OPM June 2014

JUNE 2014

www.OncPracticeManagement.com

VOLUME 4 • NUMBER 4

Oncology Practice Management ™

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

Providing Social Support to Patients with Cancer Interview with Vicki Kennedy, LCSW, Vice President of Program Development and Delivery Cancer Support Community, Washington, DC

The following interview was conducted recently with Vicki Kennedy, LCSW, at the 2014 conference of the Association for Value-Based Cancer Care.

Q: What do you feel is the most press-­ ing need a­mong patients with cancer and their caregivers?

Ms Kennedy: Today, when we think about cancer and its effect on the whole person’s life, it really is… having the cancer healthcare team understand all of the dimensions Continued on page 15

ICD-9 or ICD-10: What Is the Point?

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

R

egardless of which version you are considering, the International Classification of Diseases, Clinical Modification (ICD-CM) is a morbidity classification published by the United States for classifying diagnoses and rea­ sons for visits in all healthcare settings.

ICD-CM is based on ICD, the statisti­

cal classification of diseases published by the World Health Organization.

Unfortunately, to most providers and coders in the United States, the ICDCM code set has been reduced simply to a means of reimbursement. That narrow thinking may completely miss the point.

Continued on page 6

Shopping for High-Quality, Affordable Oncology Care

By Carla Balch, CEO, Altos Solutions, a Division of Flatiron Health, Inc, New York City

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y grandmother always told me, “Buy the best you can afford.” Contained in this sim­ ple advice, something we all have likely heard in one form or another, are a couple of key concepts worth extracting as they pertain to the oncology industry: the words “buy” and “best.”

The first word, “buy,” infers that a dec­

ision has been made to purchase some­ thing, likely after shopping. But how does one shop for healthcare, for an oncologist, or for an oncology practice?

Various websites (eg, healthgrades.com, Medicare’s Physician Compare, and payers’ Find a Provider option) provide some guidance, but they do not provide Continued on page 8

From the publishers of

INTEGRATING ONCOLOGISTS, PAYERS, AND THE ENTIRE CANCER CARE TEAM

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ew or : N er f 7 g E in g …

TH und hanices M po e C act O m m Pr FR Co Ga gy o g ru a ol D ule nc R O

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© 2014 Engage Healthcare Communications, LLC

We Will

exhaust all possibilities.

We will…because patients are our priority.

Celgene Patient Support ® provides free and personalized assistance with patients’ access and reimbursement needs.

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Celgene Patient Support® is a registered trademark of Celgene Corporation. © 2013 Celgene Corporation 09/13 US-CELG110059(1)

Head June 2014 • Volume 4 • Number 4

Table of Contents PUBLISHING STAFF Senior Vice President/Group Publisher Nicholas Englezos nenglezos@the-lynx-group.com Vice President/Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Publisher Cristopher Pires cpires@the-lynx-group.com Director, Client Services Lou Lesperance llesperance@the-lynx-group.com Editorial Directors Dalia Buffery dbuffery@the-lynx-group.com Anne Cooper acooper@the-lynx-group.com Associate Editor Lara J. Lorton Editorial Assistants Jennifer Brandt Cara Guglielmon Production Manager Marie RS Borrelli The Lynx Group President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Human Resources Jennine Leale Associate Director, Content Strategy & 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 Assistant Lora LaRocca Director, Digital Media Anthony Romano Web Content Managers David Maldonado Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Sangenito Senior Project Manager Jini Gopalaswamy Project Coordinators Jackie Luma Deanna Martinez IT Specialist Carlton Hurdle Executive Administrator Rachael Baranoski Administrative Coordinator Stephanie Ramadan 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 Drug Compounding: New Rule a Game Changer for Oncology Practices...........................................................................................7

By Dawn Holcombe, MBA, FACMPE, ACHE

FEATURES Coding and Billing ICD-9 or ICD-10: What Is the Point?…................................................................1

