The goal of this new model, known as the Oncology Care Model (OCM) and Continued on page 6

Ira M. Klein, MD, MBA, FACP

D

Michael Kolodziej, MD

irectors from Aetna, Inc, gathered recently with a panel of thought leaders to explore the evolution of the oncology medical home (OMH) against the backdrop of the company’s experiences in this area. The discussion, held in November at the Cancer Center Business Summit, highlighted initiatives Aetna has undertaken and options the company has explored in recent years.

The World of Reimbursement Is Changing: Is Your Practice Ready?

By Jessica Turgon, ECG Management Consultants, Inc

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ancer care expenditures in the United States are staggering, and are only expected to climb. In 2010, the total cost of cancer care was $125 billion.1 By 2020, with more individuals living with cancer as a chronic disease, costs are expected to grow by 39% and exceed $170 billion.1 Faced with this dramatic escalation of costs,

providers, commercial payers, and the government are testing different methodologies for reimbursing cancer care. The aim is to shift the economics from a feefor-service environment (ie, buy and bill) to one that rewards quality, efficiency, and a lower cost of care (Figure 1).

The full transition to value-based reimbursement will likely be one of trial Continued on page 10

Continued on page 16 From the publishers of

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INTEGRATING ONCOLOGISTS, PAYERS, AND THE ENTIRE CANCER CARE TEAM

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s nt ie t a 30 l r P r… a i o f e tr ay anc l W a er in C ic d n n ra li s U th B l c a i Tri w

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© 2015 Engage Healthcare Communications, LLC

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Printed in USA

Table of Contents March 2015 • Volume 5 • Number 2

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 Editorial Directors Dalia Buffery dbuffery@the-lynx-group.com Anne Cooper acooper@the-lynx-group.com Associate Editor Lara J. Lorton Editorial Assistant Cara Guglielmon 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 Director, Digital Media Anthony Romano Jr Digital Media Specialist Charles Easton IV Web Content Manager Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Mezzacappa Project Managers Deanna Martinez Jeremy Shannon Project Coordinator Rachael Baranoski IT Manager Kashif Javaid Administrative Services Team Leader Allison Ingram 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

Oncology Practice Management ™

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

From The Editor A New Care Model on the Horizon.......................................................8

By Dawn Holcombe, MBA, FACMPE, ACHE

Features Payment Reform New Model Is Announced for Oncology Care.................................. 1 The World of Reimbursement Is Changing: Is Your Practice Ready?.......................................................................................1

By Jessica Turgon

ASCO Shares Concerns Regarding CMS Model................................ 6

By Rosemary Frei, MSc

Cancer Center Business Summit The Evolving Oncology Medical Home................................................ 1

By Dawn Holcombe, MBA, FACMPE, ACHE

Personalized Medicine and Future Delivery Systems.......................17

By Gail Thompson

Practice Management Cost-Effectiveness Analysis Shows Specialty Drugs Offer Value Despite High Cost................................................................................ 28

By Charles Bankhead

Continued on page 4

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.

March 2015

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Table of Contents March 2015 • Volume 5 • Number 2

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 registered 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 3

DEPARTMENTS Wealth Management Disability Insurance: Deciphering the COLA Rider........................ 29

By Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF

Clinical Trial Tracker Trials Under Way for Patients with Brain Cancer............................. 30 Drug Update Cyramza (Ramucirumab) Approved for the Treatment of Advanced Gastric Cancer and Metastatic Non–Small-Cell Lung Cancer.......................................................................................... 34

By Loretta Fala

Patient and Provider Access Transforming Medicare Payments: Ambitious New Goals........... 46

By Leah Ralph

Drug Coding FDA-Approved Medications Used for the Treatment of Multiple Myeloma................................................................................. 48

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

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Risë Marie Cleland President Oplinc, Inc Portland, OR Patrick A. Grusenmeyer, ScD, FACHE President Christiana Care Health Initiatives Newark, DE Teri U. Guidi, MBA, FAAMA President and CEO Oncology Management Consulting Group Pipersville, PA

Oncology Practice Management

Mariana Lamb, MS Executive Director Medical Oncology Association of Southern California Upland, CA

Robert D. Orzechowski, MBA, SPHR Chief Operating Officer Lancaster Cancer Center Lancaster, PA

Bonnie J. Miller, RN, BSN, OCN, FAAMA Administrative Director Women’s Cancer Center Fox Chase Cancer Center Philadelphia, PA

Nancy G. Payne, CMPE Executive Director Space Coast Cancer Center Titusville, FL

Karna W. Morrow, CPC, RCC, CCS-P, PCS Senior Consultant CSI Coding Strategies, Inc Powder Springs, GA

I March 2015

Sheryl A. Riley, RN, OCN, CMCN Director of Clinical Services SAI Systems Shelton, CT

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US-CELG140179

Payment Reform

New Model Is Announced for... Continued from the cover developed by the Centers for Medicare & Medicaid Services (CMS) Innovation Center, is to provide high-quality, well-coordinated, appropriately incentivized oncology care while controlling expenses and reducing costs, according to information provided by CMS. It also aligns with the US Department of Health & Human Services’ goal of moving toward provider payments that are based on quality of care, rather than quantity. It is estimated that more than 1.6 million people are diagnosed with cancer annually, the majority of which are at least 65 years old and Medicare beneficiaries.

“Based on feedback from the medical, consumer and business communities, we are launching this new model of care to support clinicians’ work with their patients,” Patrick Conway, MD, CMS chief medical officer and deputy administrator for innovation and quality, stated in a release announcing the new care model. “We aim to provide Medicare beneficiaries struggling with cancer with high-quality care around the clock and to reward doctors for the value, not volume, of care they provide. Improving the way we pay providers and deliver care to patients will result in healthier people.”

Through this model, CMS will provide qualifying providers with the $160 PBPM care management payment for each eligible beneficiary receiving chemotherapy and the care related to it. Payments will be made for the duration of a 6-month episode, hinged on the initiation of chemotherapy treatment. This payment will remain constant for OCM’s designated 5-year performance period. Eligible practices can be physician groups or solo practitioners who administer cancer chemotherapy and who are enrolled in Medicare. They must also meet the

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following requirements to participate in OCM and receive payment: • Provide core functions of patient navigation • Document a care plan that encompasses the Institute of Medicine Care Management Plan • Give patients around-the-clock access to an appropriate clinician who has real-time access to patient medical records • Treat patients according to nationally recognized clinical guidelines • Use data to drive quality improvement • Use electronic health records and attest to stage 2 of Meaningful Use by the third year of participation.

As part of their participation, prac-

Oncology Practice Management

tices must also report data quarterly to the CMS Innovation Center on eligible, participating beneficiaries. The Innovation Center will monitor participating practices to ensure that patients are accessing and receiving high-quality care, practices have the necessary infrastructure in place to deliver comprehensive care, and practices are submitting required data.

Monitoring by the Innovation Center may include site visits, tracking and analysis of data, patient surveys, and medical record audits.

Payments may be billed to Medicare for the entire 6-month chemotherapy episode, whether or not the patient receives chemotherapy treatment for the full 6 months; payments

ASCO Shares Concerns Regarding CMS Model

By Rosemary Frei, MSc

T

he announcement in February of a new Oncology Care Model has brought a lukewarm response by the American Society of Clinical Oncology (ASCO). Developed by the Centers for Medicare & Medicaid Services (CMS) Innovation Center and announced through the US Department of Health & Human Services, the new care delivery model encompasses a multipayer structure as well as incentivized and monthly per beneficiary payments to participating practices (see article on this page).

In August 2014, the Innovation Center, known officially as the Center for Medicare & Medicaid Innovation (CMMI) posted and sought comments online for the proposed model, titled “Preliminary Design for an Oncology-­

I March 2015

Focused Model.” The new model was announced February 12, 2015.

That same day ASCO issued a news release outlining what its officials see as challenges with the new model. ASCO Chief Medical Officer Richard L. Schilsky, MD, FACP, FASCO, echoed these concerns when reached by Oncology Practice Management.

“While CMS is to be commended for seeking new approaches to payment, we are disappointed they have chosen to pursue only one model—and one that continues to rely on a broken fee-for-service system,” Dr Schilsky stated in an e-mail to the journal. “ASCO looks forward to working with both public and private payers to explore new payment strategies that better reflect modern oncology practice and support high-val-

Payment Reform

cannot be billed to Medicare once the patient enters hospice. After an episode ends, another 6-month episode may be started if chemotherapy

cology practices and payers, and CMS is asking for nonbinding letters of intent to gauge interest, due April 9 for payers and May 7 for

other payers, including commercial insurers, state Medicaid agencies, and other government payers. The agency will publicly post a list of payers who have submitted letters of intent and agreed to the posting; the agency will also post a list of practices, based on the same conditions. Payers and practices will then have an opportunity to discuss and coordinate collaboration within the OCM. Provider applications will be evaluated using a process that favors those who are partnering with approved payers. They will be notified of their selection status within 6 months from the time they submit their application. l

“We aim to provide Medicare beneficiaries struggling with cancer with high-quality care around the clock and to reward doctors for the value, not volume, of care they provide.”

—Patrick Conway, MD, Centers for Medicare & Medicaid Services

treatment is still active and being billed. Management of patients who are not receiving chemotherapy will not be eligible for this model.

The program is voluntary for on-

practices. Those who submit completed, timely letters of intent will be eligible to submit final applications (due June 18). CMS is also encouraging participation from

ue, patient-centered care.”

During the period for comments on the proposal, ASCO Chief Executive Officer Allen S. Lichter, MD, FASCO, submitted a letter to CMS detailing the organization’s concerns with the proposal. He took issue with most aspects of it.

With respect to the calculation of performance-based payments, Dr Lichter wrote that, “CMMI should provide a transition period where it does not calculate and retain a discount on the target cost of per­ formance period episodes,” and “CMMI should defer implementing any hold-back retained by Medicare until after the first 2 performance periods are completed.”

He noted, in addition, that ASCO has been developing its Consolidated Payments for Oncology Care (CPOC) model. He concluded that CPOC, which ASCO released in May 2014, “shares a number of important policy goals with the [Oncology Care Model] framework, and our model is designed to provide Medicare and other payers with the

flexibility to incorporate its key components into a variety of reform approaches. We would very much like to work with you to explore ways that we can leverage our respective efforts to build a better payment system in oncology.”

ment regarding ASCO’s concerns.

The Oncology Care Model developed through CMMI offers eligible practitioners a $160 per-beneficiary, per-month payment for a 6-month episode of chemotherapy care, as well as the potential for an incentivized, performance-based payment for care episodes. Participating practices must adhere to specified guidelines and requirements, and demonstrate the capabilities to provide and document care as outlined in the Oncology Care Model (OCM) Request for Applications (RFA) February 2015.

CMS is also soliciting participation from other payers, including commercial insurers, state agencies, and government payers.

For more information, interested practices can download the application from http://innovation.cms. gov/Files/x/ocmrfa.pdf. Practices that are interested in participating are required to submit a nonbinding letter of intent by May 7; interested payers must submit letters of intent by April 9. l

“While CMS is to be commended for seeking new approaches to payment, we are disappointed they have chosen to pursue only one model—and one that continues to rely on a broken fee-forservice system.”

—Richard L. Schilsky, MD, FACP, FASCO

CMS declined Oncology Practice Management’s requests for com-

March 2015

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From the Editor

A New Care Model on the Horizon

By Dawn Holcombe, MBA, FACMPE, ACHE; President, DGH Consulting, South Windsor, CT; Editor-in-Chief, Oncology Practice Management

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ur inboxes are overflowing with news of the Oncology Care Model (OCM) that was announced by the US Department of Health & Human Services on February 12. Full details are being unveiled regarding this bundled payment model, which was developed by the Centers for Medicare & Medicaid Services (CMS) Innovation Center, and practices are starting to assess the expectations of the program versus the risks and rewards of participation or a decision not to participate.

According to available program details, participating providers will receive a per-beneficiary, per-month (PBPM) care management payment of $160 for 6 months for each beneficiary receiving chemotherapy, hinged on the initiation of treatment; they will also be eligible to receive performance-based payments. Participating providers are expected to be available and have access to patient medical records on a 24-hour basis to manage common therapy complications in the hopes of avoiding hospitalizations or emergency department visits.

Another important element of this program calls for CMS to consider support and participation from other payers. Payers are encouraged to submit letters of intent to participate earlier than practices so that practices may review potential partnerships in their markets. The scoring and evaluation process that CMS will use to accept final participants is weighted heavily toward participants who are partnering with other payers in this program.

