OPM May 2015 Vol 5 No 4

www.OncPracticeManagement.com

May 2015

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Volume 5 • Number 4

Oncology Practice Management ™

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

340B Rules Remain in Flux

By Rosemary Frei, MSc

SGR Repealed, But the Work Is Just Beginning

By Gail Thompson

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he Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) was signed into law on April 16, making history not just by repealing the sustainable growth rate (SGR) formula for Medicare physician payment, but for the resounding bipartisan support of the legislation after decades of partisan posturing in the US

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Leah Ralph

ules surrounding implementation of 340B Drug Pricing, a government program that allows certain qualifying healthcare organizations to purchase reduced price outpatient medications, are in flux, according to a presentation at the recent Association of Community Cancer Centers 41st Annual Meeting in Arlington, VA. Offered through the US Department of Health & Human Services Health Resources and Services Administration (HRSA), the program is aimed at facili-

House of Representatives and Senate.

The House of Representatives approved the bill by a 392–37 vote, and the Senate followed a few weeks later with an approval vote of 92–8. These landslide votes were achieved by actual compromise on both the Democratic and Republican sides, which by itself is noteworthy.

Continued on page 8

The Nurse Practitioner’s Role in the Practice

By Peggy Barton, RN, Practice Administrator, Toledo Clinic Cancer Centers, Toledo, OH

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ewind about 5 years to 2010, and consider a few of the things that typically occurred in a medical practice: an infusion nurse sitting in the hall outside of an examination room, waiting for the physician to come out to answer a question about a patient. A triage nurse is lingering outside the

exam rooms waiting for the physician, and a stack of paperwork is sitting on the physician’s desk, awaiting completion. In another snapshot, tests for the physician to review remain untouched until

Continued on page 12

Continued on page 15 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 l a ia or P 30 r f a… t l ay om a W n ic er ela n d n M li c s U ith l a Tri w

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© 2015 Engage Healthcare Communications, LLC

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Table of Contents May 2015 • Volume 5 • Number 4

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

The Lynx Group President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Human Resources Jennine Leale Director, Strategy & Program Development John Welz Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistants Lora LaRocca Wayne Williams 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 Waiting for the Carrot? It May Take a While............................................ 6

By Dawn Holcombe, MBA, FACMPE, ACHE

Features Association of Community Cancer Centers Highlights 340B Rules Remain in Flux............................................................................ 1

By Rosemary Frei, MSc

Best Practices The Nurse Practitioner’s Role in the Practice.........................................1

By Peggy Barton, RN

Payment Reform SGR Repealed, But the Work Is Just Beginning........................................ 1

By Gail Thompson

Federal Government Outlines Stage 3 of Meaningful Use................. 10

By Rosemary Frei, MSc

Renal-Cell Carcinoma Sunitinib Associated with Higher Costs Compared with Pazopanib in Patients with RCC..................................................................... 14

By Chase Doyle 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.

May 2015

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Table of Contents May 2015 • Volume 5 • Number 4

Oncology Practice Management™, ISSN 2164-4403 (print), is published 10 times a year by Engage Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Copyright © 2015 by Engage Healthcare Communications, LLC. All rights reserved. Oncology Practice Management™ is a trademark of Engage Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or here­ after known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the publisher. Printed in the United States of America.

The ideas and opinions expressed in Oncology Practice Management™ do not necessarily reflect those of the editorial board, the editors, or the publisher.

Publication of an advertisement or other product mentioned in Oncology Practice Management ™ should not be construed as an endorsement of the product or the manufacturer’s claims.

Readers are encouraged to contact the manufacturers about any features or limitations of products mentioned.

Neither the editors nor the publisher assume any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material mentioned in this publication.

Oncology Practice Management ™

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

Continued from page 3

DEPARTMENTS Patient and Provider Access Rest in Peace, SGR..................................................................................... 18

By Leah Ralph

Wealth Management Seven Steps to Finding the Right Financial Advisor............................. 28

By W. Ben Utley, CFP, & Lawrence B. Keller, CFP, CLU, ChFC, RHU, LUTCF

Clinical Trial Tracker Trials Under Way for Patients with Melanoma...................................... 30 Drug Update Akynzeo (Netupitant and Palonosetron), a Dual-Acting Oral Agent, Approved by the FDA for the Prevention of Chemotherapy-Induced Nausea and Vomiting.................................. 34

By Lisa A. Raedler, PhD, RPh

Drug Coding FDA-Approved Medications Used for the Treatment of Leukemia................................................................................................. 46

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

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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

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

From the Editor

Waiting for the Carrot? It May Take a While

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

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he federal government is determined to shift Medicare’s traditional fee-for-service plans into alternative quality-based or value-based payment programs.

Currently more than 400 accountable care organizations (ACOs) and more than 100 hospitals and other healthcare groups accept Medicare bundled payments, but they are predominantly focused on primary care.

Medicare’s target is to shift about 30% of traditional payments to these alternative models by 2016, and about 50% by the end of 2018. In addition, Medicare wants to augment its spending with an incentive payment (eg, bonuses and penalties on top of traditional fee-for-service payments), with the goal of tying about 90% of Medicare spending to quality components by the end of 2018.

Those are good goals, and they read well in the press. However, many in the healthcare community will argue that Medicare is not set up to cover its costs, and that Medicare payments are often breakeven at best, especially for oncology practices. The goal of these Medicare alternatives is ultimately to reduce spending within the Medicare system, and to achieve savings over current spending levels.

Consequently, the details about compliance in these alternative programs are very important. The rewards are initially proving to be elusive, which does not bode well for the programs or their goals.

Physician groups like Healthfirst, an independent physician practice association in Burlington, VT, announced in January that its 40-physician ACO would be dropping out of Medicare’s Shared Savings Program (SSP). Despite keeping expenditures well below state and national averages and improving quality of care, the

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organization did not meet shared savings goals. Leaders indicated that after 2 years of participation, the program was unsustainable, and until the program is modified to recognize practices already providing low-cost, high-value care, it could not continue to participate.

Many in the healthcare community will argue that Medicare is not set up to cover its costs, and that Medicare payments are often breakeven at best, especially for oncology practices.

Thirteen of the 32 original health systems—nearly half—that joined Medicare’s Pioneer ACO program in 2011 have since dropped out. The Pioneer ACOs frequently cited as reasons the burden of compliance and the complexity of management and oversight, with some successes in quality-improvement measures and reduced readmission rates; however, almost half (14) failed to produce any cost-savings for which they could be

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rewarded. Participants who dropped out of the program reported in 2013 a willingness to pursue value-based programs, but no confidence in the Medicare program as the best way to move forward. Seven of the 9 that left in the first year moved into the Medicare SSP. The Medicare SSP has also yielded some improvements on quality measures, but only about a quarter of the 220 early participating ACOs qualified for bonuses for reductions in cost of care. Medicare has recently modified the SSP to reflect these challenges. Participants’ initial contracts expire at the end of 2015, at which point they must decide whether they will continue in the program.

At the end of 2014, Medicare proposed a rule change allowing ACOs to avoid the risk of nonperformance penalties for up to 6 years instead of the original 3 years.

Under the Affordable Care Act, Medicare has embarked on a number of new initiatives, hoping some of them will lead to the eventual solutions for healthcare reform. Initially, there is interest, but then the carrots (incentives) fail to materialize, and the sticks (penalties) hit—usually before the medical community is ready for them. These programs are often designed so that there will always be winners and losers, but is that a good incentive for those on the bottom of the scale? In 2013, more hospitals received penalties than rewards under Medicare’s Hospital Value-Based Purchasing program. That program reduced payment rates to all hospitals by 1.25%.

Those funds were set aside in a pot for incentive payments, but at the end of 2013, more than half of the hospitals did not receive enough payment to recoup the money that

From the Editor

was originally taken, leaving them with a net loss.

It is clear that, of all the programs that were started as a result of this new wave toward reform, not many are showing success. Physicians and hospitals are already in vulnerable financial situations, and elusive carrots of reform that ultimately do not materialize are not feasible incentives. Medicare sets very stringent rules, and then appears to define thresholds and benchmarks in ways that do not reflect the reality of the healthcare market.

In April 2015, large physician groups expressed concerns about the lack of quality bonuses being dispersed from the Centers for Medicare & Medicaid Services. These groups were early participants in Medicare’s Physician Feedback program/Value-Based Payment Modifier program that is intended to provide quality incentive bonuses to doctors—based on a list of more than 250 quality measures, 9 of which must be chosen for reporting. The program started payments in 2015 for 2013 performance by medical groups with ≥100 health professionals. In 2016, the program will start payments to groups of ≥10 health professionals based on 2014 performance. In the first year that groups are affected by the program, they can choose to forgo bonuses or penalties, but following that, the bonuses and penalties are mandatory. However,

few of the 1010 large physician groups to which the program applied this year are receiving bonuses, and 319 are now being penalized with a 1% reduction in Medicare payments.

This year, 564 of the 1010 groups opted out—most would have received penalties—but they will not have that option next year.

program, that the sticks are more prevalent than the carrots? At some point, will it have been useful to be a participant at the table, or will groups find that pursuing private payer projects and initiatives is more rewarding, with less financial risks and penalties?

Unfortunately, Medicare’s track record with value-based and quality-improvement programs does appear to embrace penalties more than it does rewards, which is likely driven by the planned design of reducing Medicare costs at any expense. This is perhaps an unrealistic view of the actual deliverables that are possible in the healthcare market. First and foremost, Medicare quality programs are cost-reduction programs, with a nod to quality improvement to the extent possible and a very shaky movement toward shared savings, which are proving to be more of a promise than a deliverable.

Let us not confuse this with solid progress toward value-based, quality care. Read between the lines carefully when considering participation, and be realistic in your assessments.

Does the program make sense if the shared savings do not materialize?

That is far more likely than what is promised. It may be that the current Medicare focus on “full speed ahead” could derail these programs after 2 to 3 years, which may leave healthcare in the United States in greater jeopardy than it is now. l

Read between the lines carefully when considering participation, and be realistic in your assessments.

Why is all of this important for oncology practices? Any physician practice with ≥10 professionals will be impacted by the physician value reporting program next year. In addition, Medicare has just launched (with great fanfare) a new Oncology Care Model, and practices have until the middle of June to submit applications for it. So far, the interest that has been generated seems to come from large health systems that incorporate both outpatient and inpatient care. Will promised shared savings targets, when announced, be realistic enough to justify the cost of participation? How many groups will find, 1 or 2 years into the

May 2015

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Payment Reform

SGR Repealed, But the Work Is... Continued from the cover “After more than a decade of uneven progress, it’s almost overwhelming to think that more than 90 percent of Congress finally voted to repeal the SGR,” said Rep Michael C. Burgess, MD (R, Texas), who sponsored the legislation. “With bipartisan strength, we passed the most meaningful entitlement reform in years with a product that’s a huge victory for seniors, providers, taxpayers, and the integrity of the entire Medicare system.”

Many details of the signed bill are yet to be defined, however, and will have a lasting and profound impact on healthcare delivery for decades.

The SGR formula calculation that was to have managed costs of medical care has been replaced by a modest 0.5% annual payment update for the next 5 years for all physicians, as well as a merit-based incentive payment system (MIPS) for all physician payments beginning January 1, 2019.

MIPS payments will be based upon measures and criteria that are yet to be defined. The secretary of the Department of Health & Human Services is tasked under the law to “assess appropriate adjustments to quality measures, resource use measures, and other measures used under the MIPS; and…assess and implement appropriate adjustments to payment adjustments, composite performance scores, scores for performance categories, or scores for measures or activities under the MIPS.” The legislation calls for performance assessments in 4 key areas:

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quality of care, resource use, clinical practice improvement (including expanded practice access, population management, care coordination, beneficiary engagement, and patient safety and practice assess-

“With bipartisan strength, we passed the most meaningful entitlement reform in years with a product that’s a huge victory for seniors, providers, taxpayers, and the integrity of the entire Medicare system.”

—Rep Michael C. Burgess, MD (R, Texas)

ment improvement activities), and the meaningful use of certified electronic health record (EHR) technology. It also extends the Children’s Health Insurance Program and the Maternal, Infant, and Early Childhood Home Visiting program, and continues certain assistance programs for qualifying Medicare and Medicaid beneficiaries.

Next Steps Medicare has to adjust the payment rates in its systems to reflect the final law; however, Medicare assures practices that it will continue to process claims on a timely basis and that any claims that may have been pro-

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cessed with the SGR-driven 21% reduction in physician payments will be reprocessed. New and final 2015 rates will be applied and payments adjusted without further action needed by the physician practices.