By Karna W. Morrow, CPC, RCC, CCS-P, PCS

Quality Care Shopping for High-Quality, Affordable Oncology Care..................................1

By Carla Balch

Best Practices Providing Social Support to Patients with Cancer...…......................................1 Interview with Vicki Kennedy, LCSW

Regulatory Update Fair Labor Standards Act: Exemptions Review...............................................20

By Robert D. Orzechowski, MBA, SPHR

Physician-Hospital Alignment Series Do’s and Don’ts in Physician-Hospital Alignment, Part 1...............................24

By Max Reiboldt, CPA

Patient Assistance Programs Imbruvica YOU&i Access Program and Support for Patients........................38 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 reimbursment, 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. BPA Worldwide membership applied for September 2013.

June 2014

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Table of Contents

June 2014 • Volume 4 • Number 4

Oncology Practice Management™, ISSN 2164-4403 (print), is published 8 times a year by Engage Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Copyright © 2014 by Engage Healthcare Communications, LLC. All rights reserved. Oncology Practice Management™ is a registered trademark of Engage Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the publisher. Printed in the United States of America.

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 Drug Coding FDA-Approved Medications Used for the Treatment of Lung Cancer....................................................................................................27 Clinical Trial Tracker New Clinical Trials Under Way…......................................................................32 Drug Update Imbruvica (Ibrutinib) the First Bruton’s Tyrosine Kinase Inhibitor Approved for the Treatment of Patients with Relapsed Chronic Lymphocytic Leukemia....................................................................................34

By Lisa A. Raedler, PhD, RPh

EDITORIAL ADVISORY BOARD Editor-in-Chief Dawn Holcombe, MBA, FACMPE, ACHE President DGH Consulting South Windsor, CT Carla Balch CEO, Altos Solutions, a Division of Flatiron Health, Inc New York, NY Peggy Barton, RN Practice Manager Toledo, OH Risë Marie Cleland President Oplinc, Inc Portland, OR

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Patrick A. Grusenmeyer, ScD, FACHE President Christiana Care Health Initiatives Newark, DE

Ruth Linné Lander, FACMPE Practice Administrator Columbus Oncology & Hematology Associates, Inc Columbus, OH

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

Teri U. Guidi, MBA, FAAMA President and CEO Oncology Management Consulting Group Pipersville, PA

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

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

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

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

ONCOLOGY PRACTICE MANAGEMENT

I June 2014

Mary Pat Whaley, FACMPE, CPC Physician Advocate and Consultant www.managemypractice.com Durham, NC

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

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

Primary Endpoint

Secondary Endpoints

• Overall response rate

• • • • • • • •

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

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

NCT#01889186 Reference: ClinicalTrials.gov.

@ 2013 Genentech USA, Inc. All rights reserved. BIO0001961500 Printed in USA.

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

Coding and Billing

ICD-9 or ICD-10: What Is the Point? Continued from the cover One key compo­ nent of any medical document is accurate and complete commu­ nication: document (or report) the most appropriate specifici­ ty about the patient’s condition. This assists in the treatment of patient care, is used for future treatment plans, and, once that clinical information is translat­ ed into data, becomes the database from which healthcare is monitored and measured.

Somewhere along the line, though, this key step has been reduced to a shortcut that has created a database that will eventually shortchange the provider and the patient. Oncologists will often describe the complexity of their patients: the challenging medical decisions required of them each day because of the diverse clin­ ical demographics of their patients, and the frequent but lengthy vis­ its required to manage the myriad of side effects, complications, and even chronic medical conditions they inherit as they become a primary point of medical contact.

The data tell a different story.

The database of diagnosis codes would imply that patients with can­ cer are rarely seen for anything but a primary condition. Multiple high-level evaluation and manage­ ment (E/M) services are required to manage cancer when the spe­ cific site is unreported. The aver­ age oncology claim indicates “lung cancer,” “breast cancer,” or per­ haps “anemia.” The database would imply that less than a handful of patients have neoplasm-related pain, anemia resulting from chemo­ therapy, or even long-term drug use.