It will be important for practices considering participation to read the fine print surrounding this model.

The application is quite detailed and requires projection of volume, a list-

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ing of beneficiaries, and attestation of ability to perform on specified measures. Practices will have to create and submit a full implementation plan for the first 2 years of the program, including current and future timelines for implementation of program processes.

Electronic practice support will be critical. Practices must be compliant with stage 2 of Meaningful Use by the end of the third performance year and have electronic support for the documentation and reporting that is part and parcel of this program. Documenting a care plan for each patient that encompasses all elements of the required 13 components of the Institute of Medicine Care Management Plan and the 10 elements of the National Cancer Institute Sample Patient Navigation activities have the potential to stretch the limits of practice systems.

The OCM has been in development for years, with input from many sources, including those in the oncology community. It will be interesting to see if the model that has been unveiled will attract significant participation. Is the $160 PBPM payment sufficient to cover the costs of participation and patient care? Are the reporting and compliance expectations compatible with current or near-fu-

Oncology Practice Management

I March 2015

ture capabilities of oncology practices? Submitting a letter of intent may be easy by April 9 for payers or May 7 for practices, but is the time frame of June 18, 2015, feasible for the projections and relationships expected for a full application? Will this model be the first step in standardizing oncology payer relationships? Or will it be a voluntary program that fails to attract participants?

Time will answer these questions.

For now, practices should carefully review the program, application, and participation details for themselves.

Are these expectations achievable? It is interesting that only physicians may participate in this model, and that much of the expected savings will likely come from hospital services and treatment regimen choices. This is more of a bottom-up approach to finding savings than the accountable care model, which often has been housed in larger institutions.

Drug costs are included in these totals, including those billed through Medicare Part A, Part B, or Part D. Much of our cancer care pharmacy costs are found in combination regimens, and many new drugs themselves layer on top of existing regimens. Moving to episode-based, total cost-of-care bundles with incentives for savings will encourage greater attention to the total costs of care, but will it lead to restricted access to new treatments and options for Medicare beneficiaries?

The devil will be in the details of this program (ie, how it is written and executed), as well as the capability of our medical system to accept these terms. It will be interesting to watch the reactions to this program unfold in the next few weeks, as practices continue their research into and understanding of this new model. l

ACCC: MEETING YOUR NEEDS Gear up for a full menu of meetings with need-to-know information for the entire cancer care team. Don’t miss out on unparalleled opportunities to advance your learning in critical areas, and earn CE credits. Be sure to share this information with your colleagues who can benefit from these events.

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Any member of the cancer care team who deals with oncology business and reimbursement will benefit from these FREE one-day meetings. Gain a fullspectrum perspective with sessions on payment reform; the latest trends in coding and billing; proper management of financial data; and the practical application of radiation oncology CPT codes.

Tuesday, May 5, 2015 Tampa, Florida

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ONCOLOGY PHARMACY EDUCATION NETWORK REGIONAL MEETINGS

Tuesday, August 25, 2015 Indianapolis, Indiana

Tuesday, November 17, 2015 Boston, Massachusetts

These two-day meetings provide take-away tools and information to oncology pharmacists and members of the cancer care team in pharmacy operations.

Thursday, December 10, 2015 Birmingham, Alabama

May 15–16, 2015 New Brunswick, New Jersey

June 26–27, 2015

32ND NATIONAL ONCOLOGY CONFERENCE

Fort Lauderdale, Florida

July 10–11, 2015 Charlotte, North Carolina

Stay Tuned!

The ACCC National Oncology Conference delivers innovative ideas, solutions, and strategies to implement in your cancer program.

October 21–24, 2015 Portland Marriott Downtown Waterfront Portland, Oregon

For details on all ACCC meetings go to www.accc-cancer.org/meetings

Payment Reform

The World of Reimbursement Is Changing... Continued from the cover Figure 1 T he Triple Aim of Healthcare Reform Efficiency

Triple aim

Cost

Quality

and error. To date, many reform activities have targeted operational processes and practices as indicators of quality. In certain markets, payers have started to partner with providers to experiment with sharing the risk of patient care costs. Unlike the larger patient panels in primary care settings, cancer care is challenged by smaller patient cohorts with increased risk from cost variability.

Many of the early cancer reimbursement pilots have evaluated different measures to account for the complexity and corresponding risk in cancer care.

Just recently, the US Department of Health & Human Services announced a new Oncology Care Model, applicable to beneficiaries who are undergoing chemotherapeutic regimens.2 This per-beneficiary, permonth payment model, with potential incentive payments for demonstrated cost-savings, is the latest example of the transition toward reimbursement models that focus on value.

From an oncologist’s point of view, the patient care, operational, and financial implications will need to be understood before any new reimbursement model is tried in daily practice. Certain practice characteristics, such as information technology (IT) system functionality or the local

payer mix, can determine the success a practice may have utilizing one or all of these methodologies.

the United States have focused on one or more of the methodologies noted above. Each initiative seeks to test certain interventions and deterPayment Reform Overview mine the impact on the cost of canThroughout the United States, cer care. Given this environment, it payers and oncology providers are is important to ask whether your collaborating on 4 types of value-­ practice or center is ready to assume based reimbursement models: the challenges and responsibilities of • Pay for performance: perfor- participating in an alternative paymance-based payments related to ment model. To help you answer the oncologists’ compliance with that question, each model and releselect clinical pathways and evi- vant examples are discussed below. dence-based protocols • Oncology medical home (OMH): Pay for Performance Pay for performance rewards the coordinated payments for care management across a spectrum of quality of care through payment inclinical and supportive-care services centives for value, with value broadly defined as a function of quality, efficiency, safety, and cost. This incentive-based approach usually proThe full transition to duces results on select measures, but it may not address all areas that a value-based payer, employer, patient, or healthreimbursement will likely care delivery system would like to be one of trial and error. monitor. In oncology, payers typically reward providers who adhere to To date, many reform evidence-based protocols and cliniactivities have targeted cal pathways.

The Innovent Oncology program operational processes (supported by McKesson Specialty and practices as Health and US Oncology Inc), Texas Oncology, and Aetna exindicators of quality. plored an oncology payment model that highlighted the importance of evidence-based protocols.3-5 These • Bundled payments: episodic care organizations sought to change cerpayments designed to drive inte- tain cost drivers within cancer care, gration, quality, and efficiency specifically the variable use of drugs, through shared incentives and the deterioration of patient health between treatments, and patient acaccountability • Shared savings programs: targeted ceptance of interventions near the emergency department visit and end of life.3-5 The 2-year pilot project hospital utilization cost reductions focused on the following5: through adherence to clinical • Provider use of evidence-based clinical pathways and health IT pathways and guidelines, with costsavings to the payer and shared • Patient support services with the oncologists through re- • Advance care planning (ACP).

Aetna incentivized provider adduced use of services and improved herence to the evidence-based care management.

Certain pilots and initiatives in guidelines and ACP. Health IT sysContinued on page 12

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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.

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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.

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Payment Reform

The World of Reimbursement Is Changing...Continued from page 10 Figure 2 A Medical Home Environment

Nurses Home health

Care managers

Other (residents)

NPPs

Oncologist

Social workers

Community volunteers Patient navigator

NPP indicates nonphysician provider.

tems supported physician access to and use of the guidelines and allowed for information sharing and performance monitoring across the group. Oncology nurses worked with the practices and the Aetna care management team to help patients manage treatment symptoms and side effects. Finally, patients were offered access to end-of-life planning throughout their care. The results included improved pathway adherence from participating providers. In a recent article on the outcomes of this pilot, cost reductions from a decline in emergency department visits, hospital admissions, and the number of hospital days were more than $500,000 for the 221 pilot members.5 As a pilot, the Aetna example was successful in demonstrating the value of incentivizing performance, with performance defined as pathway adherence. The challenge to an oncology provider is that, historically, limited incentives have been linked to pay-for-performance methodologies.

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To fully evolve from a fee-for-service model, pay-for-performance initiatives will need to be included with other value-based reimbursement models.

Oncology Medical Home An OMH is designed to improve quality and reduce the waste that results from poorly coordinated care.

The transition to a medical home

Oncology Practice Management

model in primary care practices generally reorients the care model from a single provider to a coordinated team that shares information among clinicians and specialists (Figure 2).

This concept is not new to cancer care practices, and cancer centers typically organize care in a patient-centric manner, which includes patients and their families or other caregivers in planning care and managing conditions. The National Committee for Quality Assurance (NCQA) certifies primary care and specialty practices that meet the organization’s requirements for focusing on the patient and coordinating care.6 A notable pilot is the COME HOME project,7 in which several community oncology practices are participating. In addition to that initiative, Consultants in Medical Oncology and Hematology, PC, a 9-physician medical-oncology practice, reengineered its care delivery processes and became the first NCQA­-recognized level 3 Oncology Patient-Centered Medical Home (PCMH). For payers and providers, the aims of a PCMH program are enhanced adherence to evidence­ based protocols and a targeted reduction in the total cost of care.

KEY POINTS ➤W ith more individuals living with cancer as a chronic disease, cancer care expenditures are expected to grow from $125 billion in 2010 to more than $170 billion in 2020 ➤P ay for performance rewards the quality of care through payment incentives for value, with value broadly defined as a function of quality, efficiency, safety, and cost ➤T he concept of a medical home is not new to cancer care practices, and cancer centers typically organize care in a patient-centric manner ➤T he primary goal of bundled payments is to restructure financial incentives for conditions with a clear beginning and end. This model can be challenging because of the complexity of cancer care ➤C ommercial payers continue to work with oncology groups to pilot a range of shared savings initiatives that could change the economics of practices

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Payment Reform

Some PCMH models may include provisions for sharing savings between payers and providers that are achieved from better disease management. Others may embed upfront payment in the form of a care coordination or patient navigation fee or similar compensation to support additional resources for more comprehensive patient support. This fee, or per-member per-month (PMPM) payment, needs to be evaluated to project the incremental revenues and expenses to the practice or center. In many of the oncology projects, grant dollars were also included to support the additional expense within the practices. As these projects continue to gain traction with commercial payers, the PMPM payment will need to effectively compensate practices for these additional expenses and the evolution away from fee-for-service economics.

Bundled Payments Bundled payments, also known as episode payments, encompass only certain services (eg, hospital inpatient and select physician services) or a part of the care continuum. In these bundled arrangements, a healthcare provider is given a lump sum that covers those specific healthcare services related to a specific diagnosis or procedure. The primary goal of bundling is to restructure financial incentives; these payments have generally been applied to conditions with a clear beginning and end.

UnitedHealthcare has piloted episode payments in the outpatient oncology setting to separate practice income from drug sales. The initiative was effective in reducing costs associated with certain medications, and established an environment of performance measurement and improvement. Recently, this payer signed a fixed payment agreement with The University of Texas MD Anderson Cancer Center for patients with a specific type of head

and neck cancer.8 Several other initiatives with different payers have targeted specific modalities such as radiation oncology. Overall, bundled payments for a patient’s total cycle of treatment—and not the number of visits or the amount of chemotherapy given—may be conducive to patient-centric, evidence-based care that does not introduce conflicting revenue incentives for physicians.

Recently, more discussion in the oncology community has targeted radiation therapy as the better treatment modality for bundled payments.

Again, select pilots have been engaged across the country, with several larger radiation oncology practices promoting the benefits of bundled payments. This area will likely be one of continued interest as access to data, shared results, and community-based health information exchanges allow for the tracking of patients under this type of methodology.

Shared Savings Programs When providers and health systems typically discuss shared savings initiatives, they usually involve accountable care organization participation under the Centers for Medicare & Medicaid Services’ Medicare Shared Savings Program (SSP).9 The focus of SSPs has not been cancer care; rather, high-volume chronic conditions, such as diabetes, asthma, heart disease, and chronic obstructive pulmonary disease, have been targeted. In light of the increasing costs of cancer care, commercial payers are working with oncology groups to pilot a range of shared savings initiatives that could change the economics of practices.

As an example, Priority Health, a regional, Michigan-based insurance carrier, spearheaded a 2-year OMH program in February 2011. Developed and implemented in collaboration with community oncology practices, the program currently encompasses more than 60 physicians in 6 practices and exemplifies the core elements of payment reform, care redesign, and performance measurement.10 First, the practices agreed to adopt the key elements of an OMH model: adherence to clinical pathways; enhanced patient education, engagement, and triage initiatives; ACP; and survivorship planning. As part of the agreement, the practices and

Jessica Turgon

The primary goal of bundling is to restructure financial incentives; these payments have generally been applied to conditions with a clear beginning and end.