Congress and the Centers for Medicare & Medicaid Services (CMS) have not yet begun to elaborate on how the new value-based payment models will transition, or how the new alternative payment mechanisms will work. Bundled payment initiatives already are being explored, but with mixed results. Some CMS alternative model pilots have seen mixed success, with both reported savings as well as a number of participants dropping out, citing concerns for their continued financial viability based upon the costs of participating in comparison to the financial return.

Pundits are expressing concern about the final direction of the MACRA legislation, warning that it will force doctors into hospital-run accountable care organizations with rules decreed by the federal government. Other concerns center on the lack of credible quality measurements for physicians.

Going forward, as CMS moves to new definitions of value in healthcare, it is clear from ongoing reform initiatives that there will be both winners and losers. Discussions to define the intent and execution of the MACRA legislation will continue, and providers should remain vigilant to monitor developments regarding this legislation as well as key details that are not yet finalized. l

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Payment Reform

Federal Government Outlines Stage 3 of Meaningful Use

By Rosemary Frei, MSc

C

riteria for Stage 3 of Meaningful Use was announced and published at the end of March, detailing benchmarks that eligible providers and hospitals will have to meet to qualify for certain incentive payments and avoid reimbursement penalties. The proposed ruling by the US Department of Health & Human Services and the Centers for Medicare & Medicaid Services (CMS) outlines a framework that is in some ways more flexible and in others more rigid than Stage 1 and Stage 2.

“These changes…support our broader efforts to increase simplicity and flexibility in the program while driving interoperability and a focus on patient outcomes in the meaningful use program,” according to a summary of the proposed rule.

As part of Stage 3, providers will need to attest to 2 of 3 measures associated with each of the main categories of Meaningful Use: coordi­nation of care through patient engagement, health information exchange, and public health reporting. Providers may continue to use 2014 edition electronic health record (EHR) technology through 2017. There are still exceptions for providers in rural areas or who practice at more than 1 location, as well as for lack of availability of Internet access, newly practicing providers and hospitals, and unforeseen circumstances such as natural disasters.

In addition, the thresholds of most measures have been increased, such as having to use computerized provider order entry (CPOE) systems for >80% of all prescriptions (up from 50% in Stage 2), >60% of all laboratory test orders, and >60% of diagnostic imaging orders. Furthermore, Stage 3 also requires that >80% of all patients

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seen by a provider or discharged from a hospital or emergency department have access to their health information within 24 hours of its availability to the provider.

Compliance with Stage 3 requirements will be optional for providers in 2017, but mandatory for all eligible providers starting in 2018 regardless of previous participation in Stage 1 or Stage 2. CMS also intends Stage 3 to be the last stage of Meaningful Use.

The proposed ruling outlines a framework that is in some ways more flexible and in others more rigid than Stage 1 and Stage 2.

“The incorporation of the requirements into one stage for all providers is intended to respond to stakeholder input regarding the complexity of the program, the success of certain measures which are part of the meaningful use program to date, and the need to set a long-term, sustainable foundation based on a consolidated set of key advanced use objectives for the Medicare and Medicaid EHR Incentive Programs,” according to the executive summary.

Other key conditions in Stage 3, in addition to the raised thresholds described previously, include the following: • Reporting for a full calendar year starting in 2017 for nearly all providers instead of 90 days • Successfully meeting the criteria associated with each of 8 specified

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program objectives (protect patient health information, electronic prescribing, clinical decision support, CPOE, patient electronic access to their health information, coordination of care through patient engagement, health information exchange, and public health and clinical data registry reporting); in measures with 3 subsets, achieving at least 2 of the 3 • Using secure messages via the electronic messaging function of EHRs to communicate with more than 35% of patients • For more than 40% of new patients and for more than 50% of existing patients being transitioned to other care facilities or providers, creating a summary of the care record in the EHR and sending it electronically to the new providers/facilities.

The executive summary states that the “stage 3 proposed rule would… focus on the advanced use of EHR technology to promote improved patient outcomes and health information exchange.…[It also] would further support efforts to align the EHR Incentive Programs with other CMS quality reporting programs that use certified EHR technology, such as the Hospital Inpatient Quality Reporting (IQR) and Physician Quality Reporting System (PQRS) programs, as well as continue alignment across care settings for providers demonstrating meaningful use.”

CMS has given providers and other stakeholders 2 months to submit comments regarding this rule from the date the rule was published.

Comments and feedback are due by May 29 and can be submitted by visiting www.regulations.gov and referring to file code CMS-3310-P. l

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Association of Community Cancer Centers Highlights

340B Rules Remain in Flux Continued from the cover ties such as Medicare/Medicaid Disproportionate Share Hospitals, children’s hospitals, safety net providers, and entities that help to treat a high number of uninsured or indigent patients. Although the program has been active for more than 20 years, it continues to try to navigate the cross-currents between key stakeholders and clearly define parameters and requirements.

“HRSA has really struggled to provide clear instructions,” said Leah Ralph, Manager, Provider Economics and Public Policy, Association of Community Cancer Centers.

“We need clear definitions about what a patient is, what a covered entity is, to be sure that our members can remain compliant with the 340B program.”

The program was created by Congress in 1992 and has grown rapidly ever since, rising by 2013 to 23,745 participating hospitals and other covered entities. Current problems stem from the fact that the program does not have a requirement that a person be uninsured to access discounted drugs, explained Ms Ralph.

A provider with covered-entity status can provide discounted drugs to any patient in the outpatient setting.

In 2010, HRSA attempted to narrow the patient definition, but it withdrew the revised definition under pressure from covered entities, she said. Next, guidance was expected from HRSA in July and then November 2014 that would have clarified the definitions of eligibility of patients, hospitals, and off-site facilities, and also spelled out compliance requirements for contract-­ pharmacy arrangements. However, HRSA thus far has not released a ruling, said Ms Ralph.

The delay has been due to court battles between covered entities, Congress, and proponents of the Patient Protection and Affordable Care

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Act (ACA), which have sought to expand access to 340B, versus pharmaceutical companies, which are seeking a more limited definition of patients covered by the program, explained Ms Ralph. She said this push–pull is best illustrated by the orphan drug exclusion in legislation that enacted the ACA.

“We need clear definitions about what a patient is, what a covered entity is, to be sure that our members can remain compliant with the 340B program.”

—Leah Ralph

When the ACA was passed into law it added to the 340B program 4 new covered-entity types, including certain freestanding cancer hospitals, and also exempted orphan drugs from having to be provided by manufacturers at the 340B discount.

HRSA then ruled that this exclusion applies only to orphan drugs when they are used for the drugs’ orphan-disease indications, which severely limited the exemption, said Ms Ralph.

The Pharmaceutical Research and Manufacturers of America (PhRMA) fought this limitation of the exemption and won; in May 2014, a judge in a US District Court in Washington, DC, invalidated it on the grounds that HRSA lacks the authority to issue a regulation on the treatment of orphan drugs in the 340B program. That called into question HRSA’s authority to issue regulations on the implementation of the 340B program, said Ms Ralph.

As a result, the agency withdrew a

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mega-guidance it was preparing.

HSRA is now expected to release this guidance in June 2015.

Meanwhile, HRSA in July 2014 issued an interpretive rule that adopted the orphan drug exclusion.

However, the Department of Justice quickly filed a brief saying the interpretive rule is not binding, and, in October 2014, PhRMA filed a lawsuit challenging the interpretive rule, Ms Ralph recounted. What lies ahead is unclear, she said. Congress could codify HRSA’s interpretive rule and pass it as law, although this is unlikely to happen, according to Ms Ralph. Furthermore, a Government Accountability Office report on the 340B program is expected in mid-2015 and may prompt some action.

HRSA is continuing to develop proposed rules to implement minor provisions required by the ACA. These include rules for establishing manufacturer penalties for knowingly overcharging covered entities, and for the calculation and validation of the 340B ceiling price—both originally expected in April 2015 but not yet released at the end of that month—as well as for processes to resolve claims by manufacturers and covered entities, and to have manufacturers issue refunds to covered entities for overcharges.

Ms Ralph said, “What really needs to be done for this program” is for HRSA to provide clearer definitions of eligible patients and covered entities and also methods to improve the program. Tracking of trends in the healthcare system that impact the 340B program would also be helpful, she noted.

“We’ll compare that to what will probably [actually] happen,” she concluded. “There will be continued litigation by PhRMA, more audits to verify the eligibility of covered entities—and hopefully more clarity.” l

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Renal-Cell Carcinoma

Sunitinib Associated with Higher Costs Compared with Pazopanib in Patients with RCC

By Chase Doyle

Hollywood, FL—Sunitinib and pazopanib have long battled for supremacy in treating advanced renal-cell carcinoma (RCC). According to findings presented at the 2015 National Comprehensive Cancer Network (NCCN) conference, the newer drug, pazopanib, may have some advantage in terms of total cost of care, but survival outcomes were exactly the same.

An independent study from Humana comparing costs and health outcomes in initial therapy for RCC showed that sunitinib had a $12,000 higher mean total cost of care than pazopanib.

“Survival and treatment characteristics were similar for both index medications, but medication and total healthcare costs trended higher with sunitinib treatment, despite higher preindex total costs in the pazopanib group,” said co-investigator Laura E. Happe, PharmD, MPH, Strategic Consultant, Humana, Louisville, KY. “Nonadherence with sunitinib was associated with significantly higher total healthcare costs, which may indicate unfavorable tolerability with sunitinib treatment.” She emphasized that this is a hypothesis that was not proved in this study.

Sunitinib and pazopanib are 2 tyrosine kinase inhibitors (TKIs) approved by the FDA as first-line options for the treatment of patients with advanced RCC; clinical evidence and national guidelines do not differentiate between these therapies. Two comparative cost studies based on data from the COMPARZ and PISCES trials showed that pazopanib was less costly and more cost-effective than sunitinib, but these findings were based solely on clinical trial data.

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First Real-World Comparison “To our knowledge,” said Dr Happe, “this is the first head-to-head comparison of these 2 TKIs in a real-world setting. We are looking at our Humana global universe of millions of lives.

This study was not funded by either manufacturer…which makes it a very unique analysis.”

The study was an observational retrospective cohort with up to 12 months of follow-up.

The study was an observational retrospective cohort with up to 12 months of follow-up for 241 patients receiving sunitinib and 112 receiving pazopanib for at least 6 months.

Treatment interruptions were defined as therapy gaps >30 days. Adherence was quantified using proportion of days covered, which was calculated as days prescribed divided by total days of follow-up.

“We saw no difference in overall survival, which supports the COMPARZ trial,” said Dr Happe. “About 55% of patients remained alive after 1 year. Treatment interruptions and adherence were also the same. From everything we can garner from claims, in terms of efficacy, the drugs were the same.”

Treatment Cost Comparison The investigators examined the mean total healthcare costs, broken down by component medical and pharmacy costs and stratified by adherent status.

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“Total costs were the same,” Dr Happe reported. “Sunitinib was higher numerically ($76,624 vs $64,432), but this was a nonsignificant trend. The only component approaching statistical significance was pharmacy index medication, which reflects the price of the drug.

Sunitinib was $5000 more expensive ($26,984 vs $21,404)….All other costs were the same.”

Although not statistically significant, pazopanib was numerically less expensive in total medical and pharmacy costs.

According to Dr Happe, one of the study’s most interesting findings was the significant difference in costs between drugs within the nonadherent subgroup. These were $82,730 for sunitinib and $65,040 for pazopanib (P = .01), she reported.

One suggestion for this difference was a possible increase in side effects with sunitinib, leading to greater cost of care.

“We don’t know what’s driving this difference in cost,” acknowledged Dr Happe. “Clinical trials have shown some differences in tolerability, meaning sunitinib may be less tolerable than pazopanib.”

Given the lack of difference in efficacy between sunitinib and pazopanib by NCCN or clinical trials, the higher costs of sunitinib will be an important consideration in choice of treatment, the investigators of this study concluded.

“We validated no clinical difference between these drugs,” said Dr Happe. “And from a medical standpoint, you are only looking at the price of the drug. If your health plan gets a good discount on one of these drugs, you might consider these drugs interchangeable.” l

Best Practices

The Nurse Practitioner’s Role... Continued from the cover he or she has time—usually at the end of the day—to specify to staff members what needs to be done.