As the industry debates the value of implementing the ICD-CM, Tenth Revision (ICD-10-CM), please take

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the time to determine the value of the data from your own office in compari­ son to the real story shared by the cli­ nicians in your office. Run a frequency report on the diagnosis codes reported within the past 6 months. You have been working on clinical documen­ tation improvement for months, but everyone is waiting for the magic “go live” date for ICD-10-CM to test the value of that project. Why wait?

Increased specificity in the reporting process is needed now.

Increased specificity in the report­ ing process is needed now, is available now, and will generate a more accu­ rate database from which the new for­ mula for physician reimbursement will be created. If we are to have any hope of being appropriately reimbursed in the future when we are under a case mix, pay-for-performance, or even quality outcome measurement system, we need accurate data.

Look at that frequency report.

Based only on the data (which is what the payers see), how many patients in your practice were seen to manage their chemotherapyrelated or neoplasm-related pain?

How many were seen for the wellknown side effects: nausea, vom­ iting, fatigue, or neuropathy? How many developed systemic conditions as a result of the treatment and/ or the malignancy? Drill down on anemia—how many patients have anemia as a result of chemothera­ py versus anemia as a stand-alone condition? If you had to project the likelihood of a secondary malignan­ cy or the recurrence of a malignancy from any given primary site, could

ONCOLOGY PRACTICE MANAGEMENT

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you, from the data you have in your practice?

Unfortunately, most could not.

We have developed a habit of link­ ing E/M services to the most generic cancer code available. We endure payer audits focused on our levels of E/M services—focused on our use of modifier 25—and yet we continue to submit generic, unspecified diag­ nosis codes that will continue to raise an audit alert. Imaging studies are ordered for the primary cancer, despite the reality that the magnetic resonance imaging (MRI) really was not about the pancreatic cancer, but about the patient’s complaints of persistent headaches and blurred vision. The MRI was to evaluate for metastases, but the “reason for exam” did not state that. And we will continue to be audited for our “excessive orders.” We will continue to see limits placed on the imaging studies we order, because the data do not support the medical necessity of the current process.

ICD-10-CM may be the best cata­ lyst we have had in decades to clean up the reporting process related to the treatment of this complex patient population. If the specific location of the malignancy is known, report it. When the patient is seen and resources are used to manage the side effects, report them. If resources are expended to evaluate scans, com­ pare treatment plans, and manage the referrals and opinions from multiple providers, translate that paragraph in the medical record into the appropri­ ate diagnosis codes now. The codes exist today.

Do not delay the implementa­ tion of ICD-10-CM content in your practice. Do not focus on the code set; focus on the primary benefit of that code set. You will position your practice to be the one with the data when the new reimbursement model is defined and implemented. l

From the Editor

Drug Compounding: New Rule a Game Changer for Oncology Practices

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

M

anaging the compounding and handling of hazardous drugs has always been com­ plicated, but it is the cornerstone of the care we provide. These drugs offer hope to patients battling can­ cer. Many oncology practices would be surprised to hear, though, that new rules governing the administra­ tion of hazardous drugs like chemo­ therapy are being written in the pharmacy arena. They affect every oncology practice, regardless of size or corporate structure (private or hospital owned).

The US Pharmacopeial Conven­ tion (USP) is a scientific nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines worldwide.

USP’s drug standards are considered enforceable in the United States.

The group is proposing General Chapter <800> (USP 800), a new chapter that addresses the handling of hazardous drugs in healthcare settings. It intends to affect all oncology providers who store, pre­ pare, compound, or administer oncology drugs. This chapter is still in proposal form; commentary and feedback are being accepted this year until July 31.

Why is it important to oncology practices? On many levels, this new regulation may change the opera­ tions, marketing, contracting, and financial structure of oncology delivery in the immediate future.