Despite these efforts, it is impor­ tant to note that bundled payments in oncology often can be difficult because of the complexity of cancer care; the various modalities, treatments, specialties, and sites of care make it difficult to define qualified patients for a specific episode of care.

This complexity also impacts the payment allocation, requiring rigor in measuring, monitoring, and rewarding individual providers for quality and outcomes.

Continued on page 14

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Payment Reform

The World of Reimbursement Is Changing... Continued from page 13 Priority Health adopted performance metrics to assess patient experience, health outcomes, and per capita utilization. Early results included a decrease in emergency department utilization and a reduction in the total cost of care.

To align reimbursement with these value-based initiatives, Priority Health agreed to the following payment mechanisms: • A monthly chemotherapy management fee • Enhanced drug acquisition costs • An annual infrastructure payment • Enhanced fees for ACP, treatment planning, genetic counseling, and other agreed-on services • Shared savings for reductions in emergency department visits and admissions.

Working with the practices, the payer recognized that to sustain change, several payment mechanisms were needed to achieve the agreed-on patient care goals in the most cost-effective manner.

Key Takeaways Although there has been longstanding discussion about new models for healthcare delivery and payment reform, the conversation in oncology has rapidly turned to questions of “when” and “how,” rather than “if.”

Simply acknowledging the evolving landscape will do little to help oncology providers in preparing and positioning themselves for the transitions ahead. Results from early programs have shown that the application of 1 or more of these reimbursement models has made an impact on the costs of delivering care to patients with cancer. Oncology practices will need to consider these new arrangements as well as the implications to their practices and patients. l References

1. Mariotto AB, Yabroff KR, Shao Y, et al. Projections of the cost of cancer care in the United States: 20102020. J Natl Cancer Inst. 2011;103:117-128. Erratum in: J Natl Cancer Inst. 2011;103:699.

2. Centers for Medicare & Medicaid Services. Oncolo-

gy Care Model. http://innovation.cms.gov/initiatives/ Oncology-Care/. Accessed March 6, 2015.

3. McKesson Specialty Health-Innovent Oncology.

Connecting payers and physicians for improved patient care. www.innoventoncology.com/web. Accessed March 6, 2015.

4. McKesson Specialty Health-Innovent Oncology.

Aetna and US Oncology team up to improve quality, cost of cancer care. www.innoventoncology.com/ web/1AboutInnoventOncology/2News_Updates_ Archives/870C7B000C6B3855E0440003BADBF04B. Accessed March 6, 2015.

5. Hoverman JR, Klein I, Harrison DW, et al. Opening the black box: the impact of an oncology management program consisting of level I pathways and an outbound nurse call system. J Oncol Pract. 2014;10:63-67.

6. National Committee for Quality Assurance. Patient-centered specialty practice: excellence in care coordination, recognized. www.ncqa.org/Portals/0/ Programs/Recognition/PCSP/PCSP_brochure.pdf. Accessed March 6, 2015.

7. COME HOME: Innovative Oncology Business Solutions, Inc. The COME HOME model. www.come homeprogram.com/index.php/come-home-practices/.

Accessed March 6, 2015.

8. The University of Texas MD Anderson Cancer Center. MD Anderson, UnitedHealthcare launch new cancer care payment model. www.mdanderson.org/ newsroom/news-releases/2014/md-anderson-unitedhealthcare-new-cancer-payment.html. Accessed March 6, 2015.

9. Centers for Medicare & Medicaid Services. Shared Savings Program. www.cms.gov/Medicare/MedicareFee-for-Service-Payment/sharedsavingsprogram/ index.html?redirect=/SharedSavingsProgram/. Accessed March 6, 2015.

10. Fox J. Lessons from an oncology medical home collaborative. Am J Managed Care. 2013;19:SP5-SP9.

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Cancer Center Business Summit

The Evolving Oncology Medical Home Continued from the cover Led by Ira M. Klein, MD, MBA, FACP, National Medical Director, Clinical Thought Leadership, Office of the Chief Medical Officer, Aetna, and Michael Kolodziej, MD, National Medical Director, Oncology Solutions, Aetna, the panel also featured Maria Sipala, Director, Strategic Planning, and Amy Supraner, Strategic Planning Manager, both from National Network Contracting, Aetna. Barry Russo, MBA, CEO, The Center for Cancer and Blood Disorders, and Kathleen G. Lokay, President and CEO, Via Oncology, rounded out the panel.

Pathways are often discussed as potential solutions for oncology management, but the panelists emphasized that pathways are simply a minor tool in a larger toolkit being developed for evolving programs and payer–provider relationships. Drs Klein and Kolodziej indicated that Aetna has had success with several options that were piloted in recent years among a diverse group of practices. This may be in part, they noted, because Aetna has national reach but generally does not hold the highest share in any given market, which helps to keep the volume of patients in these pilots manageable for Aetna and participating practices.

Aetna has examined and experi-

mented with external vendors of pathways and oncology management, but is now taking an agnostic approach to pathways, the team noted: as long as an oncology prac-

Pathways are often discussed as potential solutions for oncology management, but the panelists emphasized that pathways are simply a minor tool in a larger toolkit. tice is satisfied with a formal, evidence-based, documentable electronic pathways program, Aetna is not going to push a vendor of its own choosing on the practice. It was noted, however, that Via Oncology currently provides a pathways solution to 10 of the 13 practices in formal quality programs with Aetna.

Consistency, accountability, responsibility, and flexibility are outputs that Aetna seeks from partnering physician groups, and it does not want to overthink practice drug

KEY POINTS ➤ Consistency, accountability, responsibility, and flexibility are sought-after outputs from partnering physician groups ➤ Aetna is working on a general, OMH-type model that relies on formal, evidence-based decision-making documentation and reporting capabilities, as well as a commitment by participating practices to patient-focused initiatives ➤ There is generally a baseline patient volume to make pilot programs work; this may be anywhere from 75,000 to 100,000 covered lives in a market ➤ Pathways have a role for compliance and adherence, and practices that do not use a formal, electronic pathway program often believe they are treating on pathway, but they usually are not

choices or overmanage treatment choices, according to Drs Klein and Kolodziej. However, practices will be penalized in the near future if those choices do not prove to be responsible. The practices currently working with Aetna have changed their culture and practice perspectives to be substantially more patient-focused, which may also change what practices come to expect from the products they use and what they look for from the pharmaceutical industry.

The company continues to work on a general OMH-type model that relies on formal evidence-based decision-making documentation and reporting capabilities. It also entails a commitment by participating practices to patient-focused initiatives, including management of hospitalizations and emergency department visits through attentive triage and patient management, pain management, formal care plans and advance care planning, and a commitment between practices and Aetna to collaboratively review the scope and costs of care.

In addition to discussing OMHbased initiatives, panelists also participated in an active question-­ and-answer session. One audience member questioned whether Aetna has had to contend with simultaneous OMH and accountable care organization (ACO) models within the same practice. The Aetna team responded that yes, this has occurred, and it is challenging.

The ACO model is more focused on primary care and has a high-volume, low-cost attribution, whereas the OMH model is the opposite: low volume, but high cost. ACOs in the future will likely benefit from partnering with subspecialists who can manage these sickest patients most effectively, the Aetna team indicated; however, the issue of how to involve specialists or how best to Continued on page 18

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Cancer Center Business Summit

Personalized Medicine and Future Delivery Systems

By Gail Thompson

A

panel of experts gathered recently to explore changes that are expected for oncology in the field of personalized medicine as well as their impact on future delivery systems. The panel discussion, held in November at the Cancer Center Business Summit, highlighted what appears to be a gap between the medical community and companies that provide testing for personalized medicine. At the same time, the panelists agreed that available data and information relating personalized medicine to cancer treatment choices is not yet being used to full efficacy, which presents an untapped opportunity for cancer patients.

Moderated by Edward Abrahams, PhD, President, Personalized Medicine Coalition, the panel included Maurie Markman, MD, Senior Vice President for Clinical Affairs, Cancer Treatment Centers of America; Catherine A. McCarty, PhD, MPH, Principal Research Scientist, Essentia Health; Timothy Thompson, CEO, Intervention Insights; David Nixon, CEO, InformedDNA; and Christine Cournoyer, CEO, N-of-One. The panelists presented their own perspectives and debated several questions, including the following: Who will become the interpreter of evidence as well as the arbiter of acceptable or covered treatments? Will personalized testing on a large scale be allowed or required, and at what thresholds for pricing? Will physicians change their treatment choices based upon the results of these tests?

When do the tests change the dynamic of the oncologist–patient interaction? Will cancer care reach a point where personalized testing, rather than the oncologist, drives

and determines approved therapies?

Other points that were raised included the following: Will pharmaceutical manufacturers move away from a payer coverage–physician acceptance paradigm for therapies in favor of identifying specific biomarkers and determining how arbiters interpret results and value? Does the speed at which personalized markers and tests are evolving impact the definition of “evidence” within evidence-based care choices? Are changes occurring so rapidly that most stakeholders will not be able to keep up?

about how to bring discoveries in cancer testing and therapy into rural healthcare. She described Essentia Health as the second largest healthcare delivery system in rural America, as well as a growing accountable care organization. She mentioned that as a member of the HMO Research Network—a consortium of provider and HMO organizations that have well-established research capabilities—Essentia Health is generating extensive amounts of data.

The current challenge for the HMO Research Network is to build decision support tools and resources for physicians from the data, and to develop models to apply that data at the patient level.

Mr Thompson, as a representative of the organizations that provide personalized medicine testing, dem­ onstrated how his team uses evidence and testing results to help physicians decide what treatments are appropriate to use with specific patients. Mr Nixon of Informed DNA commented that his team delivers both genetic testing counseling and decision support for patients and providers. He suggested that the majority of oncologists and surgeons who order genetic testing do not understand the implications and findings, and are not equipped to interpret them for patients or to assist with making treatment choices based on them. Mr Nixon noted that genetics professionals deserve a place in the physician decision process, and suggested that a key step to ensure the involvement of the counselors is for payers to require genetics services counseling.

Ms Cournoyer commented on the challenges that physicians and patients face, indicating that broader

The question is not when data within this field will become available, but rather how to sift through existing data to determine what is important and actionable.

During the discussion, Dr Markman identified precision medicine as the future of healthcare. The question, he stated, is not when data within this field will become available (much of it is available already), but rather how to sift through existing data to determine what is important and actionable. He suggested that the challenge will be in shifting the relevance of treatment from individual patients to groups of patients, and that a national registry of results might be one useful solution.

Dr McCarty shared her concerns

Continued on page 18

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Cancer Center Business Summit

The Evolving Oncology Medical Home Continued from page 16 allocate or share funds has not yet been addressed.

Another question addressed whether Aetna’s emerging OMH model was also being applied in the hospital setting, particularly since the majority of care in many states is now hospital-based. Aetna has seen some interest in its current model, the team noted, but also a lack of interest from hospital systems that are doing well under the systems they have in place. This often leads to arrangements with innovation and flexibility within community practices, which is good for patients and the community.

The Aetna team suggested that there is generally a baseline patient volume to make pilot programs work: approximately 75,000 to 100,000 covered lives in a market might make sense. The number of patients with breast, lung, and colon cancer seems to normalize and make sense when practices see more than 50 patients, and 100 patients covered through Aetna becomes a substantial enough volume to start looking at partnerships; this number might be fewer in the Medicare population.

The OMH model being used by Aetna and its participating practices is still a transitional model, and the concept of shared savings has its own unique issues, the Aetna team noted.

Exploration of shared savings potential allows payers to benchmark the size of an opportunity and perhaps the size of an eventual management payment. Current programs and pilots allow both Aetna and participat-

Some practices will rise to the challenge and manage care in a manner that meets the needs of the patient, the payer, and the practice, and others may struggle. ing practices to better understand the cost structure of oncology treatment and care. They are also now looking at cost variation by common disease, biological determinants, and other variables.

Mr Russo and the Aetna team stressed the value of their relationship is not limited to the financial elements of shared savings and management; rather, they are both developing an understanding of how to implement pilots at safe, reasonable volume levels. Aetna

encourages its partner practices to explore similar programs, even based upon the Aetna model, with other payers, in the hopes of shortening the learning curve and simultaneously raising the bar for oncology management consistently across a given market.