Fast forward to the present, and all of that has changed. In a growing part of oncology practices, nurse practitioners (NPs) are applying their nursing expertise to both clinical and management roles, and helping to streamline procedures and develop more efficient protocols in oncology care. When an NP is on vacation, you can be assured that a doctor will be looking for him or her, because the doctor is dealing with patient care issues that the NP has largely assumed. In our practice, NPs are critical members of the management and patient care team, serving as physician extenders by contributing essential skill sets and performing key roles (Table).

The concept of physician extenders in an oncology practice has evolved over time. More than 10 years ago, Elaine Towle, CMPE, spoke at a medical society meeting about how an NP and physician assistant (PA) were being used at her New Hampshire practice. The team was using the PA and NP as extenders not only to see patients during follow-up visits, but to supervise chemotherapy administration. Payers were reimbursing the practice for these visits, and the practice was able to address chemotherapy scheduling problems that occurred when the doctor was not present in the suite.

an NP could also provide coverage for the infusion room. Our practice has multiple satellite offices, and the ability to provide infusion services on days when a physician was not in the suite was of interest from the standpoint of continuity of care, as well as from the standpoint of improved staff efficiency. The year was 2002, and at that point in time, the physicians were not keen on having the NP see their follow-up patients, but they were very interested in expanding the number of days that chemotherapy was administered.

With the NP in the office, this became possible. So the question was where and how do we start?

We needed an NP who would have immediate credibility with the doctors. Fortunately, one of my nursing school colleagues was the ideal candidate. Not only was she an NP, but she also came with intensive care nursing experience. She had set up the oncology unit and infusion center at one of the hospitals she worked at, served as manager for the service, and became the clinical nurse specialist. In that role, she developed programs and trained new staff nurses. She then went on to become an NP, moving from oncology to family practice.

Even though she had been out of oncology for a few years, she had credibility among the physicians and nurses in the practice. With this one hire, we obtained an oncology provider who was experienced, and who had management and program development expertise. The real challenge was to convince her that she was the ideal candidate to develop this new role in a practice. Her management and program development skills were critical to the implementation of the NP role; however, there was no job description, no real definition of what the role would be, and no guarantee that it would continue.

In our practice, NPs are critical members of the management and patient care team, serving as physician extenders by contributing essential skill sets and performing key roles.

—Peggy Barton, RN

The concept intrigued me, and I began an investigation into how we could use an NP in our own practice.

Background Initially, the use of physician extenders was not a concept that interested our physicians; it was not until we completed an analysis of how an NP could benefit the practice that there was interest. We learned that

Table Nurse Practitioner Roles and Responsibilities Role

Responsibility

Management

Serve as chief nursing officer or an office supervisor

Clinical

Provide hospital-based (oncology hospitalist) and office-based (care provider, triage, and patient education) services

Program development

Implement new services and facilitate staff development

Navigation

Guide patients along the care continuum within the practice

Continued on page 16

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Best Practices

The Nurse Practitioner’s Role... Continued from page 15 It was a gamble on her part. All she had was my belief that the oncology NP was going to play a significant role in the future of cancer care. I am grateful every day that she decided to take the chance.

The physicians agreed to fund the position in 2002, and she was hired.

She started in a clinical role, primarily covering chemotherapy infusions when the physicians were not in the suite. She was not assigned to one specific office, and moved from office to office. In doing so, the registered nurses (RNs) in those offices learned to rely on her to help them with all sorts of patient care issues. Fortunately for us, our NP was someone who did not require a lot of direction and who was very comfortable in all of our offices. Although at times she got tired of moving from one office to another, she did not need to be assigned to just one office. She rarely worked in an office for the entire day, and working in a single office for a whole week simply did not happen.

She was the plug person, filling in when a doctor was on vacation or covering a morning or afternoon when a physician was not going to be in the office. Because of her, we were able to open up additional office hours, which greatly enhanced our ability to provide consistent care to the patients. Often, she would be working in an office but get a call from another office about a patient care problem.

Initially, our NP did not have a full schedule of patients, but that started to change as several physicians began to realize that she could provide excellent follow-up care while they focused on new consults and patients who needed changes in therapy.

With this came the realization that we could use more help in the NP role. We began adding NPs to work with physicians in our satellite offices, and with these additions came

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differentiation of the NPs’ roles in our practice (Table). Today, we have NPs providing clinical services and assuming management responsibilities in our operation. We also have NPs who are responsible for developing and implementing new services in the practice. This diversity in the role is attractive to NPs who have interests beyond clinical services.

One of the benefits of having a diverse group of NPs is the various backgrounds and experiences they bring to their positions.

Clinical Role The clinical role is the foundation of the NP’s role in our practice. One of the benefits of having a diverse group of NPs is the various backgrounds and experiences they bring to their positions. We have several NPs with critical care backgrounds, which is useful when there is a crisis in the infusion room. We also have NPs with a strong primary care background, which is helpful when they are managing the comorbid conditions that our patients often have.

The family practice background helps NPs develop a schedule that is efficient, but also provides enough time for question-and-answer sessions with patients and their families. We have an NP who has a pal­ liative care background, which is helpful in the development of endof-life programs.

The clinical role is office-based as well as hospital-based. We have several NPs who have a combined hospital-rounding role and an office schedule. For the NPs in this role,

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continuity of care is important.

These NPs see patients in the hospital and then can see them during their posthospital visits to the office.

It is an important care coordination and navigator function.

The NPs who are exclusively office-based are important navigators of care within the office. They communicate with the doctors about the patient’s plan of care, and then work with the staff to ensure that the plan is implemented. These NPs handle triage in the office, and are the go-to people for all patient care issues. The physicians have noticed a significant reduction in the number of interruptions in their schedules. The NPs review test results and consult with physicians as necessary prior to communicating with the patients and their families. In Ohio, where our practice is based, NPs can order select narcotics, so pain management and other supportive care medications are ordered based on patient needs. With the addition of an in-office dispensary, the NPs are able to provide supportive care medications needed for a regimen at the time of the patient’s appointment. Patients leave the office not only with information, but with medications needed to support them at the start of their treatment plan.

Another important clinical role is the hospital-based NP. NPs who make hospital rounds function as hospitalists for the practice in hospitals with which we are affiliated, and collaborate with the rounding phy­ sician to manage new-patient consults, orders, and assessments for the practice’s patients. The transition of care from office to hospital, hospital to office, or hospital to home or hospice is handled by this NP. In recent months, an RN has started providing rounding support as well.

Another responsibility that the NPs assume in the offices is that of

Best Practices

triage. In the past, this was done by RNs; however, an evaluation of how to improve productivity and reduce physician interruptions led to us changing this to an NP responsibility. This is an important responsibility, and provides substantial support to the office phone staff. Further development of the role will include identifying what has been directed to an NP that could be more efficiently handled by an RN or licensed practical nurse.

Management Role Not everyone is content with a purely clinical role. For some NPs, management opportunities are essential for their growth and development. Managing a large group practice with multiple satellite offices is difficult without assistance. Our NPs provide support as office supervisors, and each supervisor is responsible for the personnel management in his or her office. NPs who assume this responsibility are in a unique position to improve patient flow and productivity.

These supervisors need support from an experienced manager, and because of her past experience, our very first NP assumed the role of the chief nursing officer and NP team supervisor. Not only did she have the required management experience, but she also understood the needs of different members of the staff. She conducts quarterly NP meetings, hires and evaluates new NPs, and ensures that a proper orientation is completed and that areas for development are addressed. She is also responsible for the productivity of each NP, and provides feedback to each NP related to this. In this role she is also responsible for the clinical operations of the practice. She has been instrumental in the initiation of the American Society of

the data to assess the need for intervention. It is nice to see that other organizations today understand the importance of mental health, distress screening, and the impact of depression on response to therapy.

Another area where the NPs help in program development has been with the initiation of our in-office dispensing service. The NPs helped outline the way oral chemotherapy dispensing would be monitored, and set up patient teaching visits. These visits are initiated for every patient before the start of a new chemotherapy order, whether it is an injected or oral medication. The NP reviews the treatment plan, answers any questions the patient and family may have, orders supportive care drugs, and provides the patient with treatment and follow-up visit appointments.

The NPs also integrated patient follow-up as an important component for ensuring patient compliance with an oral treatment plan. This was done before we had a dispensing pharmacy. The processes that were initially set up for interacting with a specialty pharmacy have now been integrated into our own dispensing process. Again, we have seen that we are ahead of the curve with regard to care management of these patients.

During our QOPI recertification process, our surveyor complimented our practice’s process, and we were asked to be a resource for other practices.

Clinical Oncology Quality Oncology Practice Initiative (QOPI) audits, QOPI certification and recertification, and planning for certification by the National Committee for Quality Assurance as a Patient-Centered Specialty Practice.

Program Development Although management is not for everyone, some NPs are able to use their skills and expertise to serve as role models for all staff members in a practice. These NPs see needs and are interested in developing services to meet those needs.

Our NPs provide support as office supervisors, and each supervisor is responsible for the personnel management in his or her office.

One of our NPs was very interested in using continuous quality improvement processes to begin changing the way we deal with depression and patient distress in the practice.

She became involved in a Michigan Society of Hematology and Oncology–sponsored quality initiative to ensure that we were conducting initial and ongoing assessments of the emotional status of our patients.

Drawing on her skills as an educator, she evaluated the assessment tools, conducted training sessions with staff on how to administer the tool, and oversaw the implementation of this important component of care.

We were ahead of the curve with this idea. Today we have survey tools on many of our charts, and we use

Conclusion The addition of NPs has added important elements to improve practice operations. They provide clinical services in our offices, and see patients at routine follow-ups and in the infusion suite. They are nursing leaders, provide direction and support to the clinical staff, and serve as role models throughout the practice. l

Oncology Practice Management is now available online at: www.OncPracticeManagement.com

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Patient and Provider Access

Rest in Peace, SGR

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

R

ecent months have brought unprecedented momentum on an issue physicians and Congress have been struggling with for more than a decade: repealing the sustainable growth rate (SGR) formula. On April 14, after 18 years of wrangling and 17 short-term patches to ensure that cuts to Medicare’s physician payment rates would not go into effect, Congress finally passed a permanent overhaul of the SGR— the flawed formula created by the Balanced Budget Act of 1997 that calls for draconian cuts to physician payment rates when Medicare spending exceeds a certain target.

This was quite an accomplishment for Congress, which has struggled for years to develop the policy around— and pay for—a permanent fix. Physicians are applauding the long-overdue legislation for finally providing the predictable, appropriate payments they need to continue to provide high-quality care.

As are most things related to the SGR, getting to a permanent solution was not an easy road. Most recently, just days before the current SGR patch expired, and right before Congress’ Easter recess, the US House of Representatives overwhelmingly passed H.R. 2, known officially as the Medicare Access and CHIP Reauthorization Act. The US Senate was expected to take up the House bill, but, in keeping with the political brinksmanship Congress has employed with the SGR, on March

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27 the chamber recessed for 2 weeks, leaving a very small window to consider the bill when its members returned on April 13. Meanwhile, the patch that had been enacted in 2014 expired this year on March 31, and

Physicians are applauding the longoverdue legislation for finally providing the predictable, appropriate payments they need to continue to provide high-quality care. the Centers for Medicare & Medi­ caid Services indicated that it would hold physician claims through April 15 to give the Senate time to reconvene and consider the bill.

Prospects for passage of the legislation looked good, but uncertainty

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remained. Republicans opposed the price tag, as only a third of the $214billion bill was offset. Democrats wanted a longer reauthorization of the CHIP program (included in the bill) and opposed increased means testing and other provisions that would require Medicare beneficiaries to pay more. But by a Senate vote of 92-8, the legislation made it across the finish line.

The bill will permanently replace the SGR formula with stable payment updates through 2019, after which rates will stabilize during a 5-year transition period, from 2020 to 2025. Beginning in 2019, physicians will either transition to the newly created merit-based incentive payment system, which will reward doctors with higher reimbursements based on better overall performance under fee-for-service (FFS), or will participate in alternative payment models under which doctors move away from traditional FFS toward payments based on quality and value of care. H.R. 2 builds on last year’s bipartisan, bicameral compromise.

Upon passage of the bill in the House, Rep Michael Burgess, MD (R-Texas), the bill’s lead sponsor, said “this is the work of a collaborative body…it is time to end the SGR. Let us never speak of this issue again.” So, we can finally say good riddance to the SGR, but now we must turn to what the bill means for the future of Medicare reimbursement. Stay tuned. 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 5.2 MONTHS IMPROVEMENT IN MEDIAN OVERALL SURVIVAL

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

compared with placebo plus prednisone.