USP 800 is written to identify safe handling of hazardous drugs for the protection of staff and patients. It is also written to apply to all health­ care settings. Once USP 800 is finalized, it is out there for potential enforcement. Practices that are not

compliant with USP 800 standards could face a loss of market share, adverse publicity, or enforcement obligations.

How can pharmacy regulation affect a medical practice? One might ask how a regulation mostly enforced by state boards of pharmacy might

would be difficult to argue that they should not be followed in any setting • Enforceability: USP chapters numbered below 1000 are con­ sidered enforceable, and those with higher numbers are con­ sidered guidelines. If imple­ mented, USP 800 would be national in scope and apply to healthcare providers of all shapes and sizes (private or hospital-based, pharmacy or physician) • Enforcement: This varies be­ cause the USP does not have its own enforcement body, so most enforcement is accomplished by the US Food and Drug Administration (FDA), Joint Commission, and individual state boards of pharmacy.

Pharmacy regulations differ across states, which is why phy­ sicians are able to dispense in most states, but not all.

What does USP 800 cover? The chapter was created to identify requirements for receipt, storage, mixing, preparing, compounding, dispensing, and administration of HDs to protect the patient, health­ care personnel, and environment.

Details of USP 800 can be found on the USP website.1 Standards out­ lined in USP 800 apply to all per­ sonnel who compound HD prepara­ tions and all places where HDs are prepared (eg, pharmacies, hospitals, and other healthcare institutions, patient treatment clinics, physi­ cians’ practice facilities, and veteri­ narians’ offices). The prior chapter,

New rules governing the administration of hazardous drugs like chemotherapy are being written in the pharmacy arena.

affect a medical practice operating under different oversight and regula­ tion. If a practice has registered within a state as a registered pharma­ cy, then that pharmacy is subject to pharmacy board regulations. Even if a practice were to take the position that these USP 800 standards do not apply to its practice, there are situa­ tions where it might not stand as a valid argument.

• Legislative action: The local state legislature might take action related to the standards set forth in USP 800 and make them law with enforceable deadlines • The court of public opinion: It is stated clearly in USP 800, “There is no acceptable level of personnel exposure to HDs [hazardous drugs].”1 USP 800 standards have been written to protect staff and patients. It

June 2014

Continued on page 10

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Quality Care

Shopping for High-Quality, Affordable…Continued from the cover filters so that healthcare consumers can search for an oncologist or prac­ tice based on the search criteria that are most important to them.

The second word, “best,” is anoth­ er challenge for the healthcare con­ sumer. The word indicates quality, something proven, and the work of a known craftsman or artist. I have had the privilege of working with some of the best oncologists in the nation, so I support the notion of an oncologist as an artist who, with creativity, orders a personal­ ized treatment plan for each patient.

Although the treatment is chosen and administered with great care, how does a patient evaluate the quality or how “best” the treatment and patient experience are?

A student of clinical trials, I believe that one of the most relevant measures of the best care is the clin­ ical success of the chosen treatment (ie, the clinical outcome). “No evi­ dence of disease” being the ultimate goal, a range of clinical outcomes could factor into the decision that determines best care. In addition, the best care is likely proven over a period of time and should be deter­ mined by patients who are qualified to judge the quality of the treatment.

We are individuals and more than the sum of our treatment out­ come; we are mothers, fathers, sisters, brothers, friends, and colleagues with important lives that deserve as little life-threatening disruption as possi­ ble. In addition to clinical outcome, it is also important to consider the overall patient when determining best care. The emotional, financial, and spiritual impact of care on the patient’s life, even accounting for variances in patients’ coping skills, must be evaluated to deem what care is best. In order to make this decision, we must ask patients what they have to say about their care. But where is there a collection of patient data that

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systematically measures the effect of cancer treatment on patients’ emo­ tions, finances, or spirit?

The Patient Care Monitor, for­ merly known as the Cancer Care Monitor,1,2 gathered thousands of patient-reported reviews through a tablet computer in oncology wait­ ing rooms across the United States.