At the conclusion of the session, the Aetna team presented its view of the future of oncology management: pathways have a role for compliance and adherence, and practices that do not use a formal, electronic pathway program often believe they are treating on pathway, but they usually are not. With a clinical decision support tool that the practices choose and trust, compliance rises, which facilitates the development of a solid process and, from that, a reasonable management fee.

A reasonable management fee may in the future lead to reduced reliance on pathway performance and compliance reporting; however, there will be winners and losers. Some practices will rise to the challenge and manage care in a manner that meets the needs of the patient, the payer, and the practice, and others may struggle, and then struggle further if they cannot perform at a level to justify a higher management fee. The first step is with pathways and the general concept of an OMH. l

Personalized Medicine and Future... Continued from page 17 testing and guided therapy may provide alternatives to patients who are failing standard-of-care therapy. In addition, she noted that better integration of molecular testing has the potential to transform personalized cancer care. Ms Cournoyer shared that her company, N-of-One, has

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developed a partnership with Utahbased Intermountain Healthcare to offer personalized molecular testing and counseling to patients and bring the results to Intermountain Healthcare tumor boards for discussion.

The general consensus among panelists was that the role of external

Oncology Practice Management

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companies that provide testing and offer counseling and guidance to both physicians and patients is growing and will continue to expand as personalized medicine evolves. This may have a significant impact on clinicians, pharmaceutical manufacturers, and patients with cancer. l

In mCRPC therapy…

Is there more to the story?

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.

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.

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.

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.

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. mCRPC=metastatic castration-resistant prostate cancer; AST=aspartate aminotransferase; ALT=alanine aminotransferase.

Please see additional Important Safety Information on the next page.

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

For men with mCRPC who progressed on ADT

In a clinical trial, patients had a median overall survival on ZYTIGA® (abiraterone acetate) of…*

More than 1,000 days.

And every day tells a story.

35.3 IMPROVEMENT IN MEDIAN OVERALL SURVIVAL 5.2 MONTHS compared with placebo plus prednisone.

MONTHS MEDIAN OVERALL SURVIVAL FOR ZYTIGA® plus prednisone† vs 30.1 MONTHS with placebo plus prednisone (active compound).‡

Co-primary end point—overall survival: hazard ratio (HR)=0.792; 95% CI: 0.655, 0.956; P=0.0151; prespecified value for statistical significance not reached.

Co-primary end point—radiographic progression-free survival: median not reached for ZYTIGA® plus prednisone vs a median of 8.28 months for placebo plus prednisone. HR=0.425; 95% CI: 0.347, 0.522; P<0.0001.

IMPORTANT SAFETY INFORMATION (cont) 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.

Hepatotoxicity—Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). 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.

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. *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 overall survival (OS) and radiographic progression-free survival.

ADT=androgen-deprivation therapy.

Janssen Biotech, Inc. © Janssen Biotech, Inc. 2014 6/14 016819-140612

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

B:11.125 in

003307-130924

S:10.375 in

T:10.875 in

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 enzyme CYP2D6. 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 vitro, ZYTIGA® inhibits CYP2C8. There are no clinical data on the use of ZYTIGA® with drugs that are substrates of CYP2C8. Patients should be monitored closely for signs of toxicity related to the CYP2C8 substrate if used concomitantly with abiraterone acetate.

Use in Specific Populations—Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C). †At a prespecified interim analysis for OS, 37% (200/546) of patients treated with ZYTIGA® plus prednisone compared with 43% (234/542) of patients treated with placebo plus prednisone had died. ‡Prednisone, as a single agent, is not approved for the treatment of prostate cancer.

Learn more today at

www.zytigahcp.com.

Every day tells a story.

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 ≥2.5X ULN 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) System/Organ Class All Grades1 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 discomfort7 3.8 0.5 2.8 0 Cardiac failure8 2.3 1.9 1.0 0.3

ZYTIGA® (abiraterone acetate) Tablets

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) System/Organ Class All Grades1 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.

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 enzyme CYP2D6. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

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 vitro, ZYTIGA inhibits CYP2C8. There are no clinical data on the use of ZYTIGA with drugs that are substrates of CYP2C8. However, patients should be monitored closely for signs of toxicity related to the CYP2C8 substrate if used concomitantly with abiraterone acetate.

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].

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.

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Manufactured for: Janssen Biotech, Inc. Horsham, PA 19044 © Janssen Biotech, Inc. 2012 Revised: May 2014 015924-140528

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Before prescribing ZYTIGA® (abiraterone acetate), please see the accompanying full Prescribing Information including DOSAGE and ADMINISTRATION, WARNINGS and PRECAUTIONS. Navigator™ is a registered trademark of Engage Healthcare Communications, LLC, an affiliate of The Lynx Group. No part of these materials may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher.

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Practice Management

Cost-Effectiveness Analysis Shows Specialty Drugs Offer Value Despite High Cost

By Charles Bankhead

D

espite substantially higher costs, specialty drugs can offer value comparable with that of traditional medications under certain circumstances, according to a recent cost-effectiveness analysis covering 12 years of FDA drug approvals (Chambers JD, et al. Health Aff [Millwood]. 2014;33:1751-1760).

Specialty drugs, many of which are cancer drugs, offered larger health gains and improved survival but at an average cost per quality-adjusted life-year (QALY) of more than 15 times greater than the traditional drugs in the same class.

Three times as many specialty drugs had a cost per QALY in excess of $150,000. Even so, the overall cost-effectiveness was comparable for specialty and traditional drugs.

“Payers have not yet found the formula for managing specialty drugs,” concluded the investigators, led by James D. Chambers, PhD, MPharm, MSc, Assistant Professor at Tufts Medical Center Institute for Clinical Research and Health Policy Studies, Boston. “Insurers should continue to experiment with a combination of existing formulary management tools and novel strategies to maximize patient access to specialty drugs while minimizing their cost.”

In recent years, many of the drugs approved by the FDA are classified as specialty or “large-molecule” agents.

Specialty drugs have represented therapeutic advances for a variety of conditions, especially in cancer. However, the high cost of these medications has attracted considerable attention.

Dr Chambers and colleagues evaluated FDA drug approvals of new molecular entities (NMEs) from 1999 to 2011. They focused on incremental health improvements and

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James D. Chambers, PhD, MPharm, MSc

incremental costs associated with specialty drugs after their introduction to the marketplace.

The team calculated QALYs for each agent to determine incremental health benefit. Incremental cost was derived from the difference in cost between the specialty drugs and the existing treatment options. Incremental costs included direct drug costs and related costs (hospitalization and other health resource utilization).

Drugs were classified as specialty or traditional on the basis of inclusion (or exclusion) on the specialty drug lists of CVS Caremark and Express Scripts.

Dr Chambers and colleagues identified 279 NMEs approved by the FDA during the study period. Overall, 154 (55.2%) of the approvals involved specialty drugs.

The illness categories represented by the drugs included 25 for cancer (22 specialty drugs), 16 for infectious disease (12 specialty drugs), 14 for circulatory disease (4 specialty drugs), 11 for endocrine disease (2 specialty drugs), 11 for musculoskeletal and rheumatologic conditions (8 specialty drugs), and 10 for neuropsychiatric and neurologic conditions (1 specialty drug).

Quality and Cost The median incremental QALY

Oncology Practice Management

I March 2015

gain across all 102 drugs was 0.031, equivalent to 1.5 weeks of quality-adjusted survival gain. The mean QALY gain was 0.17.

Specialty drugs had a median QALY gain of 0.183 versus 0.002 for traditional drugs (P <.01) and mean gains of 0.25 and 0.08, respectively.

Approximately 33% of the drugs (15 specialty and 17 traditional drugs) were less effective or no more effective than the existing care. In addition, 14 specialty drugs and 2 traditional drugs were associated with ≥0.5 QALYs gained, or 6 months of quality-adjusted life expectancy.

For all 102 drugs included in the analysis, the median additional cost over existing care was $2950, with a mean of $42,561.

Specialty drugs were associated with a median additional cost of $12,238 compared with $784 for traditional drugs. The mean values were $72,917 and $3237, respectively.

Specialty drugs accounted for 13 of the leading 15 drugs in QALY gains and all 15 of the drugs associated with the largest additional costs. Furthermore, 26% of specialty drugs versus 9% of traditional drugs exceeded a cost per QALY gained of $150,000.

“Our study suggests that many new specialty and traditional drugs offer relatively modest benefits over preexisting care,” the researchers wrote.

“Many of the drugs that have offered the largest clinical advancements have been specialty drugs,” they added. “However, the incremental costs for specialty drugs have exceeded the incremental costs of more conventional novel treatments. Nevertheless, specialty drugs can offer good value for various complex and burdensome diseases.” l

Wealth Management

Disability Insurance: Deciphering the COLA Rider

By Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF

I

f you are unable to work due to a sickness or injury, disability insurance can help you meet your expenses and maintain your standard of living. One of the options available when purchasing an individual disability insurance policy is the cost of living adjustment (COLA) rider.

What Is the COLA Rider?

The COLA rider is designed to help your disability insurance benefit keep pace with inflation. These riders generally adjust your policy’s monthly benefit on an annual basis, based on a fixed percentage or tied to the consumer price index after you have been disabled for 12 months.

These adjustments apply to total and residual disabilities and can be based on a simple or compound basis. Although expensive, this rider can provide significant increases to your monthly benefit if you are disabled early in your career.

Is the COLA Rider Worth Purchasing?

My general rule is that the younger you are and the fewer assets you have accumulated, the more impor­ tant the COLA rider is and the more it should be part of your policy. However, if you are not opting for the maximum amount of coverage that you qualify for based upon your earned income, you should consider removing the COLA rider and using the dollars you would have allocated to the COLA rider to purchase a larger monthly benefit. Remember, the COLA rider will not increase your monthly benefit until you have been disabled for 12 months. Therefore, if you are not disabled for a long-term period, and have been paying premiums for a COLA rider,

you may not realize much of an economic benefit from the rider.

(assuming a total disability began on the effective date of the policy and continued until the age of 65 years) would be $5.70 million. If you purchased a policy with a $13,000 monthly benefit and no COLA rider, the maximum potential benefit for the same disability would be $4.64 million.

Ideally, should you decide to purchase the COLA rider, I would suggest one that is compounded, and the higher the maximum is the better, taking overall policy premiums into consideration. While the example above utilized the sample company’s 3% compound COLA rider, a similar analysis can easily be done for most insurance companies.

Do the Math Assume that you are a 35-year-old male hematologist–oncologist in New York earning $290,000 per year. You were planning to purchase $10,000 per month of individual coverage from an established insurance company (you qualified for $13,000 per month, but wanted to reduce your premium outlay), payable after 90 days of disability to age 65 years with an enhanced residual disability rider and a 3% compound COLA rider. The monthly premium would be $267, including a 10% association discount. If you removed the COLA rider, the monthly premium would be reduced to $203; this is a savings of $64, or approximately 24% of the cost of the policy.

If you took that premium savings, how much additional monthly benefit would that allow you to purchase?

A policy for $13,000 per month, payable after 90 days to age 65 years would have a monthly premium of $262, including a 10% association discount. This is almost identical to the premium for the $10,000 monthly benefit with the COLA rider included.

In this scenario, does it make sense to forgo the COLA rider?

What is the break-even period? That is easy to calculate. If you took $10,000 monthly and invested it at a 3% compound rate of return, in 10 years (1 year of disability plus 9 years of investing at 3%), the $10,000 would grow to $13,048.

By the same token, if you purchased a policy with a $10,000 monthly benefit and a 3% compound COLA rider, the maximum potential benefit for total disability

March 2015

Summary The COLA rider is designed to help your disability insurance benefits keep pace with inflation. Generally, the younger you are and the fewer assets you have accumulated, the more important the COLA rider is and the more it should be part of your policy. However, if you are not opting for the maximum amount of coverage that you qualify for based upon your earned income, you should consider removing the COLA rider and using the dollars you would have allocated to the COLA rider to purchase a larger monthly benefit. l 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 at 800-481-6447 or by e-mail to Lkeller@physicianfinancialservices.com.

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Clinical Trial Tracker

Trials Under Way for Patients with Brain Cancer

T

he following clinical trials are currently recruiting patients with brain cancer for inclusion in several investigations.

Each trial description includes the NLM Identifier to use as a reference with ClinicalTrials.gov.

1

Perifosine and Temsirolimus for Recurrent/Progressive Malignant Gliomas This phase 2, parallel-group, open-­ label study will assess the effective­­ ness of temsirolimus and perifosine combination therapy in treating recurrent or progressive brain tumors.