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 [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function. *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. 2015 3/15 029979-150220

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

B:11.125 in

003307-150130

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 enzymes CYP2D6 and CYP2C8. Avoid co-administration with CYP2D6 substrates with a narrow therapeutic index. If alternative treatments cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate drug. In a CYP2C8 drug interaction trial in healthy subjects, the AUC of pioglitazone, a CYP2C8 substrate, was increased by 46% when administered with a single dose of ZYTIGA®.

Patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA®.

Use in Specific Populations—Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C). †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 ≥2.5 XULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT >5X ULN. Table 1 shows adverse reactions on the ZYTIGA arm in Study 1 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with ZYTIGA was 8 months.

Table 1: Adverse Reactions due to ZYTIGA in Study 1 ZYTIGA with Placebo with Prednisone (N=791) Prednisone (N=394) 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 Musculoskeletal and Connective Tissue Disorders: myopathy, including rhabdomyolysis DRUG INTERACTIONS Drugs that Inhibit or Induce CYP3A4 Enzymes: Based on in vitro data, ZYTIGA is a substrate of CYP3A4.

In a dedicated drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) in full Prescribing Information].

In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone [see Clinical Pharmacology (12.3) in full Prescribing Information].

Effects of Abiraterone on Drug Metabolizing Enzymes: ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. In

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine).

If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3) in full Prescribing Information].

In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate.

Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA [see Clinical Pharmacology (12.3) in full Prescribing Information].

For patients who develop hepatotoxicity during treatment, interruption of treatment and dosage adjustment may be required [see Dosage and Administration (2.2) in full Prescribing Information, Warnings and Precautions, and Clinical Pharmacology (12.3)] in full Prescribing Information.

Patients with Renal Impairment: In a dedicated renal impairment trial, the mean PK parameters were comparable between healthy subjects with normal renal function (N=8) and those with end stage renal disease (ESRD) on hemodialysis (N=8) after a single oral 1,000 mg dose of ZYTIGA. No dosage adjustment is necessary for patients with renal impairment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

OVERDOSAGE Human experience of overdose with ZYTIGA is limited.

There is no specific antidote. In the event of an overdose, stop ZYTIGA, undertake general supportive measures, including monitoring for arrhythmias and cardiac failure and assess liver function.

Storage and Handling: Store at 20°C to 25°C (68°F to 77°F); excursions permitted in the range from 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature].

Based on its mechanism of action, ZYTIGA may harm a developing fetus.

Therefore, women who are pregnant or women who may be pregnant should not handle ZYTIGA without protection, e.g., gloves [see Use in Specific Populations].

PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information) • Patients should be informed that ZYTIGA and prednisone are used together and that they should not interrupt or stop either of these medications without consulting their physician.

• Patients receiving GnRH agonists should be informed that they need to maintain this treatment during the course of treatment with ZYTIGA and prednisone.

• Patients should be informed that ZYTIGA must not be taken with food and that no food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. They should be informed that the tablets should be swallowed whole with water without crushing or chewing. Patients should be informed that taking ZYTIGA with food causes increased exposure and this may result in adverse reactions.

• Patients should be informed that ZYTIGA is taken once daily and prednisone is taken twice daily according to their physician’s instructions.

• Patients should be informed that in the event of a missed daily dose of ZYTIGA or prednisone, they should take their normal dose the following day. If more than one daily dose is skipped, patients should be told to inform their physician.

• Patients should be apprised of the common side effects associated with ZYTIGA, including peripheral edema, hypokalemia, hypertension, elevated liver function tests, and urinary tract infection. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION. • Patients should be advised that their liver function will be monitored using blood tests.

• Patients should be informed that ZYTIGA may harm a developing fetus; thus, women who are pregnant or women who may be pregnant should not handle ZYTIGA without protection, e.g., gloves. Patients should also be informed that it is not known whether abiraterone or its metabolites are present in semen and they should use a condom if having sex with a pregnant woman. The patient should use a condom and another effective method of birth control if he is having sex with a woman of child-bearing potential. These measures are required during and for one week after treatment with ZYTIGA.

USE IN SPECIFIC POPULATIONS Pregnancy: Pregnancy Category X [see Contraindications].: ZYTIGA can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no adequate and well-controlled studies with ZYTIGA in pregnant women and ZYTIGA is not indicated for use in women, it is important to know that maternal use of a CYP17 inhibitor could affect development of the fetus. Abiraterone acetate caused developmental toxicity in pregnant rats at exposures that were lower than in patients receiving the recommended dose. ZYTIGA is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with ZYTIGA. In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6-17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients.

Nursing Mothers: ZYTIGA is not indicated for use in women. It is not known if abiraterone acetate is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZYTIGA, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness of ZYTIGA in pediatric patients have not been established.

Geriatric Use: Of the total number of patients receiving ZYTIGA in phase 3 trials, 73% of patients were 65 years and over and 30% were 75 years and over. No overall differences in safety or effectiveness were observed between these elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients with Hepatic Impairment: The pharmacokinetics of abiraterone were examined in subjects with baseline mild (N=8) or moderate (N=8) hepatic impairment (Child-Pugh Class A and B, respectively) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone after a single oral 1,000 mg dose of ZYTIGA increased by approximately 1.1-fold and 3.6-fold in subjects with mild and moderate baseline hepatic impairment, respectively compared to subjects with normal hepatic function.

In another trial, the pharmacokinetics of abiraterone were examined in subjects with baseline severe (N=8) hepatic impairment (Child-Pugh Class C) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of abiraterone increased by approximately 7-fold and the fraction of free drug increased 2-fold in subjects with severe baseline hepatic impairment compared to subjects with normal hepatic function.

No dosage adjustment is necessary for patients with baseline mild hepatic impairment. In patients with baseline moderate hepatic impairment (ChildPugh Class B), reduce the recommended dose of ZYTIGA to 250 mg once daily. Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C). If elevations in ALT or AST >5X ULN or total bilirubin >3X ULN occur in patients with baseline moderate hepatic impairment, discontinue ZYTIGA treatment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

Manufactured by: Patheon Inc. Mississauga, Canada Manufactured for: Janssen Biotech, Inc. Horsham, PA 19044 ©Janssen Biotech, Inc. 2012 Revised: January 2015 028959-150203

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Wealth Management

Seven Steps to Finding the Right Financial Advisor

By W. Ben Utley, CFP, and Lawrence B. Keller, CFP, CLU, ChFC, RHU, LUTCF

W. Ben Utley

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Lawrence B. Keller

s a physician with substantial income (or income potential), you will most likely be contacted by a number of individuals offering various types of financial products and services throughout your career. If you are in the market for an advisor, you will want to know the qualifications and experience level of each one you are considering. Unlike medicine, which has a standardized path that physicians must take to gain the education, training, and experience necessary to obtain board certification, the insurance and financial services industry does not. While advisors must pass certain tests to earn a license in securities or insurance, for the most part, anyone can call himself or herself a financial advisor.

Credentials and Certifications Finding the right financial advisor to help you build your financial future can be as challenging as choosing the right doctor to care for your health, so it is important to look for several key credentials. Following is a brief summary of some of the most recognizable designations or certifications that you might see among financial service professionals and what it takes to earn them.

Certified Public Accountant (CPA): CPAs provide you with advice on tax matters and help you prepare and

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submit your income tax returns to the Internal Revenue Service. To be a CPA, candidates must pass a 14hour computer-based test with 4 sections: auditing and attestation; financial accounting and reporting; regulation; and business environment and concepts. There are also work experience requirements that must be met. Not all accountants are CPAs. CPAs must meet stringent continuing education requirements and are regulated by states as well as their professionâ&#x20AC;&#x2122;s code of ethics.

Personal Financial Specialist (CPA/ PFS): A PFS is a CPA who has demonstrated both knowledge and significant practical experience in the area of personal financial planning. Only CPAs who are members of the American Institute of Certified Public Accountants can earn this designation.

Certified Financial Planner (CFP): The CFP certification is one of the most recognized and prestigious credentials in the financial services industry. CFPs have completed a series of courses in investments, insurance, income taxes, estate, and retirement planning. They have also passed a comprehensive 10-hour certification exam. Additionally, CFPs must have at least 3 years of planning experience and meet stringent continuing education requirements as well as have a bachelorâ&#x20AC;&#x2122;s degree. While an estimated 700,000 people currently call themselves financial planners, only 1 in 10 holds the CFP designation. If you need help with more than 1 issue in your financial life or if you are targeting long-term goals like retirement or college, make sure a CFP is on your list.

Chartered Financial Consultant (ChFC): ChFCs have credentials similar to CFPs. ChFCs have completed a series of courses and exams

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covering financial, insurance, and estate planning subjects. The ChFC program provides financial planners and others in the financial services industry with in-depth knowledge of the skills needed to perform comprehensive financial planning for their clients.

Chartered Life Underwriter (CLU): CLUs are insurance agents who have completed comprehensive educational courses and demonstrated expertise in different areas of estate and insurance planning. This designation is specifically designed to enhance the knowledge of people employed in the life insurance industry.

CLUs must also have at least 3 years of professional experience.

Chartered Financial Analyst (CFA): CFAs have expertise in investing and portfolio management. They have passed 3 exams based on investment principles, applied financial analysis, and investment management. Each exam is approximately 6 hours in length. Additionally, CFAs must have at least 3 years of expe­ rience in the investment decision-making process. Generally, the CFA designation is recognized as the definitive standard for measuring competence and integrity in the fields of portfolio management and investment analysis.

The Steps Financial planning takes the guesswork out of managing your finances and helps you understand the implications of each financial decision you make. Everyone has different goals, so it is important to have a unique plan that works for you and your financial situation, both now and in the future. The following 7 steps will help you find an advisor who understands and meets your unique goals and needs.

Wealth Management

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Make a Well-Founded List of Prospective Advisors Begin your research by conducting an Internet search using the terms “physician financial advisor” or “physician financial planner.”

Look for signs of expertise such as published articles, a book, or maybe even a blog. A search outside of your community means you increase the odds of finding the best-qualified advice for the price you may pay. A search inside of your state means that the advisors you find are more likely to understand your financial environment, including your state’s tax laws, economy, job market, unique investment opportunities, and other factors that may impact the success of your financial plan. If you are concerned about the advisor’s location, keep in mind that today many financial advisors work with clients by telephone, e-mail, and video conference on a regular basis.

Next, it is important to search a few specific organizations. CFP Board (www.cfp.net) is a nonprofit organization acting in the public interest by fostering professional standards in personal financial planning through its setting and enforcement of the education, examination, experience, ethics, and other requirements for CFP certification.

The National Association of Personal Financial Advisors (www. napfa.org) is the country’s leading professional association of fee-only financial advisors. Finally, the Financial Planning Association (www. plannersearch.org) is the largest membership organization for CFP professionals in the United States and also includes members who support the financial planning process.

To round out your list of prospective advisors, ask your colleagues, your accountant, and your attorney who they recommend. Ask them why they believe this advisor is the best one for you. If their reason sounds valid, add the advisor to your list.

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Select for Quality Every prospective financial advisor on your list should have at least 1 real credential. Beware of generic pseudocredentials like financial advisor, financial consultant, and wealth manager. These titles merely signify that an advisor is in the business and may hold a license. Whereas most licenses require an advisor to pay a fee and pass an exam, these may be easily acquired with a minimal commitment of time and effort.

Conduct an Interview Every advisor on your newly trimmed list warrants a preliminary phone call. This is an interview, and you are the interviewer, not the interviewee, so make sure that you get the answers you need.

First and foremost, ask the candidate how he or she is paid. Planners can be paid in several ways: through fees, commissions, or a combination of both. Your financial planner should clearly state how he or she will be paid for the services to be provided.

Although there is no single method of paying for financial services that is inherently better than another, you will nevertheless want to consider, and discuss with your planner, how the method of compensation could affect the advice you receive or the way you work with the advisor. You and your financial planner should discuss these issues, including any conflicts of interest that may be created by the method of compensation.

Then ask whether the advisor has ever been publicly disciplined for any unlawful or unethical actions in his or her professional career. Several government and professional regulatory organizations, such as the Financial Industry Regulatory Authority, your state insurance and securities departments, and the CFP Board keep rec­ ords on the disciplinary history of financial planners and advisors. If a CFP professional violates any of the CFP Board’s standards, he is subject to disciplinary action up to permanent revocation of certification. Ask which organizations the planner is regulated by and contact these groups to conduct a background check. You can also visit http://brokercheck.finra.org.