Included in the review was a val­ idated set of questions targeted at emotional distress. The results, which were presented to oncolo­

I believe that one of the most relevant measures of the best care is the clinical success of the chosen treatment (ie, the clinical outcome).

gists, brought a variety of responses, from compartmentalizing a patient’s emotional distress and referring out to a therapist or support group, to hiring clinical psychologists on staff to more holistically approach the range of care. Other initiatives around patient-reported outcomes exist but are still the exception to everyday workflows at many oncol­ ogy practices.

In oncology, professional orga­ nizations striving to improve care have designed, launched, and mea­ sured droves of quality improvement programs over the years. Physicians participating in quality improve­ ment programs (while struggling to see more patients per day) have their day compromised by the dron­ ing impersonal data entry into a paper form or web portal. Though the quality programs are crafted by well-meaning healthcare organiza­

ONCOLOGY PRACTICE MANAGEMENT

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tions, pathway providers, and payers, the physician needs technological assistance to comply with the data collection requirements.

With so many organizations striving to define quality, let us encourage like-minded, quality-fo­ cused groups to come together and agree on 10 metrics. Perhaps we all gather around these metrics to collect, understand, and use the results to make real improvements in quality. As an industry, we then move to the next 10 metrics, and then the next, all moving together successfully around the same defini­ tion of quality, and making wide­ spread, meaningful improvements in patient care and physician reim­ bursement for the achievements.

The fractured approach of so many different definitions (and data-gath­ ering requirements) of quality is stymieing any progress we could be making together if we all paddled in the same direction.

Expanding on the concept of best quality, the cost of the best care can be catastrophic to patients and their families. The financial impact of cancer, even for those with qual­ ity insurance, has been described as life-changing. Patients struggle with decisions on how to spend their hard-earned income or sav­ ings. Financial counselors at prac­ tices are unfortunately tasked with asking a patient to choose between potentially life-saving treatment and college tuition for a child. They somehow are able to have these dif­ ficult discussions in an encouraging and optimistic manner, and each day brave patients and their self­ less families make difficult decisions.

How is this collective experience shared with other patients? Where are these data captured, collected, evaluated, and served back to soci­ ety for consideration?

Continued on page 10

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Quality Care

Shopping for High-Quality, Affordable…Continued from page 8 This brings us to a third concept in my grandmother’s maxim, “Buy the best you can afford.” The term “afford” affects people differently, but in the frame of healthcare, it translates into the ability to stretch to a point that otherwise reason­ able people would find financially uncomfortable. For this measure, there should be understandable, quantifiable, and transparent sourc­ es that provide data on the impact of this financial component—the ability to afford care. A tool that quantifies cost would allow patients to determine the oncology care that is the best they can physically and emotionally afford.

Could the answer be a safe, vetted, unbiased zone of online value-based oncology data, complete with out­ come measurements matched with data on financial burdens to the patient and society? As we struggle in our industry, it is not helpful to complain without offering solutions.

Consider the power of oncology practices, technology partners, pay­ ers, and patients banding together in a politically neutral way to identify first steps. Let’s start with technology that allows healthcare consumers to shop and select providers, define quality, and finally understand the finances of affordability.

The end goal seems lofty, but if

we approach this systematically by solving 1 important concept at a time, by the end of the first year, I believe we will see otherwise dispa­ rate parties all pointed in the same direction (at least conceptually) and committed to advancing the accessibility, quality, and afford­ ability of our oncology system. We should all be part of the solution.

Let’s get started. l

References

1. Fortner B, Okon T, Schwartzberg L, et al. The Cancer Care Monitor: psychometric content evaluation and pilot testing of a computer administered system for screening and quality of life in adult cancer patients.

J Pain Symptom Manage. 2003;26:1077-1092.

2. Abernethy AP, Zafar SY, Uronis H, et al. Validation of the Patient Care Monitor (version 2.0): a review of system assessment instrument for cancer patients.