Patients aged ≥18 years who have received previous radiotherapy and tem­ ozolomide for the treatment of malignant glioma and who have (1) a Karnofsky performance score of ≥70, (2) a life expectancy >8 weeks, (3) normal organ and marrow function, and (4) adequate renal and liver function may enroll if other criteria are met. Patients are randomized to receive cytoreductive surgery or no procedure. After antiemetic prophylaxis, both groups will receive perifosine according to protocol.

Primary outcome measures include radiographic response and 6-month, progression-free survival.

The secondary outcome measure is median overall survival, measured from the time the study drug is first administered for up to 48 months or until the patient dies. This study is expected to enroll 17 patients in New York City. For more information, contact Andrew B. Lassman, MD, at 212-342-0571 or ABL7@ cumc.columbia.edu. The NLM Identifier is NCT02238496.

2

Valproic Acid, Radiation, and Bevacizumab in Children This phase 2, single-group, open-­ label trial examines whether the combination of valproic acid and

30

I

bevacizumab with surgery and radiation will reduce brain tumors more effectively and improve the possibility of cure. Patients 3 to 21 years of age with high-grade gliomas who have not received previous chemotherapy, radiation, biologic therapy, or bone marrow transplants, and who have a Karnofsky or Lansky performance score of ≥50 within 2 weeks of study enrollment may participate if other criteria are met.

Patients will be encouraged to have the maximal surgical resection that can be performed safely before entering into the study. All patients will receive valproic acid in a dose-escalation sequence and bevacizumab intravenously every 2 weeks during the maintenance phase, for a maximum of 24 months. Radiation therapy will start within 30 days of the patient’s definitive surgical procedure. Primary outcome measures are event-free survival and valproic acid toxicity, assessed over a time frame of 24 months. This study is expected to enroll 56 patients in Oklahoma City, OK, and at various sites throughout Texas. For more information, contact Jack Su, MD, at 832-822-4306 or jmsu@txch.org, or Susan Blaney, MD, at 832-822-4586 or smblaney@txch.org. The NLM Identifier is NCT00879437.

3

Palbociclib Isethionate for Treatment of Younger Patients The goal of this phase 1, open-label study is to characterize the side effects and best dose of palbociclib isethionate in treating younger patients with recurrent, progressive, or refractory brain tumors.

Patients aged 4 to 21 years who received their last dose of myelosuppressive anticancer chemotherapy ≥3 weeks, nitrosourea ≥6 weeks, or biologic agent ≥7 days before enrolling in the trial are eligible to participate if other criteria are met. All pa-

Oncology Practice Management

I March 2015

tients will receive the study drug daily on days 1 to 21. This treatment repeats every 28 days for 26 courses in the absence of disease progression or unacceptable toxicity.

Primary outcomes are the maximum tolerated dose of palbociclib isethionate and the incidence of adverse events, both assessed for a time frame of 4 weeks to 1 month. Secondary outcome measures are objective responses (ie, partial and complete response), and individual and population pharmacokinetic parameters. This study is expected to enroll 40 patients in several locations throughout the United States. For more information, contact Wint M. Swe, MBA, MBBS, at wint.swe@ stjude.org. The NLM Identifier is NCT02255461.

4

Postapproval Study of NovoTTF-100A The purpose of this phase 4, nonrandomized, parallel-assignment study is to confirm that the efficacy of the NovoTTF-100A System in patients with recurrent glioblastoma multiforme is comparable to that of basic standard-of-care (BSC) chemotherapy. Patients aged ≥22 years with a Karnofsky performance score of ≥70, a histologic diagnosis of glioblastoma multiforme, and who have received maximal, safe, surgical resection; radiation therapy; and concomitant and maintenance temozolomide may enroll if other criteria are met. Patients will receive either BSC or NovoTTF-100A monotherapy.

The primary outcome is the overall survival, measured 5 years from initiation of accrual. Secondary outcome measures include the change in neurocognitive function from baseline, genetic profiling of tumors and correlation with response to treatment, and the adverse event profile. This study is expected to en-

Clinical Trial Tracker

roll 486 patients at sites throughout the United States. For more information, contact Ghazala Kabani at patientinfo@novocure.com. The NLM Identifier is NCT01756729.

5

Photodynamic Therapy for Brain Tumors This phase 1, open-label study evaluates the maximum tolerated dose and preliminary effectiveness trends of photodynamic therapy (PDT) in children. Patients aged 6 months to 18 years with relapsed or refractory brain tumors and potentially resectable disease, and whose disease does not have a known curative therapy or therapy proven to prolong survival with an acceptable quality of life may enroll if other criteria are met. All patients will receive intravenous Photofrin in a dose-escalation manner approximately 24 hours before tumor resection surgery and PDT. The primary outcome measure is the maximum tolerated dose of Photofrin in pediatric patients. Dose-limiting toxicities observed can include neurotoxicity, photosensitivity, ocular sensitivity, and any other toxicity ≥grade 4 within the same period.

The secondary outcome measure is brain tumor response occurring within 3 years of receiving PDT. This trial is expected to enroll 24 patients in Wauwatosa, WI. For more information, contact Michael E. Kelly, MD, PhD, at 414-266-6471 or mekelly@mcw.edu. The NLM Identifier is NCT01682746.

6

Genetically Modified Neural Stem Cells, Flucytosine, and Leucovorin The objective of this phase 1, open-label study is to determine the side effects and best dose of genetically modified neural stem cells (NSCs) and flucytosine in combination with leucovorin. Patients aged ≥18 years with recurrent, high-grade gliomas may enroll if other criteria are met.

All patients will receive NSCs intracranially on days 1 and 15. Flucytosine is given orally on days 4 to 10 and 18 to 24. Patients may be given leucovorin orally, depending on when they enter the study.

Primary outcome measures include the maximum tolerated dose and incidence of dose-limiting toxicities, the incidence of all adverse events and toxicities, and clinically significant allergic reactions to NSCs. Secondary outcome measures include T-cell responses, antibodies against NSCs, and pharmacokinetic parameters. This trial is expected to enroll 24 patients in Duarte, CA. For more information, contact Alexandra Ching, NP, at 626-471-9393 or neurosurgery@coh.org. The NLM Identifier is NCT02015819.

comes are progression-free survival, number of pseudoprogression cases, and the pharmacokinetic parameters of veliparib. This study is expected to enroll 66 patients at multiple locations throughout the United States.

For more information, contact Patricia A. Baxter at 832-824-4681 or pabaxter@txch.org. The NLM Identifier is NCT01514201.

8

Selumetinib in Young Patients with Recurrent or Refractory Low-Grade Glioma This phase 1/2, single-group, open-label trial evaluates the side effects and best dose of selumetinib and its efficacy in the treatment of recurrent or refractory low-grade glioma. Patients aged 3 to 21 years who have not received myelosuppressive anticancer chemotherapy for ≤3 weeks or a nitrosourea for ≤6 weeks before study registration may enroll if other criteria are met. All patients will receive selumetinib orally twice daily on days 1 to 28. Courses repeat every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

Primary outcome measures are the maximum tolerated dose and recommended phase 2 dose of selumetinib (as determined by dose-limiting toxicities), the stratum-specific objective response rate sustained for 8 weeks, objective response, and disease stabilization rates. Secondary outcome measures include plasma drug concentrations and pharmacokinetic parameters, stratum-specific progression-free survival (PFS) distribution, the presence or absence of BRAF V600E mutations or BRAF KIAA1549 fusion, and PFS in patients with recurrent disease. This trial is expected to enroll 135 patients in locations throughout the United States. For more information, contact Jason R. Fangusaro at 312-227-4846 or jfangusaro@lurie childrens.org. The NLM Identifier is NCT01089101.

7

Veliparib, Radiation Therapy, and Temozolomide for Younger Patients This phase 1/2 trial studies the side effects and best dose of veliparib in younger patients when given with radiation therapy and temozolomide. Patients aged ≤21 years who have newly diagnosed diffuse intrinsic pontine gliomas, have a Karnofsky or Lansky performance score of ≥50 (for patients >16 years of age or ≤16 years of age, respectively), and are treatment-naïve except for surgery and/or steroids may enroll if other criteria are met. All patients will receive a dose escalation of veliparib orally 5 days a week for 6 to 7 weeks. During maintenance therapy, all patients will receive veliparib and temozolomide on days 1 to 5. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Primary outcome measures are the maximum tolerated dose of veliparib, the feasibility of intrapatient dose escalation of temozolomide during maintenance therapy with veliparib, and overall survival. Secondary out-

March 2015

Continued on page 43

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Drug Update

Cyramza (Ramucirumab) Approved for the Treatment of Advanced Gastric Cancer and Metastatic Non–Small-Cell Lung Cancer

By Loretta Fala, Medical Writer

G

astric cancer and lung cancer impose a substantial burden on patients. In light of the high mortality rate and quality-of-life issues associated with these 2 types of cancer, there is a marked need for additional therapeutic options to improve outcomes for patients with gastric or lung cancer.

Gastric Cancer The prevalence of gastric cancer has been on the decline in the United States in the past 80 years.1 Gastric cancer is most common in older people aged >65 years, affecting 6 in 10 people in this age-group. It is estimated that 24,590 new cases of gastric cancer will be diagnosed in the United States in 2015.1 The gastroesophageal junction (GEJ) is the area just beneath the diaphragm, where the esophagus joins the stomach. GEJ adenocarcinoma (or stomach cancer) is a cancer that affects this region of the gastric tract.2 As with other types of cancer, early detection and advances in treatment have improved the outlook for patients with gastric cancer.

However, most gastric cancers are diagnosed at advanced stages rather than at early stages, resulting in a low survival rate.3 Overall, the 5-year relative survival rate of all patients with gastric cancer in the United States is approximately 29%.3 The total US expenditures for stomach cancer were estimated to be $1.8 billion in 2010.4 Copyright © 2015 American Health & Drug Benefits. Used with permission. All rights reserved.

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Lung Cancer Lung cancer is the second most common cancer in men and in women in the United States, with an estimated 221,200 new cases projected for 2015.5 Non–small-cell lung cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer.6 Overall, lung cancer claims more lives than any other type of cancer—more than that of colon, breast, and prostate cancers combined—accounting for approximately 27% of all cancer deaths in the United States.5 Although the 5-year survival rate for localized lung cancer is 54%, only 15% of lung cancers are diagnosed at this stage.7 For all lung cancer cases diagnosed between 2003 and 2009, the 1-year relative survival rate was 43%, and the 5-year relative survival rate was 17%.7 Lung cancer is the third costliest cancer in the United States, after breast cancer and colo­ rectal cancer, with a total estimated annual cost of $10.3 billion.8 The Vascular Endothelial Growth Factor Pathway Angiogenesis, the formation of new capillaries and blood vessels, is a process involved in tumor growth.9 Vascular endothelial growth factor (VEGF) is a primary mediator of angiogenesis in normal physiology and in certain diseases.9 VEGF and VEGF receptor-2–mediated signaling and angiogenesis may play a key role in the pathogenesis of gastric cancer and lung cancer.10-12 The blockade of VEGF receptor-2 signaling inhibits angiogenesis (ie, blood supply) to tumors.12 A number of small molecule inhibitors and anti-

Oncology Practice Management

I March 2015

body-based agents that target the VEGF pathway have been studied across various cancer types.9 In clinical studies, targeting the VEGF receptor-2 pathway has shown promise as a second-line treatment for patients with gastric or lung cancer.10-12

Ramucirumab Receives Several FDA Approvals in 2014 A New Option for Advanced Stomach Cancer

On April 21, 2014, ramucirumab (Cyramza; Eli Lilly), a human VEGF receptor-2 antagonist, was approved by the US Food and Drug Administration (FDA) as a single agent for the treatment of patients with advanced stomach cancer or GEJ adenocarcinoma that has progressed with or after fluoropyrimidine- or platinum-containing chemotherapy.13 Ramucirumab is a recombinant human immunoglobulin G1 monoclonal antibody, also referred to as an angiogenesis inhibitor (ie, blocking the blood supply to tumors).13 The FDA granted ramucirumab a priority review based on its potential to provide a significant improvement in safety or effectiveness in the treatment of advanced gastric cancer or GEJ adenocarcinoma. The FDA also designated ramucirumab as an orphan drug because it is approved for a rare disease.13 According to Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, “Although the rates of stomach cancer in the United States have decreased over the past 40 years, patients require new treatment options, particularly when