Make appointments to visit advisors who remain on your list after this screening round.

Whereas most licenses require an advisor to pay a fee and pass an exam,...certifications usually require a higher level of commitment and dedication.

In contrast, certifications usually require a higher level of commitment and dedication. Formal training, rigorous examination, continuing education, years of experience, and oversight by a board or governing body are part of attaining and keeping a certificate, so certification is an outward indicator of the quality of advice you may receive. Narrow your list by crossing advisors off your list if they do not have at least 1 of the previously listed credentials.

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Do Your Homework Learn more about the advisors who remain on your list. Visit their websites, and search for answers to questions such as the following: • How long have you been in business?

• What type of clients do you work with?

• What services do you provide?

• What is your specialty?

• What is your approach to financial planning?

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Speak with at Least 3 Prospective Advisors Now you are ready to make the biggest mistake that most people Continued on page 33

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Clinical Trial Tracker

Trials Under Way for Patients with Melanoma

T

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

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

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Immunotherapy for Patients with Stage IV Melanoma This phase 2, randomized, open-label study aims to evaluate whether ipilimumab with or without HyperAcute-Melanoma immunotherapy can stop or slow the growth of tumors, or destroy tumors in patients with stage IV melanoma.

Patients aged ≥18 years may enroll if they have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1, and if they meet other enrollment criteria. Patients will receive a 3-mg/kg injection of ipilimumab every 3 weeks for 4 treatment cycles, with or without HyperAcute-Melanoma immunotherapy at 300 million cells per scheduled immunization.

Primary outcomes, measured over a time frame of 2 years, are the safety of administration of this combination therapy, and the clinical response rate of patients with metastatic melanoma after treatment. Secondary outcome measures include clinical activity, antitumor immune response, immune activation, and antitumor mechanism.

This study is expected to enroll 100 patients in Iowa City, IA; Winston-­ Salem, NC; and Knoxville, TN. For more information, contact Melanie Frees, RN, BSN, CCRC, at 319356-1228 or melanie-frees@uiowa. edu; Stacey Lewis, RN, at 336-7136927 or stalewis@wakehealth.edu; or Shanna Overbey at 865-3055281 or soverbey@utmck.edu, respectively. The NLM Identifier is NCT02054520.

2

Talimogene Laherparepvec plus Surgery versus Surgery Alone This phase 2, randomized, open-label study aims to estimate the efficacy of surgery after talimogene laherparepvec as a neoadjuvant treatment compared with surgery alone in patients with completely resectable stage IIIB, IIIC, or IVM1a melanoma. Patients aged ≥18 years with a histologically confirmed diagnosis of stage IIIB, IIIC, or IVM1a melanoma eligible for complete surgical resection may enroll if other criteria are met. Patients will either undergo immediate surgical resection of melanoma tumor lesions, or receive intralesional injections of talimogene laherparepvec followed by surgical resection of melanoma tumor lesions.

The primary outcome measure is the efficacy of neoadjuvant talimogene laherparepvec plus surgery versus surgery alone on recurrence-free survival at 24 months after the randomization of the last study patient.

Secondary outcome measures include efficacy at 3 and 5 years after the end of randomization, as well as overall response and safety. This study is expected to enroll 150 patients in Louisville, KY; Daytona Beach, FL; and Salt Lake City, UT. For more information, contact the Amgen Call Center at 866-5726436. The NLM Identifier is NCT02211131.

3

Dabrafenib plus Trametinib for Stage IV Melanoma This randomized, parallel­ assignment, open-label study aims to compare the safety and efficacy of receiving dabrafenib–trametinib combination therapy before surgery to surgery plus standard care in patients with clinical stage III or oligometastatic stage IV melanoma.

Patients aged ≥18 years with histologically or cytologically confirmed stage

IIIB/C or stage IV oligometastatic melanoma and an ECOG performance status of ≤1 may enroll if other criteria are met. Patients will receive surgery plus standard care, or dabrafenib–trametinib combination therapy plus surgery. Patients receiving the study drugs will continue to take them for ≤44 weeks after they recover from surgery.

The primary outcome measure is the relapse-free survival rate at 1 year, according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. This study is expected to enroll 84 patients at the University of Texas MD Anderson Cancer Center in Houston. For more information, contact Jennifer Wargo, MD, at 713-745-1553. The NLM Identifier is NCT02231775.

4

Dasatinib for Mucosal, Acral, or Vulvovaginal Melanomas This phase 2, open-label, multicenter study seeks to examine the effectiveness of dasatinib in treating patients with locally advanced or metastatic mucosal, acral, or vulvovaginal melanoma. Patients aged ≥18 years with acral melanoma (defined as melanoma occurring on the palms, soles, or subungual sites), melanoma occurring on the vulva/ vagina, or melanoma arising on other mucosal surfaces may be eligible to enroll if other criteria are met. Patients will receive oral dasatinib twice daily on days 1 to 21, and the course will be repeated every 21 days in the absence of unacceptable toxicity or disease progression.

The primary outcome measure is the objective tumor response rate.

Secondary outcome measures are response duration, progression-free survival, and the safety profile of the drug. This study is expected to enroll 87 patients at multiple locations across the United States. For more information, contact the Clinical Continued on page 32

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Oncology Practice Management

I May 2015

*The VELCADE Reimbursement Assistance Program does not file claims or appeal claims for callers, nor can it guarantee that you will be successful in obtaining reimbursement

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

Millennium Pharmaceuticals, Inc., Cambridge, MA 02139 Copyright Š 2010, Millennium Pharmaceuticals, Inc. All rights reserved.

Printed in USA

V-10-0196

11/10

Clinical Trial Tracker

Trials Under Way... Continued from page 30 Trials Office of Massachusetts General Hospital at 877-726-5130. The NLM Identifier is NCT00700882.

5

LGX818 plus MEK162 versus Vemurafenib and LGX818 Monotherapies This is a phase 3, randomized, open-label study comparing the efficacy and safety of LGX818– MEK162 combination therapy with vemurafenib and LGX818 monotherapies in patients with locally advanced, unresectable, or metastatic BRAF-mutated melanoma.

Patients aged ≥18 years with the presence of a BRAF V600E or V600K mutation in tumor tissue, an ECOG performance status of ≤1, and evidence of ≥1 measurable lesion (detected by radiologic or photographic methods) may enroll if other criteria are met.

In part 1 of the study, patients are randomized in a 1:1:1 ratio to 1 of 3 treatment arms: (1) 450 mg ­­of LGX818 once daily plus 45 mg of MEK162 twice daily; (2) 300 mg of LGX818 once daily; or (3) 960 mg of vemurafenib twice daily. In part 2, patients are randomized in a 3:1 ratio to 1 of 2 treatment arms: (1) 300 mg of LGX818 once daily plus 45 mg of MEK162 twice daily or (2) 300 mg of LGX818 once daily. The primary outcome measure is progression-free survival, defined as the time from the date of randomization to the first date of documented disease progression or death attributed to any cause. Secondary outcome measures include overall survival, safety and tolerability of combination therapy and LGX818 monotherapy, the pharmacokinetics of LGX818 and MEK162, and objective response rates.

This study is expected to enroll 900 patients at multiple locations throughout the United States and internationally. For more information, contact Novartis Pharmaceu-

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ticals at 888-669-6682. The NLM Identifier is NCT01909453.

6

Pembrolizumab plus Pegylated Interferon Alfa-2b or Ipilimumab This randomized, open-label, parallel-assignment study examines the safety, tolerability, and efficacy of combination regimens of pembroliz­umab plus pegylated interferon alfa-2b (PegIFN2b) and pembrolizu­mab plus ipilimumab for the treatment of advanced melanoma and renal-cell carcinoma.

Patients aged ≥18 years with an ECOG performance status of ≤1, adequate organ function, and no additional malignancies that are progressing or require active treatment (except for basal-cell carcinoma or squamous- cell carcinoma of the skin, or in situ cervical cancer that has experienced potentially curative therapy) may enroll if other criteria are met.

Patients will be randomized to receive pembrolizumab plus PegIFN2b, pembrolizumab plus ipilimumab, or pembrolizumab alone. Primary outcome measures are progression-free survival as well as the number of patients with dose-limiting toxicities, experiencing adverse events, and discontinuing the study drug because of adverse events. Secondary outcome measures include objective response rate and overall survival. This study is expected to enroll 343 patients at locations in California, Massachusetts, Texas, Washington, and Washington, DC. For more information, contact Merck at 888-577-8839. The NLM Identifier is NCT02089685.

7

High-Dose Interleukin-2 plus Ipilimumab This open-label, randomized, multicenter study compares the sequence of high-dose interleukin-2 and ipilimumab in patients with metastatic melanoma who are treatment-naïve or who have previously

Oncology Practice Management

I May 2015

received a single, nonimmunologic therapy. Patients aged ≥18 years with confirmed, measurable metastatic melanoma with ≥1 measurable lesion for evaluation of response, and who have not had adjuvant therapy or any other cancer treatments for ≥4 weeks may enroll if other criteria are met.

Patients will receive either 2 courses of high-dose interleukin-2 followed by 1 course of ipilimumab, or 1 course of ipilimumab followed by 2 courses of high-dose interleukin-2. The primary outcome measure is overall survival at 1 year.

This study is expected to enroll 100 patients at multiple locations across the United States. For more information, contact Theresa Luna at 858-882-8058 or tluna@prometheus labs.com. The NLM Identifier is NCT01856023.

8

Nivolumab Monotherapy versus Combination Therapy This phase 1, randomized, open-label study seeks to assess the biologic effects of nivolumab monotherapy versus nivolumab in combination with ipilimumab in patients with advanced unresectable or metastatic melanoma. Patients aged ≥16 years with unresectable stage III or IV melanoma who are refractory to, intolerant of, or have refused standard therapy, and who have an ECOG performance status of ≤1 may enroll if other criteria are met.

Patients will be separated into single-arm or parallel-group cohorts.

Primary outcomes are the immunomodulatory effects of nivolumab monotherapy and nivolumab– ipilimumab combination therapies, measured from day 1 through day 57. Secondary outcomes include safety and tolerability of nivolumab, ipilimumab, and nivolumab in combination with ipilimumab, as measured by laboratory test abnormalities, and the incidence of adverse

Clinical Trial Tracker

events, serious adverse events, death, and changes in vital signs. Objective response rates, durations of response, and progression-free survival will also be measured to determine antitumor activity. This study is expected to enroll 160 patients at multiple locations throughout the United States. For more information, contact Bristol-Myers Squibb at clinical.trials@bms.com. The NLM Identifier is NCT01621490.

9

Trametinib for Patients with Uveal Melanoma This phase 2, randomized, open-label study will examine the efficacy of trametinib with or without

GSK2141795 (a protein kinase B inhibitor) in treating patients with metastatic uveal melanoma. Patients aged ≥18 years with a life expectancy of >3 months, an ECOG performance status of ≤1, and no history of interstitial lung disease or pneumonitis may enroll if other criteria are met.

On days 1 to 28, patients in the first arm of the study will receive oral trametinib daily, and patients in the second arm will receive oral trametinib and oral GSK2141795 daily.

Courses are repeated every 4 weeks for both treatment arms in the absence of toxicity or disease progression. Patients in the first treatment arm who experience objective dis-

ease progression may cross over to the second treatment arm. The primary outcome is time to progression, measured from the date of randomization to death or the date of documented progression according to RECIST criteria. Secondary outcome measures include incidence of toxicity and response rate and overall survival per RECIST criteria.

This study is expected to enroll 80 patients at multiple locations throughout the United States and internationally. For more information, contact Paul B. Chapman, MD, at 646-888-4162 or chapmanp@ mskcc.org. The NLM Identifier is NCT01979523. l

Seven Steps to Finding... Continued from page 29 make when selecting an advisor: engaging the very first advisor you meet. While this may solve your immediate problem, it may lead to less-than-stellar results over the long haul. Why? Almost all advisors hold up well during the first interview. They have been interviewed hundreds of times and are ready to sign you up today. Resist the temptation to sign up for services at the first meeting. Instead, collect information and get a feel for how you and the advisor might work together over the longer haul.

6

Consider What You Have Learned Think about your interview with each advisor. Ask yourself these last few questions before making your final decision: • How well did each financial advisor listen to me? The hallmark of a good relationship with your financial advisor will be your ability to communicate your needs.

This means that he or she must do an excellent job of listening to you in order to understand how he or she can help.

ests, your outlook, and even some of the same financial goals you hold.

• How clearly did each financial advisor express himself or herself?