J Pain Symptom Manage. 2010;40:545-558.

Drug Compounding: New Rule Continued from page 7 USP 797, titled Pharmaceutical Com­pounding–Sterile Prepar­ations, included an allowance for facilities that prepared a “low volume” of HDs, but USP 800 removes that allowance.

It is not just about USP 800; other standards now apply to medical practices, not just hospitals.

USP 800 identifies 10 sources of best practices for handling HDs, stating that where conflicts exist, the most stringent requirements prevail.

These sources include publications and regulations from the Oc­ ­ cupational Safety and Health Ad­ ­ ministration, the National Institute for Occupational Safety and Health, the American Society of HealthSystem Pharmacists, and the Oncology Nursing Society. Many of these regulations have previously been applied to hospital or pharmacy settings and not so much to private practice settings. USP 800 is now bringing all of these requirements to bear on all healthcare facilities,

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including private practices.

Other recent regulations you should consider and review. The Drug Quality and Security Act (DQSA) was signed into law on November 27, 2013. There are 2 primary sections, one addresses compounding quality, and the other addresses drug supply chain securi­ ty. The purpose of the act was to better manage and control drug compounding (especially in out­ sourced settings), improve commu­ nications between the FDA and state regulators (for better manag­ ing of drug-related crises), preserve and protect the practice of tradi­ tional pharmacy compounding in community pharmacies, and create a process for the registration of “outsourcing facilities” (entities engaged in the compounding of sterile drugs). Aspects of DQSA may affect medical practices depending upon state regulations, structure of entity, and engagement with licensed pharmacists. The text

ONCOLOGY PRACTICE MANAGEMENT

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of DQSA is available online.2 What should oncology practices do? It seems fairly certain that USP 800 will be adopted, so it is impor­ tant for oncology practices to read the proposed chapter carefully and provide comments via the appropri­ ate channels by the July 31, 2014, deadline. The proposed chapter is posted online3; click on the link labeled “<800> Hazardous Drugs— Handling in Healthcare Settings” to reach the proposal, presented with numbered lines. Comments may be addressed to Compound ingSL@usp.org, and are more likely to be addressed if accurate line numbers are referenced with the comments. l

References

1. US Pharmacopeial Convention. <800> Hazardous Drugs—Handling in Healthcare Settings. www. usp.org/sites/default/files/usp_pdf/EN/m7808.pdf.

Accessed June 5, 2014.

2. GOVTRACK. H.R. 3204: Drug Quality and Security Act. www.govtrack.us/congress/bills/113/ hr3204#overview. Accessed June 9, 2014.

3. US Pharmacopeial Convention. General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings. www.usp.org/usp-nf/notices/compoundingnotice. Accessed June 5, 2014.

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IncyteCARES: ASSISTING PROVIDERS AND PATIENTS IN OBTAINING ACCESS TO JAKAFI

Visit www.IncyteCARES.com or call 1-855-4-JAKAFI (1-855-452-5234), Monday–Friday, 8 AM–8 PM ET, to learn more about how to connect your patients to IncyteCARES.

Indications and Usage Jakafi is indicated for treatment of patients with intermediate or high-risk MF, including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF. Important Safety Information for Jakafi (ruxolitinib), continued • Serious bacterial, mycobacterial, fungal and viral infections may occur. Active serious infections should have resolved before starting Jakafi. Tuberculosis (TB) has been reported; attention should be given to the possibility of latent or active TB. Observe patients receiving Jakafi for signs and symptoms of infection and initiate appropriate treatment promptly • Progressive multifocal leukoencephalopathy (PML) has been reported with ruxolitinib treatment for myelofibrosis. If PML is suspected, stop Jakafi and evaluate • Advise patients about early signs and symptoms of herpes zoster and to seek early treatment • The three most frequent non-hematologic adverse reactions were bruising, dizziness and headache • A dose modification is recommended when administering Jakafi with strong CYP3A4 inhibitors or in patients with renal or hepatic impairment. Patients should be closely monitored and the dose titrated based on safety and efficacy • Use of Jakafi during pregnancy is not recommended and should only be used if the potential benefit justifies the potential risk to the fetus. Women taking Jakafi should not breast-feed Please see additional Important Safety Information and the Brief Summary of Full Prescribing Information within this ad.