Drug Update

they no longer respond to other therapies. Cyramza is a new treatment option that has demonstrated an ability to extend patients’ lives and slow tumor growth.”13 Expanded Indication

On November 5, 2014, the FDA expanded the initial indication of ramucirumab to be used alone or with paclitaxel for the treatment of patients with advanced stomach cancer that has progressed with or after previous fluoropyrimidine- or platinum-containing chemotherapy.14

A New Option for Non–SmallCell Lung Cancer

On December 12, 2014, the FDA approved ramucirumab to be used in combination with docetaxel for the treatment of patients with metastatic NSCLC that has progressed with or after platinum-based chemotherapy.15 In patients with lung cancer and the EGFR or ALK genetic mutations, ramucirumab should only be used after their disease has progressed while using FDA-approved therapies for these mutations.16 Dr Pazdur commented, “Today’s approval is the third indication that Cyramza has received in 2014.”15 He further stated, “The commitment to study Cyramza in a variety of malignancies provides important treatment options to patients.”15

Mechanism of Action Ramucirumab is a VEGF receptor-2 antagonist that specifically binds VEGF receptor-2 and blocks the binding of VEGF receptor ligands, VEGF-A, VEGF-C, and VEGF-D. As a result, ramucirumab inhibits ligand-stimulated activation of VEGF receptor-2, thereby inhibiting ligand-induced proliferation and migration of human endothelial cells.16 Dosing and Administration Ramucirumab is administered as

Table 1 The REGARD Trial: Ramucirumab versus Placebo in Gastric Cancer Ramucirumab + best supportive therapy (N = 238)

Efficacy measure

Placebo + best supportive therapy (N = 117)

Overall survival Deaths, N (%) Median, mo Hazard ratio

179 (75)

99 (85)

5.2 (95% CI, 4.4-5.7)

3.8 (95% CI, 2.8-4.7)

0.78 (95% CI, 0.60-0.998)

Stratified log-rank P value

.047

Progression-free survival Events, N (%) Median, mo Hazard ratio

199 (84)

108 (92)

2.1 (95% CI, 1.5-2.7)

1.3 (95% CI, 1.3-1.4)

0.48 (95% CI, 0.38-0.62)

Stratified log-rank P value

<.001

CI indicates confidence interval.

Source: Cyramza (ramucirumab) injection prescribing information; December 2014.

an intravenous (IV) infusion only. It should not be administered as an IV push or bolus.16 For patients with advanced gastric cancer, the recommended dose of ramucirumab, either as a single agent or in combination with weekly pac­ litaxel, is 8 mg/kg every 2 weeks.16 For patients with metastatic NSCLC, the recommended dose of ramucirumab is 10 mg/kg, administered intravenously on day 1 of a 21-day cycle, before the infusion of docetaxel.16 Ramucirumab is available as an injection in single-dose vials in a 100-mg/10-mL (10 mg per mL) solution and in a 500-mg/50-mL (10 mg per mL) solution.16

cinoma.10,16 The patients (median age, 60 years) received either an IV infusion of ramucirumab 8 mg/kg or placebo every 2 weeks. The primary efficacy end point was overall survival (OS), and the supportive outcome measure was progression-free survival (PFS).10,16 The efficacy results from the REGARD trial are shown in Table 1.

Patients randomized to receive ramucirumab had significant improvements in OS and PFS compared with patients randomized to placebo.10,16 The median OS was 5.2 months in the ramucirumab group compared with 3.8 months in the placebo group.10,16 Moreover, treatment with ramucirumab was associated with a 52% reduction in the risk for disease progression or death from any cause compared with placebo.10 According to the REGARD study investigators, ramucirumab is the first biologic agent given as a monotherapy to demonstrate survival benefits in patients with advanced gastric cancer or GEJ adenocarcinoma that had progressed after first-line chemotherapy.10 The investigators stated that these findings reinforce the importance of targeting the VEGF recep-

Clinical Studies

The REGARD Trial: Gastric Cancer

The REGARD trial was a multinational, randomized, double-blind study that evaluated the efficacy of ramucirumab plus best supportive care compared with placebo plus best supportive care and randomized (in a 2:1 ratio) 355 patients with locally advanced or metastatic gastric cancer, including GEJ adenocar-

Continued on page 40

March 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

We’ve Got You Covered Helping Your Patients Financial assistance is available for patients.* Private Insurance $5000/month copay assistance, up to $12,000/year

Medicare/Medicaid Referrals to Independent Copay Foundations†

Uninsured or Underinsured Free XTANDI® (enzalutamide) capsules

New Patients Awaiting Coverage Decision Free XTANDI through XTANDI Quick Start+™ Program

*Subject to eligibility. Void where prohibited by law. Restrictions may apply. † XTANDI Support SolutionsSM has no control over the decisions made by and does not guarantee support by these independent copay foundations.

To learn more about XTANDI Support Solutions or enroll your patients today:

1-855-8XTANDI (855-898-2634) 8 AM – 8 PM ET

(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,

XTANDISupportSolutions.com

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

0.3

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

Drug Update

Cyramza (Ramucirumab) Approved... Continued from page 35 tor-2 pathway when treating patients with advanced gastric cancer.10 The RAINBOW Trial: Gastric Cancer

The RAINBOW trial, a multinational, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel, included 665 patients (randomized in a 1:1 ratio) with locally advanced or metastatic gastric cancer (including GEJ adenocarcinoma) who received platinum-containing and fluoropyrimidine-containing chemotherapy.11,16 The patients (median age, 61 years) were randomized to receive either ramucirumab 8 mg/kg or placebo as an IV infusion on days 1, 8, and 15 of each 28-day cycle. The primary efficacy outcome measure was OS, and the supportive outcome measures were PFS and objective response rate.11,16 As shown in Table 2, treatment with ramucirumab plus paclitaxel

showed a significantly longer OS compared with placebo plus paclitaxel (9.6 months vs 7.4 months, respectively).11,16 Moreover, ramucir­ umab plus paclitaxel demonstrated significant improvements in PFS and objective response rate compared with placebo plus paclitaxel.11,16 The RAINBOW study’s investigators suggested that ramucirumab plus paclitaxel could be considered a standard second-line treatment option for patients with advanced gastric cancer.11 The REVEL Trial: Non–Small-Cell Lung Cancer

The REVEL trial was a multinational, randomized, double-blind study in patients with NSCLC that had progressed while receiving or after receiving 1 platinum-based therapy regimen for locally advanced or metastatic NSCLC.12,16 Patients (median age, 62 years) received ei-

Table 2 T he RAINBOW Trial: Ramucirumab plus Paclitaxel versus Placebo plus Paclitaxel in Gastric Cancer Efficacy measure

Ramucirumab + paclitaxel (N = 330)

Placebo + paclitaxel (N = 335)

Overall survival Deaths, N (%) Median, mo

256 (78)

260 (78)

9.6 (95% CI, 8.5-10.8)

7.4 (95% CI, 6.3-8.4)

Hazard ratio

0.81 (95% CI, 0.68-0.96)

Stratified log-rank P value

.017

Progression-free survival Events, N (%) Median, mo

279 (85)

296 (88)

4.4 (95% CI, 4.2-5.3)

2.9 (95% CI, 2.8-3.0)

Hazard ratio

0.64 (95% CI, 0.54-0.75)

Stratified log-rank P value

<.001

Objective response rate (complete response plus partial response) Rate, %

28 (95% CI, 23-33)

Stratified CMH P value

16 (95% CI, 13-20) <.001

CI indicates confidence interval; CMH, Cochran-Mantel-Haenszel.

Source: Cyramza (ramucirumab) injection prescribing information; December 2014.

ther ramucirumab 10 mg/m2 intravenously plus docetaxel 75 mg/m2 intravenously every 21 days or placebo plus docetaxel 75 mg/m2 intravenously every 21 days. The primary end point was OS, and the supportive outcome measures were PFS and objective response rate.12,16 Efficacy results from the REVEL trial are shown in Table 3. Patients in the ramucirumab plus docetaxel group had statistically significant improvements in OS and PFS compared with patients in the placebo plus docetaxel group. Moreover, the objective response rate (complete response or partial response) for patients receiving ramucirumab plus docetaxel was 23% (95% confidence interval, 20-26) compared with 14% (95% confidence interval, 11-17) for patients receiving placebo plus docetaxel (P <.001).16

Safety and Adverse Events The most common adverse reactions observed in patients treated with single-agent ramucirumab at a rate of ≥10% and ≥2% higher than placebo were hypertension (16%) and diarrhea (14%).16 In patients treated with ramuciru­ mab plus paclitaxel, the most common adverse reactions observed at a rate of ≥30% and ≥2% higher than placebo plus paclitaxel were fatigue/ asthenia (57%), neutropenia (54%), diarrhea (32%), and epistaxis (31%).16 In patients receiving ramuciru­ mab plus docetaxel, the most common adverse reactions observed at a rate of ≥30% and ≥2% higher than placebo plus docetaxel were neutropenia (55%), fatigue/asthenia (55%), and stomatitis/mucosal inflammation (37%).16 There are no contraindications associated with ramucirumab.16 Drug Interactions No pharmacokinetic interactions Continued on page 42

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Oncology Practice Management

I March 2015

Promote the value of oncology navigation to your organization and bottom line

Network with your oncology navigation team at the

AONN+ West Coast Regional Meeting May 18 – 20, 2015 in Seattle, Washington

“

Financial Navigators a new buzz word is circling cancer centers right now. Navigators and patient advocates need to make sure that there is a clear understanding on the part of the patient what the cost of care means for them. Start talking with your oncology navigation team and see what the plans are for obtaining cost information for patients going forward, and get to know the financial navigator who will be involved in your clinic by attending the AONN+ West Coast Regional Meeting.”

Lillie Shockney, RN, BS, MAS, CBPN-IC, Program Director, Academy of Oncology Nurse & Patient Navigators (AONN+)

TUESDAY | MAY 19, 2015 10:45 AM - 11:45 AM

Special Session in Partnership with the Association for Oncology Practice Management

Value-Based Strategies for Navigation

with:

LINDA BOSSERMAN, MD, FACP Assistant Clinical Professor Community Medical Oncologist Breast Cancer and Oncology Medical Home Specialist City of Hope Medical Group

Meeting Topics Include:

Who Should Attend:

Best practices in navigation

Continuing education units

Oncology nurse navigators

Oncology social workers

Nuances in providing valuebased care in oncology

Psychosocial care for cancer patients

Practice managers

Administrators

Impact of prehabilitation and rehabilitation

Commission on Cancer case studies

Financial Counselors

Case managers

Survivorship

Networking opportunities

Patient or non-clinically licensed navigators

Oncology nurses and nurse practitioners

Visit AonnOnline.org to find out more and register today!

NON-MEMBERS EARLY BIRD REGISTRATION (ends 1/31/15) $135 Clinically Licensed | $110 Non-Clinically Licensed MEMBERS (ends 5/18/15) $115 Clinically Licensed | $100 Non-Clinically Licensed

Drug Update

Cyramza (Ramucirumab) Approved... Continued from page 40 Table 3 T he REVEL Trial: Ramucirumab plus Docetaxel versus Placebo plus Docetaxel in Non–Small-Cell Lung Cancer Efficacy measure

Ramucirumab + docetaxel (N = 628)

Placebo + docetaxel (N = 625)

Overall survival Deaths, N (%) Median, mo

428 (68)

456 (73)

10.5 (95% CI, 9.5-11.2)

9.1 (95% CI, 8.4-10.0)

Hazard ratio

0.86 (95% CI, 0.75-0.98)

Stratified log-rank P value

.024

Progression-free survival Events, N (%) Median, mo

558 (89)

583 (93)

4.5 (95% CI, 4.2-5.4)

3.0 (95% CI, 2.8-3.9)

Hazard ratio

0.76 (95% CI, 0.68-0.86)

Stratified log-rank P value

<.001

CI indicates confidence interval.

Source: Cyramza (ramucirumab) injection prescribing information; December 2014.

were observed between ramucirumab and paclitaxel or between ramucir­ umab and docetaxel.16

Warnings and Precautions Boxed warning. Ramucirumab was approved with a boxed warning about the increased risk for hemorrhage, including severe and sometimes fatal hemorrhagic events. Ramucirumab should be discontinued in patients who have severe bleeding.16 Arterial thromboembolic events.