Even if you receive the very best financial advice from your new advisor, you might not follow the advice unless you fully understand it. Consider whether the advisor “speaks your language.”

• What promises did each financial advisor make? Consider how each advisor attempted to win you as a client. The best advisors attempt to set clear, realistic expectations about your work with them during the very first meeting. They know the foundation for a great, longterm advisor–client relationship is their ability to make promises and deliver on them.

Summary No matter which financial advisor you choose, make sure the one thing that you have in common is an uncompromised interest in your financial health. Start your search for a competent financial advisor today and begin enjoying better financial health tomorrow. l W. Ben Utley, CFP, is the lead advisor with Physician Family Financial Advisors, a fee-only financial planning firm helping doctors throughout the United States to save for college and invest for retirement. He can be reached at 541463-0899 or by e-mail to ben@physi cianfamily.com.

7

Select a Financial Advisor Who Suits You When you finally decide which advisor to hire, you may realize something that good financial advisors already know: the financial advisor you choose may be a lot like you. People have a natural tendency to trust others who are much like themselves, so the advisor you choose will likely share your inter-

May 2015

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 516-677-6211 or by e-mail to Lkeller@physicianfinancialservices. com with comments or questions.

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Drug Update

Akynzeo (Netupitant and Palonosetron), a Dual-Acting Oral Agent, Approved by the FDA for the Prevention of Chemotherapy-Induced Nausea and Vomiting

By Lisa A. Raedler, PhD, RPh, Medical Writer

O

ne of the most fear-inducing side effects of chemotherapy is nausea and vomiting.1 Without appropriate antiemetic prophylaxis, 70% to 80% of all patients with cancer who receive chemotherapy experience nausea and/or vomiting.2 Consequently, preventing and managing chemotherapy-induced nausea and vomiting (CINV) is a crucial part of care planning for patients with cancer.

In addition to being a distressing side effect of cancer treatment, CINV has multiple clinical consequences for patients, their families, and the healthcare system, including2-4: • Nonadherence to chemotherapy treatment • Early treatment discontinuation • Problems with appetite and eating, which can lead to nutritional deficits • Impaired daily functioning • Performance status decline3 • Impaired health-related quality of life, as assessed by the Functional Living Index–Emesis • More frequent office visits and emergency department admissions, and higher direct and indirect costs of care compared with patients without CINV. The economic costs associated with CINV are significant. In a study of working-aged adults who were receiving highly or moderately emetogenic chemotherapy, uncontrolled CINV was associated with higher costs; that is, the monthly medical

Copyright © 2015 American Health & Drug Benefits. Used with permission. All rights reserved.

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costs for patients with uncontrolled CINV were $1300 higher than the costs for patients without uncontrolled CINV. In addition, the monthly indirect costs, such as lost work time, were $400 higher for patients with uncontrolled CINV than for patients without uncontrolled CINV.4 Given the many potential negative effects of CINV, the use of effective antiemetic therapy is an essential part of treatment planning for patients undergoing chemotherapy and should be initiated at the start of cancer treatment.5 Several factors influence the incidence and severity of CINV. The primary risk factor for CINV is the chemotherapy regimen, including the type of chemotherapy agent, the route of administration, and the treatment dosage. Patient-related factors that influence CINV include sex and age. For example, women report CINV and other chemotherapy-associated adverse events more often than do men, and elderly patients report fewer side effects than younger patients.5 History of CINV, emesis during pregnancy, motion sickness, alcohol use, tumor burden, anxiety, concomitant medication and medical conditions, and inadequate hydration are also significant contributors to CINV.2 In practice, CINV is classified into 3 categories—acute onset occurs within 24 hours of the initial administration of chemotherapy; delayed onset occurs 24 hours to several days after the initial treatment; and anticipatory CINV is triggered by senses, thoughts, or anxiety that patients as-

Oncology Practice Management

I May 2015

sociate with previous chemotherapy.2 Current emesis-related management guidelines focus on the emetogenic potential of chemotherapy drugs and divide agents into 4 risk groups, including high, moderate, low, and minimal. Table 1 summarizes the classification of chemotherapy drugs according to the National Comprehensive Cancer Network (NCCN) guidelines, and provides examples of agents in each risk group.3 Supportive care for patients receiving chemotherapy has dramatically improved during the past 20 years, with combination antiemetic regimens emerging as the standard of care for CINV control.6 Four groups––the NCCN, the Multinational Association of Supportive Care in Cancer (MASCC), the European Society for Medical Oncology (ESMO), and the American Society of Clinical Oncology–– have published antiemetic guidelines.3,7,8 These groups broadly agree on the majority of key issues regarding the management of CINV.6 For acute emesis associated with highly emetogenic chemotherapy, as well as with the combination use of anthracycline and cyclophosphamide, antiemesis guidelines recommend triple therapy with a 5-­­­ hydroxytrypta­mine (5-HT3) receptor antagonist, dexamethasone, and a neurokinin 1 (NK1) receptor agonist.3,7,8 For acute emesis associated with moderately emetogenic regimens, the MASCC/ESMO guidelines recommend double therapy with a 5-HT3 receptor antagonist (ideally, palonosetron) and dexamethasone.

Drug Update

For low emetogenic chemotherapy, dexamethasone monotherapy is adequate, but for minimal emetogenic chemotherapy, prophylaxis for acute emesis is not recommended.6,7 For delayed emesis associated with highly emetogenic chemotherapy, the MASCC/ESMO guidelines recommend the combination of dexamethasone and an NK1 receptor agonist. For delayed emesis associated with moderately emetogenic chemotherapy, such as anthracycline and cyclophosphamide–based regimens, the guidelines recommend aprepitant monotherapy. In other moderately emetogenic regimens, dexamethasone or a 5-HT3 receptor antagonist (presuming the latter was not part of the primary prophylactic treatment) are the preferred agents.

For low- and minimal-emetogenic chemotherapy, no prophylaxis for delayed emesis is needed.6,7 Because maintaining dose inten­ sity of chemotherapy is important, particularly in early-stage disease, recommendations for highly emetogenic chemotherapy should be followed when nausea and vomiting are not reduced by the recommended therapy for moderately emetogenic chemotherapy.5 Although the majority of patients with cancer are protected from CINV with these current therapies, other patients still experience nausea and vomiting associated with chemotherapy. Consequently, there remains a need for greater adherence to treatment guidelines and for more effective antiemetic agents.2,5

FDA Approves a Novel Combination Therapy for CINV On October 10, 2014, the US Food and Drug Administration (FDA) approved the combination of netupitant plus palonosetron (Akynzeo; Eisai) for the prevention of acute and delayed nausea and vomiting associated with initial and

Table 1 Classification of Emetogenic Risk Associated with Some Chemotherapy Agents Proportion of patients experiencing acute emesis without Emetogenic risk prophylaxis, % Examples of IV chemotherapies High

Cisplatin, high-dose cyclophosphamide, dacarbazine

≥90

Moderate

30-90

Carboplatin, high-dose cytarabine, doxorubicin, irinotecan, oxaliplatin

Low

10-30

Cabazitaxel, docetaxel, floxuridine, gemcitabine, pemetrexed, temsirolimus, topotecan

Minimal

Bevacizumab, fludarabine, vincristine, vinorelbine

<10

IV indicates intravenous.

Source: National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): antiemesis. Version 2.2014. April 18, 2014.

a 5-HT3 antagonist. Acute emesis is known to depend on serotonin and its 5-HT3 receptors.10 Netupitant is a selective antagonist of human substance P and NK1 receptors. These receptors are broadly distributed in the central and the peripheral nervous systems. Delayed emesis is associated with the activation of NK1 receptors by substance P. In vitro and in vivo studies demonstrated that netupitant inhibits substance P–mediated responses.10

repeated courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy in patients with cancer.9,10 The fixed combination capsule of netupitant plus palonosetron contains 300 mg of netupitant and 0.5 mg of palonosetron.10 Oral palonosetron was initially approved as a single agent in 2008 for the prevention of acute nausea and vomiting associated with initial and repeated courses of moderately emetogenic chemotherapy in patients with cancer.9,11 Palonosetron prevents nausea and vomiting during the acute phase. Netupitant is a new drug that prevents nausea and vomiting during the acute and the delayed phases after the start of chemotherapy.9,10 “Supportive care products, such as Akynzeo, help ease the nausea and vomiting patients may experience as a side effect of cancer chemotherapy,” said Julie Beitz, MD, Director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.9

Dosing and Administration Netupitant plus palonosetron is a fixed-dose combination capsule containing netupitant (300 mg) and palonosetron (0.5 mg).10 For patients undergoing highly emetogenic chemotherapy, including cisplatin-based chemotherapy, the recommended dosage of netupitant plus palonosetron is 1 capsule given approximately 1 hour before starting chemotherapy, with oral dexamethasone 12 mg administered 30 minutes before the start of chemotherapy on day 1 and dexamethasone 8 mg once daily on days 2 to 4.10 For patients receiving anthracycline and cyclophosphamide or other chemotherapy that is not considered

Mechanism of Action Palonosetron has a strong binding affinity for 5-HT3 receptors, acting as

Continued on page 40

May 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

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 7.4

6.6

4.5

3.8

6.6

0.0

4.5

0.0

4.3

0.3

1.8

0.0

4.0

0.3

1.8

0.0

0.0

6.5

0.3

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

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 g Infection 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

Akynzeo (Netupitant and Palonosetron)... Continued from page 35 tudy 1: Netupitant plus Palonosetron versus Palonosetron Alone Table 2 S in Patients Receiving Highly Emetogenic Chemotherapy Complete response rate Phase after cisplatin chemotherapy Acute phasea b

Delayed phase c

Overall

Netupitant 300 mg + palonosetron 0.5 mg, % (N = 135)

Palonosetron 0.5 mg, % (N = 136)

P value

98.5

89.7

.002

90.4

80.1

.032

89.6

76.5

.003

0-24 hours after treatment.

25-120 hours after treatment. c 0-120 hours after treatment.

Source: Akynzeo (netupitant and palonosetron) capsules prescribing information; October 2014. a

b

highly emetogenic, the recommended dosage of the new combination is 1 capsule approximately 1 hour before the start of chemotherapy, with dexamethasone 12 mg administered 30 minutes before the start of chemotherapy on day 1. The subsequent administration of dexamethasone is not necessary.10 Netupitant plus palonosetron can be taken with or without food.10

Clinical Trials The efficacy and safety of fixeddose netupitant plus palonosetron in combination with dexamethasone were evaluated in 2 randomized, parallel, double-blind, multicenter, controlled clinical trials––1 clinical trial in patients receiving highly emetogenic chemotherapy and 1 clinical trial in patients receiving moderately emetogenic chemotherapy.10 Study 1: Highly Emetogenic Chemotherapy This multicenter, randomized, parallel, double-blind study enrolled 694 chemotherapy-naïve patients with cancer who were receiving cisplatin-based chemotherapy (median dose, 75 mg/m2).10,12 This trial evaluated 3 oral doses of netupitant (100 mg, 200 mg, and 300 mg) combined

with oral palonosetron 0.5 mg and compared it with oral palonosetron 0.5 mg alone, all administered on day 1.10,12 A standard 3-day aprepitant and intravenous ondansetron regimen were included as an exploratory arm. All patients received oral dexamethasone on days 1 through 4.12 Of the 694 patients who enrolled in this clinical trial, 135 patients received netupitant plus palonosetron (netupitant 300 mg and palonosetron 0.5 mg), and 136 patients received oral palonosetron 0.5 mg alone.10 The majority of patients who received netupitant plus palonosetron were male (57%) and white (100%); the patients’ median age was 53 years (range, 19-77 years).10 During the study, 86% of patients who received netupitant plus palonosetron also received a concomitant chemotherapeutic agent in addition to cisplatin, including cyclophosphamide (34%), fluorouracil (24%), etoposide (21%), and doxorubicin (16%).10 The key efficacy end points were the complete response rates (defined as no emetic episode and no use of rescue medication) 0 to 24 hours after cisplatin treatment (acute phase), 25 to 120 hours after cisplatin treatment (delayed phase), and

within 120 hours after cisplatin treatment (overall phase).10,12 Table 2 summarizes the efficacy data for netupitant plus palonosetron versus palonosetron alone, which show that the netupitant plus palonosetron combination offers clinically significant improvements in the complete response rates over palonosetron alone.10,12 Study 2: Moderately Emetogenic Chemotherapy In this multicenter, randomized, parallel, double-­blind, active-control superiority study, the efficacy and safety of a single oral dose of netupitant plus palonosetron were compared with a single oral dose of palonosetron 0.5 mg in 1450 chemotherapy-naïve patients with cancer who were scheduled to receive an­ thracycline and cyclophosphamide.10,13 Patients in this clinical trial also received a single oral dose of dexamethasone. After completing their first cycle of anthracycline and cyclophosphamide, patients could participate in a multiple-cycle extension in which they continued the same antiemetic treatment as assigned in cycle 1.10 A total of 725 patients received netupitant plus palonosetron, and 725 patients received palonosetron alone.10,13 Overall, 1438 patients completed cycle 1 of chemotherapy, and the majority (88%) of patients continued treatment in the multiple-cycle extension. A total of 907 (62%) patients finished the multiple-cycle extension for a maximum of 8 treatment cycles.10 The majority of patients who received the netupitant plus palonosetron combination were female (98%) and white (79%); the patients’ median age was 54 years (range, 22-79 years).10 Overall, nearly all patients (99.9%) received cyclophosphamide and an anthracycline; in addition, all Continued on page 42

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Oncology Practice Management

I May 2015

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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Drug Update

Akynzeo (Netupitant and Palonosetron)... Continued from page 40 patients received either doxorubicin (68%) or epirubicin (32%).10 During the first cycle of chemotherapy, 32% of patients who received netupitant plus palonosetron also received a concomitant chemotherapeutic agent in addition to the protocol-mandated regimens, including fluorouracil (28%) and docetaxel (3%).10 The efficacy end points included the complete response rates for the acute phase, the delayed phase, and the overall phase after chemotherapy with an anthracycline plus cyclophosphamide.10,13 Table 3 summarizes the efficacy data for netupitant plus palonosetron versus palonosetron monotherapy, which show that the combination of netupitant plus palonosetron offers significant improvements in complete response rate over palonosetron monotherapy.10,13 Among the patients who participated in the multiple-cycle extension of the study, the antiemetic activity of netupitant plus palonosetron was maintained throughout the repeated cycles of chemotherapy.10

Adverse Reactions The safety of netupitant plus palonosetron was evaluated in clinical trials that included more than 1500 healthy volunteers and patients with cancer.10 More than 1150 patients with cancer have been exposed to netupitant plus palonosetron, receiving at least 1 cycle of cancer chemotherapy in 1 of 3 active-controlled clinical trials, including 782 patients who were exposed to netupitant plus palonosetron for at least 4 cycles, and 321 patients who were exposed to netupitant plus palonosetron for at least 6 cycles, up to a maximum of 12 cycles of chemotherapy.10 All patients received a single oral dose of netupitant plus palonosetron 1 hour before the start of each chemotherapy cycle. In all the studies,

42

I

tudy 2: Netupitant plus Palonosetron versus Palonosetron Alone Table 3 S in Patients Receiving Moderately Emetogenic Chemotherapy Complete response rate Status after anthracycline/ Netupitant 300 mg + cyclophosphamide palonosetron 0.5 mg, % chemotherapy (N = 724) Acute phasea b

Delayed phase c

Overall

Palonosetron 0.5 mg, % (N = 725)

P value

88.4

85.0

.047

76.9

69.5

.001

74.3

66.6

.001

0-24 hours after treatment.

25-120 hours after treatment. c 0-120 hours after treatment.

Source: Akynzeo (netupitant and palonosetron) capsules prescribing information; October 2014. a

b

dexamethasone was coadministered with netupitant plus palonosetron.10 Cisplatin-Based Highly Emetogenic Chemotherapy In a single-cycle study of patients who received cisplatin-based highly emetogenic chemotherapy, 136 patients received netupitant plus palonosetron.10 Adverse reactions that were reported at an incidence rate of at least 3% and for which the rate with netupitant plus palonosetron exceeded the rate with palonosetron alone included dyspepsia (4%), fatigue (4%), constipation (3%), ­­and erythema (3%).10 Anthracycline and Cyclophosphamide–Based Moderately Emetogenic Chemotherapy In a study of patients who received moderately emetogenic chemotherapy, 725 patients received netupitant plus palonosetron during the first cycle, and 635 of these patients continued for up to 8 cycles in a multiple-cycle extension.10 The adverse reactions that were reported at an incidence rate of at least 3% and for which the rate with netupitant plus palonosetron exceeded the rate with palonosetron alone during cycle 1

Oncology Practice Management

I May 2015

included headache (9%), asthenia (8%), and fatigue (7%).10 The adverse reactions associated with netupitant plus palonosetron during subsequent cycles of anthracycline and cyclophosphamide were similar to those observed in the first cycle.10 In both treatment arms of the clinical trials that compared netupitant plus palonosetron with oral palonosetron monotherapy, concomitant elevations of total bilirubin and transaminase levels of more than 3 times the upper limit of normal were reported, and the frequency of these elevations was similar with both treatments.10 The combination of netupitant plus palonosetron has no contra­ indications.10

Drug Interactions Netupitant plus palonosetron should be used with caution in patients receiving cytochrome (CY) P3A4 substrates (eg, tacrolimus, imatinib, anastrozole, paclitaxel); inhibition of CYP3A4 can result in increased plasma concentrations of the concomitant drug that can last for 4 days or more. The concomitant use of netupitant plus palonosetron with CYP3A4 inducers (eg, rifam­ pin, carbamazepine, phenobarbital, pioglitazone) should be avoided.10,14

Drug Update

Warnings and Precautions Hypersensitivity. Hypersensitivity reactions, including anaphylaxis, have been reported after the use of other 5-HT3 receptor antagonists.10 Patients experiencing anaphylaxis may or may not have a known hypersensitivity to 5-HT3 receptor antagonists. Patients taking netupitant plus palonosetron should seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur.10 Serotonin syndrome. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, most often when serotonergic drugs (eg, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol) were used concomitantly; several of the cases were fatal.10 The symptoms associated with serotonin syndrome can include mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia); neuromus­ cular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination); and seizures, with or without gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If symptoms of serotonin syndrome occur, netupitant/palonosetron should be discontinued and supportive treatment should be initiated.10 Use in Specific Populations Pregnancy. Netupitant plus palonosetron is listed ­­as pregnancy category C; there are no adequate and well-controlled studies with this combination in pregnant women.

Netupitant plus palonosetron should only be used during pregnancy if the potential benefit outweighs the potential risk to the fetus.10

Nursing mothers. It is not known whether the components of netupitant plus palonosetron are present in human breast milk. Nursing or netupitant plus palonosetron therapy should be discontinued on the basis of the importance of the drug to the mother.10 Pediatric use. The safety and efficacy of netupitant plus palonosetron have not been established in pediatric patients aged <18 years.10 Geriatric use. Of the 1169 patients with cancer who received netupitant plus palonosetron in clinical trials, 18% were aged ≥65 years, and 2% were aged ≥75 years.10 The nature and the frequency of adverse events were similar between elderly patients and younger patients. In general, caution should be used when administering netupitant plus palonosetron to elderly patients, because of their higher risk for hepatic, renal, and/or cardiac dysfunction, as well as concomitant diseases and multiple medications.10 Renal impairment. Patients with mild or moderate renal impairment do not require dose adjustment of netupitant plus palonosetron.10 Patients with severe renal impairment or end-stage renal disease should not receive netupitant plus palonosetron.10 Hepatic impairment. No dosage adjustment of netupitant plus palonosetron is recommended for patients with mild or with moderate hepatic impairment. Netupitant plus palonosetron is not recommended for use in patients with severe hepatic impairment.10

This novel dual-acting prophylactic therapy is an important option for patients receiving chemotherapy, in part because adherence to antiemetic consensus guidelines remains low. As an oral single capsule, the use of netupitant plus palonosetron combination therapy may improve the management of patients with cancer who are at high risk for CINV. l

References

1. Sun CC, Bodurka DC, Weaver CB, et al. Rankings and symptom assessments of side effects from chemotherapy: insights from experienced patients with ovarian cancer. Support Care Cancer. 2005;13:219-227.

2. Feyer P, Jordan K. Update and new trends in antiemetic therapy: the continuing need for novel therapies. Ann Oncol. 2011;22:30-38.

3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): antiemesis. Version 2.2014. April 18, 2014. www.nccn.org/professionals/physician_gls/pdf/antiemesis. pdf. Accessed February 23, 2015.

4. Tina Shih Y-C, Xu Y, Elting LS. Costs of uncontrolled chemotherapy-­ induced nausea and vomiting among working-age cancer patients receiving highly or moderately emetogenic chemotherapy. Cancer. 2007; 110:678-685.

5. Morrow GR, Navari RM, Rugo HS. Clinical roundtable monograph: new data in emerging treatment options for chemotherapy-induced nausea and vomiting. Clin Adv Hematol Oncol. 2014;12(3 suppl 9):1-14; quiz 15.

6. Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008;358:2482-2494.

7. Roila F, Herrstedt J, Aapro M, et al; for the ESMO/ MASCC Guidelines Working Group. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference.

Ann Oncol. 2010;21(suppl 5):v232-v243.

8. Basch E, Prestrud AA, Hesketh PJ, et al; for the American Society of Clinical Oncology. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011;29:4189-4198.

Erratum in: J Clin Oncol. 2014;32:2117.

9. US Food and Drug Administration. FDA approves Akynzeo for nausea and vomiting associated with cancer chemotherapy. Press release. October 10, 2014. www. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm418375.­htm. Accessed February 20, 2015.

10. Akynzeo (netupitant and palonosetron) capsules [prescribing information]. Woodcliff Lake, NJ: Eisai Inc; October 2014.

11. Aloxi (palonosetron HCl) capsules [prescribing information]. Woodcliff Lake, NJ: Eisai Inc; September 2014.

12. Hesketh PJ, Rossi G, Rizzi G, et al. Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-­induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study. Ann Oncol. 2014;25:1340-1346.

13. Aapro M, Rugo H, Rossi G, et al. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol. 2014;25:1328-1333.

14. Stenger M. Fixed-combination netupitant/palonosetron for prevention of chemotherapy-induced nausea and vomiting. ASCO Post. 2014;5:119.

Conclusion The new fixed-dose combination agent that targets 2 antiemetic pathways, netupitant plus palonosetron offers an effective and safe alternative for patients undergoing initial and repeated courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

May 2015

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www.OncPracticeManagement.com

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

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

Navigation-related research and outcomes (poster presentations and educational sessions) Tumor-specific and skills breakout sessions Continuing education units Celebratory events for survivors, caregivers, navigators and their healthcare team members Network and create relationships with peers and key thought leaders

WHO SHOULD ATTEND: Oncology nurse navigators

Administrators

Practice managers

Patient or non-clinically licensed oncology navigators

Case managers

Financial counselors

Oncology nurses and nurse practitioners

Oncologists

Oncology social workers

TRAVEL GRANT OPPORTUNITIES: Navigators who meet certain criteria can apply for a travel grant that will allow them to participate in AONN+ educational and networking events. Learn more or apply at AONNonline.org/travel-grant/

CONFERENCE CO- CHAIRS Lillie Shockney, RN, BS, MAS University Distinguished Service Associate Professor of Breast Cancer Administrative Director, The Johns Hopkins Breast Center

AONN+ is pleased to present two new initiatives this year!

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

A special one-day

Associate Professor, JHU School of Nursing, Baltimore, Maryland

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

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

PATIENT NAVIGATION TRACK specifically geared toward patient and non-clinically licensed oncology navigators (Saturday, October 3) Specific

MULTI-STAKEHOLDER SESSIONS in partnership with the Association for Oncology Practice Management (AOPM) focused on the team approach with oncologists and financial counselors

AWARDS AND RECOGNITION: The Hero of Hope Awardâ&#x201E;˘ honors a person with cancer who has demonstrated great strength, spirit, grace and compassion during their battle.

Learn more or nominate your hero at AONNonline.org/community/heroes-of-hope/

The Oncology Nurse Excellence (ONE) Award recognizes an oncology nurse for outstanding contribution to oncology nursing practice, patient care and education.

Learn more or submit a nomination at TheOncologyNurse.com/one-award

FEES: AONN+ Member:

Non-AONN+ Member:

Patient Navigator Track only

Patient Navigator Track only

$75 (early bird fee*)/$100 standard fee

$90 (early bird fee*)/$115 standard fee

Full Conference plus Patient Navigator Track

Full Conference plus Patient Navigator Track

$300 (early bird fee*)/$350 standard fee

$425 (early bird fee*)/$475 standard fee *early bird rates end 5/31/15

Visit AONNonline.org to view the complete agenda and register today!