Serious, sometimes fatal, arterial thromboembolic events occurred in clinical trials. Ramucirumab should be permanently discontinued in patients who experience a severe arterial thromboembolic event.16 Hypertension. An increased incidence of severe hypertension occurred in patients receiving ramucirumab as a single agent and in patients receiving ramucirumab combined with paclitaxel and combined with docetaxel. Hypertension should be controlled before initiating treatment with ramucirumab.

42

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Blood pressure should be monitored every 2 weeks or more frequently as indicated during treatment.16 Infusion-related reactions. Patients should be monitored for the signs and symptoms of infusion-related reactions during the infusion of ramucirumab.16 Gastrointestinal perforation. As an antiangiogenic therapy, ramucirumab can increase the risk for gastrointestinal perforation, which can be fatal. Ramucirumab should be permanently discontinued in patients with a gastrointestinal perforation.16 Impaired wound healing. Ramucirumab has not been studied in patients with serious or nonhealing wounds. As an antiangiogenic therapy, ramucirumab has the potential to adversely affect wound healing. Ramucirumab should be withheld before surgery and resumed after surgery based on adequate wound healing. If wound-healing complications develop during treatment, ramucirumab should be discontinued until the wound is fully healed.16

Oncology Practice Management

I March 2015

Clinical deterioration of cirrhosis. New-onset or worsening encephalopathy, ascites, or hepatorenal syndrome can occur in patients with Child-Pugh class B or C cirrhosis.

Ramucirumab should be only used in patients with Child-Pugh class B or C cirrhosis if the potential benefits of treatment are judged to outweigh the risks of clinical deterioration.16 Reversible posterior leukoencephalopathy syndrome. This syndrome has been reported in clinical studies with ramucirumab. If the diagnosis of reversible leukoencephalopathy is confirmed with magnetic resonance imaging, ramucirumab should be discontinued.16

Use in Specific Populations Pregnancy. Based on its mechanism of action, ramucirumab may cause fetal harm. If ramucirumab is used during pregnancy, or if the patient becomes pregnant while taking the drug, assess the potential hazard to the fetus.16 Nursing mothers. It is not known whether ramucirumab is excreted in human milk. Whether the patient should discontinue nursing or discontinue the drug is dependent on the importance of the drug to the mother.16 Pediatric use. The safety and effectiveness of ramucirumab in pediatric patients have not been established.16 Geriatric use. Among patients receiving ramucirumab in the 2 gastric cancer clinical trials, no overall differences in safety or efficacy were observed between patients aged ≥65 years and younger patients.16 Renal impairment. No dose adjustment is recommended for patients with renal impairment.16 Hepatic impairment. No dose adjustment is recommended for patients with mild hepatic impairment.16 Reproductive potential. Ramucir­ umab may impair fertility. Females of reproductive potential should be ad-

Drug Update

vised to avoid getting pregnant while receiving ramucirumab and for at least 3 months after the last dose.16

Conclusion In 2014, ramucirumab received FDA approval for 3 indications—as a single agent or in combination with paclitaxel for advanced gastric cancer, and in combination with docetaxel for metastatic NSCLC. These FDA approvals mark the availability of an additional second-line treatment option for 2 types of advanced cancer.

In patients with advanced stomach cancer or GEJ adenocarcinoma, ramucirumab as a single agent and in combination with paclitaxel demonstrated significant improvements in OS and PFS compared with placebo, and compared with placebo in combination with paclitaxel, based on findings from the REGARD and the RAINBOW clinical trials.

In patients with metastatic NSCLC, ramucirumab plus docetaxel

showed significant improvements in OS and PFS compared with placebo plus docetaxel, as was demonstrated in the REVEL study. l

February 9, 2015.

9. Sullivan LA, Brekken RA. The VEGF family in cancer and antibody-based strategies for their inhibition.

MAbs. 2010;2:165-175.

10. Fuchs CS, Tomasek J, Yong CJ, et al; for the REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31-39.

11. Wilke H, Muro K, Van Cutsem E, et al; for the RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224-1235.

12. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384:665-673.

13. US Food and Drug Administration. FDA approves Cyramza for stomach cancer. Press release. April 21, 2014. www.fda.gov/NewsEvents/Newsroom/PressAnnounce ments/ucm394107.htm. Accessed February 9, 2015.

14. Eli Lilly and Company. Lilly’s Cyramza (ramucir­ umab) in combination with paclitaxel granted FDA approval for advanced gastric cancer after prior chemotherapy. Press release. November 5, 2014. https://investor. lilly.com/releasedetail.cfm?releaseid=880745. Accessed February 6, 2015.

15. US Food and Drug Administration. FDA expands approved use of Cyramza to treat aggressive non-small cell lung cancer. Press release. December 12, 2014. www.fda.gov/NewsEvents/Newsroom/PressAnnounce ments/ucm426720.htm. Accessed February 9, 2015.

16. Cyramza (ramucirumab) injection [prescribing information]. Indianapolis, IN: Eli Lilly and Company; December 2014.

References

1. American Cancer Society. What are the key statistics about stomach cancer? Revised January 9, 2015. www. cancer.org/cancer/stomachcancer/detailedguide/stomachcancer-key-statistics. Accessed February 9, 2015.

2. American Cancer Society. What is stomach cancer? Revised January 9, 2015. www.cancer.org/cancer/ stomachcancer/detailedguide/stomach-cancer-what-isstomach-cancer. Accessed February 9, 2015.

3. American Cancer Society. Survival rates for stomach cancer, by stage. Revised January 9, 2015. www.cancer. org/cancer/stomachcancer/detailedguide/stomachcancer-survival-rates. Accessed February 8, 2015.

4. National Cancer Institute. Costs of cancer care. In: Cancer Trends Progress Report—2011/2012 Update.

August 2012. http://progressreport.cancer.gov/doc_ detail.-asp?pid=1&did=2007&chid=75&coid=726.

Accessed February 9, 2015.

5. American Cancer Society. What are the key statistics about lung cancer? Revised January 20, 2015. www. cancer.org/cancer/lungcancer-non-smallcell/detailed guide/non-small-cell-lung-cancer-key-statistics. Accessed February 9, 2015.

6. American Cancer Society. Non-small cell lung cancer. www.cancer.org/cancer/lungcancer-non-smallcell/.

Accessed February 10, 2015.

7. American Cancer Society. Cancer facts & figures 2014.

2014. www.cancer.org/acs/groups/content/@research/ documents/webcontent/acspc-042151.pdf. Accessed February 10, 2015.

8. Hardison BL. The financial burden of cancer. NCI Benchmarks. April 23, 2010. http://benchmarks.cancer. gov/2010/04/the-financial-burden-of-cancer/. Accessed

Trials Under Way... Continued from page 31

9

Phase 1 Study of a Dendritic Cell Vaccine This phase 1, parallel-assignment study tests the safety and effectiveness of a dendritic cell vaccine in patients with newly diagnosed or recurrent glioblastoma. Patients aged ≥18 years who have had a complete resection of their tumor and have a Karnofsky performance score of ≥70 may enroll if other criteria are met. Patients are randomized to receive the dendritic cell vaccination and either standard temozolomide chemotherapy and involved field radiation therapy, or, for patients who were previously treated with bevacizumab, an optional retreatment with this drug.

Primary outcome measures assess safety and tolerability, the number of

of bevacizumab and carboplatin can help control recurrent ependymoma.

Patients aged ≥18 years with adequate bone marrow, liver, and renal function, and a Karnofsky performance score of ≥60 may enroll if other criteria are met. All patients will receive bevacizumab 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle. Carboplatin will be given intravenously on day 1 of each 28-day cycle. Primary outcome measures are the number of patients with progression-free survival at 1 year posttreatment. This study is expected to enroll 46 patients in Boston, New York City, and Houston, TX. For more information, contact Mark R. Gilbert, MD, BS, at 713792-2883. The NLM Identifier is NCT01295944. l

serious adverse events, and treatment-related toxicities over the course of 1 year. Secondary outcome measures evaluate overall and progression-free survival, health-related quality-of-life parameters, the overall response rate, immune response, and tumor stem-cell antigen expression, all over the course of 2 years. This trial is expected to enroll 40 patients in Los Angeles. For more information, contact Cherry Sanchez, RN, at 310-423-6839 or cherry.sanchez@ cshs.org. The NLM Identifier is NCT02010606.

10

Carboplatin and Bevacizumab The objective of this phase 2, single-group, open-label trial is to determine whether the combination

March 2015

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www.OncPracticeManagement.com

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MAY 18 – 20, 2015 • MOTIF SEATTLE HOTEL • SEATTLE, WASHINGTON The Academy of Oncology Nurse & Patient Navigators (AONN+) 2015 West Coast Regional Meeting offers navigation professionals access to a host of educational sessions, networking opportunities and poster presentations.

Conference Chair and AONN+ Program Director

EDUCATIONAL OBJECTIVES After completing this activity, the participant should be able to:

Lillie Shockney, RN, BS, MAS University Distinguished Service Associate Professor of Breast Cancer Administrative Director, The Johns Hopkins Breast Center Director, Cancer Survivorship Programs at the Sidney Kimmel Cancer Center at Johns Hopkins Associate Professor, JHU School of Medicine Departments of Surgery, Oncology & Gynecology and Obstetrics Associate Professor, JHU School of Nursing, Baltimore, Maryland

Conquer RY 201 5 • VOL . 1 • NO . 1 URAL

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CONQUER™ magazine, featuring articles written by and for patients with cancer, survivors, nurse navigators and other oncology team members.

IGHTS

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Assess strategies for navigating diverse patient populations by cancer type and environmental factors in this specific region Define methods for providing patient support and guidance in the age of personalized cancer care Evaluate best practices regarding survivorship and psychosocial care in this specific region Provide appropriate care and counsel for patients and their families Want to know more? Additional information about educational objectives and continuing education can be found at: AonnOnline.org/Regionals/West-Coast.

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EBRUA

Discuss regional issues regarding the evolution of the role of navigation in healthcare

WHO SHOULD ATTEND: Oncology nurse navigators

Oncology social workers

Practice managers

Administrators

Financial counselors

Case managers

Patient or non-clinically licensed navigators

Oncology nurses and nurse practitioners

2:57 PM

WCRM_AgendaAsize031715

THANK YOU TO OUR SPONSORS Corporate Platinum Sponsors

Oncology

Corporate Gold Sponsors

Cornerstone Sponsor

AGENDA* Monday May 18th 6:30 - 8 PM

Dinner and Multiple Myeloma Presentation (non–CE-certified activity)

Tuesday May 19th

Wednesday May 20th

AM Sessions

AM Sessions

6:45 - 8 8:15 - 8:30

(non–CE-certified activities)

Breakfast N.E.X.T. Session

9:30 - 10:30

8:15 - 8:30

8:30 - 9:30

General Session 2: Complete Care – The New Trend in Doctor Visits

Genetic Counselor and the Managing Director of the Breast Cancer

Development, Southern California Permanente Medical Group

Survivorship Center, University of Kansas Cancer Center

Kristen Andrews | Proactive Care Group Lead, Southern California

10:45 - 11:45

9:30 - 10:30

General Session 3: Value-Based Strategies for Navigation

Program, University of Colorado Health-North Kathleen Michie, PT, MT, CLT | Oncology Services Program Manager,

Community Medical Oncologist, Breast Cancer and Oncology

Oncology Rehabilitation and Integrative Therapies

Medical Home Specialist, City of Hope Medical Group

PM Sessions 1:15 - 2

2 - 2:45

Lunch N.E.X.T. Session - sponsored by Takeda Oncology

General Session 10: Fasting and the Ketogenic Diet: The Next Therapies for Cancer Treatment and Prevention?

Leonora Renda, RDN | Oncology Outpatient Dietician, University of Arizona Cancer Center (Oncology Nutrition Dietetic Practice Group)

Michele Webb, CTR | Cancer Registry Coach, Sample Meadow

General Session 11: Keynote: Back to Purpose – The “Heart” of Healing

Publishing LLC, Registry Mindset, National Cancer Registrars

Lee Tomlinson | Medical Consultant, Professor, UCLA School of

Association

Continuing Education, F. Lee Tomlinson & Associates, Los Angeles,

General Session 5: CoC Pillar Survivorship Care Plan Case Studies Jacqueline Casillas, MD, MSHS | Associate Professor, UCLA School of Medicine, Associate Director, UCLA-Livestrong Survivorship Center of Excellence

2:45 - 3:30

10:45 - 11:45

(CE-certified activities)

General Session 4: CoC Pillar Quality Standard Case Studies

General Session 9: Impact of Oncology Prehabilitation and Rehabilitation Patti Frelund, RN-BSN, OCN, CBCN | Supervisor, Patient Navigator

Linda Bosserman, MD, FACP | Assistant Clinical Professor,

11:45 - 1

General Session 8: Moving Beyond Patient Satisfaction: Tips to Measure Program Impact (Survivorship & Navigation) Jennifer Klemp, PhD, MPH, MA | Assistant Professor, Cancer and

Gail Lindsay, RN | Managing Director of Clinical Program

Permanente Medical Group

Welcome (Recap of day before) Lillie D. Shockney, RN, BS, MAS

General Session 1: Metastatic Breast Program Lillie D. Shockney, RN, BS, MAS

Breakfast N.E.X.T. Session (non–CE-certified activity)

Welcome Lillie D. Shockney, RN, BS, MAS

8:30 - 9:30

6:45 - 8

(CE-certified activities unless otherwise noted)

General Session 6: CoC Pillar Patient Navigation Process Case Studies

11:45 - 12:45

California PM Session 12:45 - 1

Closing Remarks Lillie D. Shockney, RN, BS, MAS

* Agenda subject to change. Complete agenda and faculty information available at AonnOnline.org

Danelle Johnston, RN, MS, OCN, CBCN | Coordinator, Oncology Services at St. Jude Medical Center 3:30 - 4

General Session 7: CoC Pillar Psychosocial Distress Screening Case Studies Matthew J. Loscalzo, LCSW | Professor and Executive Director, Supportive Care, City of Hope National Medical Center

4 - 4:45

Commission on Cancer Panel Discussion Nina Miller, MSSW, OSW-C - Moderator | Cancer Liaison Initiatives

JOIN AONN+ FOR ITS 2015 WEST COAST REGIONAL MEETING May 18 - 20, 2015 at the Motif Seattle Hotel in Seattle, Washington.

Manager, American College of Surgeons, Commission on Cancer Michele Webb, CTR • Jacqueline Casillas, MD, MSHS • Danelle Johnston, RN, MS, OCN, CBCN • Matthew J. Loscalzo, LCSW 5:00 - 6:30

Reception (non–CE-certified activity)

REGISTER TODAY AT: AonnOnline.org/Regionals/West-Coast

Patient and Provider Access

Transforming Medicare Payments: Ambitious New Goals

By Leah Ralph, Manager, Provider Economics and Public Policy Association of Community Cancer Centers

T

here has been renewed focus in recent years on moving healthcare reimbursement from a system that incentivizes volume to one that incentivizes value. Largely an effort to rein in costs, particularly those related to Medicare, this trend has cropped up in every major healthcare law in the past decade, from the Medicare Modernization Act in 2003 to the Patient Protection and Affordable Care Act (ACA) in 2010. In fact, the ACA allocated $10 billion to the new Center for Medicare & Medicaid Innovation, whose purpose is to develop and test innovative ways to pay providers. Even last year’s bipartisan, bicameral sustainable growth rate legislation ultimately tied payment updates to participation in some form of alternative payment arrangement.

In January, though, for the first time in Medicare’s history, the US Department of Health & Human Services announced explicit goals for tying Medicare payments to alternative payment models and value-based payments. According to the agency, 30% of Medicare payments will be tied to alternative payment models such as accountable care organizations (ACOs), medical homes, and bundled payments for episodes of care by 2016. By 2018, 50% of payments will be tied to these models. The agency also set a goal of tying 85% of Medicare payments to quality or value by 2016 and 90% by 2018 through efforts such as the Hospital Value-­ Based Purchasing and Hospital Readmissions Reduction programs.

Perhaps most notable, the first benchmark is next year—an admirable but ambitious goal. The Obama administration is making this a priority, and we can expect to see an ac-

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celerated push to transition Medicare payments, and, in turn, private payer reimbursement. This shift is a huge undertaking, however, that will not

We urge the provider community to remain active participants in this dialogue to ensure that meaningful, realistic payment reform is achieved. only affect payments, but fundamentally change incentives for how providers deliver care. Implementation will take time and requires the right balance of forward momentum and critical safeguards to ensure that patients continue to receive the most appropriate quality care. As the US Department of Health & Human Services moves forward, the provider community should urge policymakers to continue to work toward consensus on appropriate quality measures; establish a sound, fair methodology for calculating financial benchmarks and risk adjustment; and allow providers the time, resources, and flexi-

Oncology Practice Management

I March 2015

bility they need to implement these new payment models.

Unlike primary care physicians, specialists will face unique challenges on how to fit into these new models.

The Centers for Medicare & Medicaid Services has placed a particular focus on oncology, funding a major community oncology medical home initiative, the COME HOME project, in 2012, and recently announced an oncology care model that will test the bundling of payments for chemotherapy administration. With other models (ie, Medicare’s Shared Savings Program) that are focused on primary care, however, it is still unclear how oncologists would be included or even participate. Caring for patients with cancer is complex and often expensive, leaving inherent challenges in how to account for cancer care in alternative models. How are high-cost drugs and innovative therapies treated in the construct of an ACO? Would high-cost treatments for patients with cancer be included in the financial benchmark? What is oncology’s role in shared risk and savings?

The Association of Community Cancer Centers (ACCC) and other organizations continue to work with the Centers for Medicare & Medicaid Services to answer these questions.

We urge the provider community to remain active participants in this dialogue to ensure that meaningful, realistic payment reform is achieved. One way to actively engage is by becoming more involved with ACCC. If you are interested in becoming a member, serving on a committee, attending one of our Oncology Reimbursement Meetings, or becoming more involved in advocacy, please e-mail me at lralph@accc-cancer.org. l

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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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Share Your StorY With uS!

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

Drug Coding Supplied by RJ Health Systems

FDA-Approved Medications Used for the Treatment of Multiple Myeloma The following sections will assist healthcare professionals and payers by providing appropriate coding and billing information associated with the treatment of multiple myeloma.

The following sections include: • Associated ICD-9-CM codes used for the classification of multiple myeloma • Drugs that have been FDA approved in the treatment of multiple myeloma • Drugs that are Compendia-listed for off-label use for multiple myeloma 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

Associated ICD-9-CM codes for the treatment of multiple myeloma: 203

Multiple myeloma and immunoproliferative neoplasms

The following fifth-digit subclassification is for use with category 203:

0 without mention of having achieved remission >Failed remission<

1 in remission

2 in relapse 203.0 Multiple myeloma

Kahler’s disease Myelomatosis Excludes: solitary myeloma (238.6) FDA approved for multiple myeloma

Generic (brand) name HCPCS code – code description arsenic trioxide (Trisenox)

J9017 – Injection, arsenic trioxide, 1 mg

betamethasone acetate J0702 – Injection, betamethasone and sodium phosphate acetate 3 mg and betamethasone (Celestone Soluspan) sodium phosphate 3 mg

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Compendia Possible CPT® off-label uses for administration multiple myeloma codes √

96413, 96415

√

11900, 11901, 20600, 20605, 20610, 96372

bortezomib (Velcade)

J9041 – Injection, bortezomib, 0.1 mg

√

96409

carfilzomib (Kyprolis)

J9047 – Injection, carfilzomib, 1 mg

√

96409

carmustine (BiCNU)

J9050 – Injection, carmustine, 100 mg

√

96413, 96415

cisplatin (Platinol-AQ)

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

cyclophosphamide (Cytoxan)

J8530 – Cyclophosphamide, oral, 25 mg

√

N/A

cyclophosphamide (Cytoxan)

J9070 – Cyclophosphamide, 100 mg

√

96409, 96413, 96415

dexamethasone (Decadron)

J8540 – Dexamethasone, oral, 0.25 mg

√

N/A

dexamethasone (Decadron)

J1100 – Injection, dexamethasone sodium phosphate, 1 mg

√

11900, 11901, 20600, 20605, 20610, 96372, 96374

Oncology Practice Management

I March 2015

√

96409, 96413, 96415

Drug Coding

doxorubicin HCl (Adriamycin)

J9000 – Injection, doxorubicin hydrochloride, 10 mg

doxorubicin HCl liposomal (Doxil)

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

epirubicin (Ellence)

J9178 – Injection, epirubicin hydrochloride, 2 mg

√

96409, 96413

etoposide (VePesid)

J8560 – Etoposide, oral, 50 mg

√

N/A

etoposide (Etopophos, Toposar)

J9181 – Injection, etoposide, 10 mg

√

96413, 96415

hydrocortisone (Solu-Cortef)

J1720 – Injection, hydrocortisone sodium succinate, up to 100 mg

√

96365, 96366, 96372, 96374

hydrocortisone (Cortef)

J8499* – Prescription drug, oral, nonchemotherapeutic, not otherwise specified

√

N/A

ifosfamide (Ifex)

J9208 – Injection, ifosfamide, 1 g

√

96413, 96415

interferon alfa-2b (Intron A)

J9214 – Injection, interferon, alfa-2b, recombinant, 1 million units

√

96372, 96401

interferon alfa-n3 (Alferon N)

J9215 – Injection, interferon, alfa-n3 (human leukocyte derived), 250,000 IU

√

11900, 11901

lenalidomide (Revlimid)

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

lomustine (CeeNU)

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

√

N/A

lomustine (CeeNU)

S0178 – Lomustine, oral, 10 mg

√

N/A

melphalan (Alkeran)

J8600 – Melphalan, oral, 2 mg

√

N/A

melphalan (Alkeran)

J9245 – Injection, melphalan hydrochloride, 50 mg

√

96409, 96413

methylprednisolone (Medrol)

J7509 – Methylprednisolone, oral, per 4 mg

√

N/A

methylprednisolone (Depo-Medrol)

J1020 – Injection, methylprednisolone acetate, 20 mg

√

11900, 11901, 20600, 20605, 20610, 96372

methylprednisolone (Depo-Medrol)

J1030 – Injection, methylprednisolone acetate, 40 mg

√

11900, 11901, 20600, 20605, 20610, 96372

methylprednisolone (Depo-Medrol)

J1040 – Injection, methylprednisolone acetate, 80 mg

√

11900, 11901, 20600, 20605, 20610, 96372

methylprednisolone (Solu-Medrol)

J2930 – Injection, methylprednisolone sodium succinate, up to 125 mg

√

96365, 96366, 96372, 96374

paclitaxel (Taxol)

J9267 – Injection, paclitaxel, 1 mg

√

96413, 96415

peginterferon alfa-2b (PegIntron)

J3590* – Unclassified biologics

√

96372

peginterferon alfa-2b (PegIntron)

S0148 – Injection, pegylated interferon alfa-2b, 10 mcg

√

96372

pomalidomide (Pomalyst)

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

√

96409 96413

√

N/A

√

N/A

√

Continued on page 50

March 2015

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www.OncPracticeManagement.com

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Drug Coding

FDA-Approved Medications... Continued from page 49 pomalidomide (Pomalyst)

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

prednisolone (eg, Millipred, Prelone)

J7510 – Prednisolone, oral, per 5 mg

√

N/A

prednisone (eg, Deltasone, Orasone)

J7506 – Prednisone, oral, per 5 mg

√

N/A

procarbazine (Matulane)

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

√

N/A

procarbazine (Matulane)

S0182 – Procarbazine hydrochloride, oral, 50 mg

√

N/A

teniposide (Vumon)

Q2017 – Injection, teniposide, 50 mg

√

96413, 96415

thalidomide (Thalomid) J8999* – Prescription drug, oral, chemotherapeutic, not otherwise specified topotecan (Hycamtin)

N/A

√

N/A

√

J9351 – Injection, topotecan, 0.1 mg

vinCRIStine (Vincasar PFS) J9370 – Vincristine sulfate, 1 mg

√

96413

√

96409

*When billing a nonclassified medication using a CMS 1500 claim form, you must include both the HCPCS code (eg, J8999 Revlimid) in Item 24D and the drug name, strength, and National Drug Code (NDC) in Item 19 or Item 24A (shaded area) in order to ensure appropriate reimbursement. Please note: Check with payer regarding correct placement of medication information.

References • Healthcare Common Procedure Coding System (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)

This information was supplied by

30 Cold Spring Road, Rocky Hill, CT 06067 T: (860) 563-1223 F: (860) 563-1650

www.RJHealthSystems.com

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Oncology Practice Management

I March 2015

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:

>> >> >> >> >> >> >> >> >>

ReimbursementCodes.com Drug Diagnosis Coding CMAC PartBorPartD.com NDC Conversion Database Min/Max Dosing Advisories Notations Clinical Consulting

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