AnnualConference_RegisterToday_Asize_spread031215

Drug Coding Supplied by RJ Health Systems

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

The following sections include: • Associated ICD-9-CM codes used for the classification of leukemia • Drugs that have been FDA approved in the treatment of leukemia • Drugs that are Compendia-listed for off-label use for leukemia based on clinical studies that suggest beneficial use in some cases. Please note: If a check mark appears in the FDA column, it will NOT appear in the Compendia off-label use column • Corresponding HCPCS/CPT® codes and code descriptions • Drugs listed in the Compendia section have no FDA-approved uses for leukemia. However, drugs in the FDA-approved section are FDA approved for at least 1 of the leukemia ICD-9-CM codes but may also have Compendia-listed uses as well

Associated ICD-9-CM codes for the treatment of leukemia: lymphogenous 204.0 Acute Excludes: acute exacerbation of chronic lymphoid leukemia (204.1) 204.1 Chronic 204.2 Subacute 204.8 Other lymphoid leukemia

Aleukemic leukemia:

lymphatic lymphocytic lymphoid 204.9 Unspecified lymphoid leukemia

202 Other malignant neoplasms of lymphoid and histiocytic tissue The following fifth-digit subclassification is for use with category 202:

0 unspecified site, extranodal and solid organ sites

1 lymph nodes of head, face, and neck

2 intrathoracic lymph nodes

3 intra-abdominal lymph nodes

4 lymph nodes of axilla and upper limb

5 lymph nodes of inguinal region and lower limb

6 intrapelvic lymph nodes 7 spleen

8 lymph nodes of multiple sites 202.4 Leukemic reticuloendotheliosis

Hairy-cell leukemia 204-208 Leukemia The following fifth-digit subclassification is for use with categories 204-208: 0 without mention of having achieved remission >Failed remission<

1 in remission

2 in relapse 204 Lymphoid leukemia

Includes: leukemia:

lymphatic lymphoblastic lymphocytic

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205 Myeloid leukemia

Includes: leukemia: granulocytic myeloblastic

myleocytic myelogenous myelomonocytic myelosclerotic myelosis 205.0 Acute

Acute promyelocytic leukemia

Excludes: acute exacerbation of chronic myeloid leukemia (205.1) 205.1 Chronic

Eosinophilic leukemia Neutrophilic leukemia 205.2 Subacute

Drug Coding

205.3 Myeloid sarcoma

Chloroma Granulocytic sarcoma 205.8 Other myeloid leukemia

Aleukemic leukemia: granulocytic myelogenous myeloid Aleukemic myelosis 205.9 Unspecified myeloid leukemia 206 Monocytic leukemia

Includes: leukemia: histiocytic monoblastic monocytoid 206.0 Acute

Excludes: acute exacerbation of chronic monocytic leukemia (206.1) 206.1 Chronic 206.2 Subacute 206.8 Other monocytic leukemia

Aleukemic: monocytic leukemia monocytoid leukemia 206.9 Unspecified monocytic leukemia

207 Other specified leukemia

Excludes: leukemic reticuloendotheliosis (202.4)

plasma cell leukemia (203.1) 207.0 Acute erythremia and erythroleukemia

Acute erythremic myelosis Di Guglielmo’s disease Erythremic myelosis 207.1 Chronic erythremia

Heilmeyer-Schöner disease 207.2 Megakaryocytic leukemia

Megakaryocytic myelosis Thrombocytic leukemia 207.8 Other specified leukemia

Lymphosarcoma cell leukemia 208 Leukemia of unspecified cell type 208.0 Acute

Acute leukemia not otherwise specified Stem cell leukemia Blast cell leukemia

Excludes: acute exacerbation of chronic unspecified leukemia (208.1) 208.1 Chronic

Chronic leukemia not otherwise specified 208.2 Subacute

Subacute leukemia not otherwise specified 208.8 Other leukemia of unspecified cell type 208.9 Unspecified leukemia Leukemia not otherwise specified FDA approved for leukemia

Compendia off-label use for leukemia

Possible CPT ® administration codes

Generic (brand) name

HCPCS code - code description

aldesleukin (Proleukin)

J9015 - Injection, aldesleukin, per singleuse vial

√

96409

amifostine (Ethyol)

J0207 - Injection, amifostine, 500 mg

√

96374

arsenic trioxide (Trisenox)

J9017 - Injection, arsenic trioxide, 1 mg

√

96413, 96415

asparaginase Erwinia chrysanthemi (Erwinaze)

J9019 - Injection, asparaginase (Erwinaze), 1000 IU

√

96401

azacitidine (Vidaza)

J9025 - Injection, azacitidine, 1 mg

√

96401, 96409, 96413

Bacillus Calmette-Guérin (BCG Vaccine)

90585 - Bacillus Calmette-Guérin vaccine (BCG) for tuberculosis, live, for percutaneous

√

90471, 90472

Bacillus Calmette-Guérin (Tice BCG, TheraCys)

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

√

51720

Bacillus Calmette-Guérin (Tice BCG, TheraCys)

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

√

51720

bendamustine (Treanda)

J9033 - Injection, bendamustine hydrochloride, 1 mg

96413

√

Continued on page 48

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Drug Coding

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betamethasone acetate & sodium phosphate (Celestone Soluspan)

J0702 - Injection, betamethasone acetate, 3 mg, and betamethasone sodium phosphate, 3 mg

√

11900, 11901, 20600, 20605, 20610, 96372

blinatumomab (Blincyto)

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

√

96413, 96415

blinatumomab (Blincyto)

*J9999 - Not otherwise classified, antineoplastic drugs

√

96413, 96415

bosutinib (Bosulif)

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

√

N/A

bosutinib (Bosulif)

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

√

N/A

busulfan (Busulfex)

J0594 - Injection, busulfan, 1 mg

√

96415, 96416

busulfan (Myleran)

J8510 - Busulfan, oral, 2 mg

√

N/A

carboplatin (Paraplatin)

J9045 - Injection, carboplatin, 50 mg

chlorambucil (Leukeran)

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

√

N/A

chlorambucil (Leukeran)

S0172 - Chlorambucil, oral, 2 mg

√

N/A

cladribine (Leustatin)

J9065 - Injection, cladribine, per 1 mg

√

96413, 96415

clofarabine (Clolar)

J9027 - Injection, clofarabine, 1 mg

√

96413, 96415

cyclophosphamide (Cytoxan)

J9070 - Cyclophosphamide, 100 mg

√

96409, 96413, 96415

cyclophosphamide (Cytoxan)

J8530 - Cyclophosphamide, oral, 25 mg

√

N/A

cytarabine (Cytosar-U)

J9100 - Injection, cytarabine, 100 mg

√

96409, 96413, 96415, 96450

dasatinib (Sprycel)

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

√

N/A

daunorubicin (Cerubidine)

J9150 - Injection, daunorubicin, 10 mg

√

daunorubicin citrate liposome (DaunoXome)

J9151 - Injection, daunorubicin citrate, liposomal formulation, 10 mg

√

96413

decitabine (Dacogen)

J0894 - Injection, decitabine, 1 mg

√

96413, 96415

dexamethasone (Decadron)

J8540 - Dexamethasone, oral, 0.25 mg

√

N/A

dexamethasone (eg, Decadron)

J1100 - Injection, dexamethasone sodium phosphate, 1 mg

√

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

doxorubicin (Adriamycin)

J9000 - Injection, doxorubicin hydrochloride, 10 mg

√

96409

epirubicin (Ellence)

J9178 - Injection, epirubicin hydrochloride, 2 mg

√

96409, 96413

etoposide (VePesid)

J8560 - Etoposide, oral, 50 mg

√

N/A

etoposide (Toposar)

J9181 - Injection, etoposide, 10 mg

√

96413, 96415

filgrastim (Neupogen)

J1442 - Injection, filgrastim (G-CSF), 1 microgram

√

96365, 96366, 96369, 96370, 96372, 96374

Oncology Practice Management

I May 2015

√

96409, 96413, 96415

96409, 96413

Drug Coding

fludarabine (Fludara)

J9185 - Injection, fludarabine phosphate, 50 mg

√

96413

hydrocortisone (Solu-Cortef)

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

√

96365, 96366, 96372, 96374

hydroxyurea (Hydrea)

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

√

N/A

hydroxyurea (Hydrea)

S0176 - Hydroxyurea, oral, 500 mg

√

N/A

ibrutinib (Imbruvica)

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

√

N/A

idarubicin (Idamycin)

J9211 - Injection, idarubicin hydrochloride, 5 mg

√

96409

ifosfamide (Ifex)

J9208 - Injection, ifosfamide, 1 gram

imatinib (Gleevec)

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

√

imatinib (Gleevec)

S0088 - Imatinib,100 mg

√

interferon alfa-2b (Intron A)

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

√

96372, 96401

irinotecan (Camptosar)

J9206 - Injection, irinotecan, 20 mg

√

96413, 96415

mechlorethamine (Mustargen)

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

melphalan (Alkeran)

J8600 - Melphalan, oral, 2 mg

√

N/A

melphalan (Alkeran)

J9245 - Injection, melphalan hydrochloride, 50 mg

√

96409, 96413

mercaptopurine (Purinethol)

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

√

N/A

mercaptopurine (Purinethol)

S0108 - Mercaptopurine, oral, 50 mg

√

N/A

methotrexate

J8610 - Methotrexate, oral, 2.5 mg

√

N/A

methotrexate

J9250 - Methotrexate sodium, 5 mg

√

96372, 96374, 96401, 96409, 96450

methotrexate

J9260 - Methotrexate sodium, 50 mg

√

96372, 96374, 96401, 96409, 96450

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 (Medrol)

J7509 - Methylprednisolone, oral, per 4 mg

√

N/A

mitoxantrone (Novantrone)

J9293 - Injection, mitoxantrone hydrochloride, per 5 mg

√

96409, 96413

nelarabine (Arranon)

J9261 - Injection, nelarabine, 50 mg

√

96413, 96415

√

96413, 96415 N/A N/A

96409

√

Continued on page 50

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Drug Coding

nilotinib (Tasigna)

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

√

N/A

obinutuzumab (Gazyva)

J9301 - Injection, obinutuzumab, 10 mg

√

96413, 96415

ofatumumab (Arzerra)

J9302 - Injection, ofatumumab, 10 mg

√

96413, 96415

omacetaxine mepesuccinate (Synribo)

J9262 - Injection, omacetaxine mepesuccinate, 0.01 mg

√

96401

pegaspargase (Oncaspar)

J9266 - Injection, pegaspargase, per single-dose vial

√

96401, 96413, 96415

pentostatin (Nipent)

J9268 - Injection, pentostatin, per 10 mg

√

96409, 96413

ponatinib (Iclusig)

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

√

N/A

ponatinib (Iclusig)

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

√

N/A

prednisolone (Millipred)

J7510 - Prednisolone, oral, per 5 mg

√

N/A

prednisone (Deltasone)

J7506 - Prednisone, oral, per 5 mg

√

N/A

rituximab (Rituxan)

J9310 - Injection, rituximab, 100 mg

√

96413, 96415

sodium phosphate P 32

A9563 - Sodium phosphate P 32, therapeutic, per millicurie

√

79101

temozolomide (Temodar)

J8700 - Temozolomide, oral, 5 mg

teniposide (Vumon)

Q2017 - Injection, teniposide, 50 mg

topotecan (Hycamtin)

J9351 - Injection, topotecan, 0.1 mg

vinCRIStine (Vincasar PFS)

J9370 - Vincristine sulfate, 1 mg

√

96409

vinCRIStine liposome (Marqibo)

J9371 - Injection, vincristine sulfate liposome, 1 mg

√

96413

zidovudine (Retrovir)

*J8499 - Prescription drug, oral, nonchemotherapeutic; not otherwise specified

√

N/A

zidovudine (Retrovir)

S0104 - Zidovudine, oral, 100 mg

√

N/A

√

N/A 96413, 96415

√ √

96413

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

References • HCPCS Level II Expert 2015 • Current Procedural Terminology (CPT ®) 2015 • CPT copyright 2015 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association • ICD-9-CM for Professionals Volumes 1 & 2, 2015 • FDA-approved indication (product Prescribing Information) • Compendia references available upon request • www.ReimbursementCodes.com powered by RJ Health Systems International, LLC, Rocky Hill, CT • CMS (Centers for Medicare & Medicaid Services) GM-CSF indicates granulocyte-macrophage colony-stimulating factor; HCPCS, Healthcare Common Procedure Coding System.

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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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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