Jakafi is a registered trademark of Incyte Corporation. © 2014, Incyte Corporation. All rights reserved. RUX-1227p

05/14

Table 2: Worst Hematology Laboratory Abnormalities in the Placebo-controlled Studya Jakafi Placebo (N=155) (N=151) Laboratory All All Grade 4 Grades Grade 3 Grade 4 Parameter Gradesb Grade 3 BRIEF SUMMARY: For Full Prescribing Information, see package insert. (%) (%) (%) (%) (%) (%) INDICATIONS AND USAGE Jakafi is indicated for treatment of patients with intermediate or high-risk Thrombocytopenia 69.7 9.0 3.9 30.5 1.3 0 myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential Anemia 96.1 34.2 11.0 86.8 15.9 3.3 thrombocythemia myelofibrosis.

Neutropenia 18.7 5.2 1.9 4.0 0.7 1.3 CONTRAINDICATIONS None.

WARNINGS AND PRECAUTIONS Thrombocytopenia, Anemia and Neutropenia Treatment a Presented values are worst Grade values regardless of baseline b National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 with Jakafi can cause thrombocytopenia, anemia and neutropenia. [see Dosage and Administration (2.1) in Full Prescribing Information]. Thrombocytopenia was generally reversible and was usually managed by Additional Data from the Placebo-controlled Study 25.2% of patients treated with Jakafi and 7.3% of reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary [see Dosage and patients treated with placebo developed newly occurring or worsening Grade 1 abnormalities in alanine transAdministration (2.2) in Full Prescribing Information, and Adverse Reactions]. Patients developing anemia aminase (ALT). The incidence of greater than or equal to Grade 2 elevations was 1.9% for Jakafi with 1.3% may require blood transfusions and/or dose modifications of Jakafi. Severe neutropenia (ANC less than Grade 3 and no Grade 4 ALT elevations. 17.4% of patients treated with Jakafi and 6.0% of patients treated 0.5 X 109/L) was generally reversible. Withhold Jakafi until recovery [see Adverse Reactions]. Perform a pre- with placebo developed newly occurring or worsening Grade 1 abnormalities in aspartate transaminase treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and (AST). The incidence of Grade 2 AST elevations was 0.6% for Jakafi with no Grade 3 or 4 AST elevations. then as clinically indicated [see Dosage and Administration (2.2) in Full Prescribing Information, and Adverse 16.8% of patients treated with Jakafi and 0.7% of patients treated with placebo developed newly occurring or Reactions]. Risk of Infection Serious bacterial, mycobacterial, fungal and viral infections may occur. worsening Grade 1 elevations in cholesterol. The incidence of Grade 2 cholesterol elevations was 0.6% for Jakafi with no Grade 3 or 4 cholesterol elevations.

Active serious infections should have resolved before starting therapy with Jakafi. Tuberculosis has been reported in patients receiving Jakafi for myelofibrosis. Attention should be given to the possibility of latent or DRUG INTERACTIONS Drugs That Inhibit or Induce Cytochrome P450 Enzymes Ruxolitinib is predominantly metabolized by CYP3A4. Strong CYP3A4 inhibitors: The Cmax and AUC of ruxolitinib active tuberculosis. Observe patients receiving Jakafi for signs and symptoms of infection and initiate increased 33% and 91%, respectively, with Jakafi administration (10 mg single dose) following ketoconazole appropriate treatment promptly. PML Progressive multifocal leukoencephalopathy (PML) has been reported 200 mg twice daily for four days, compared to receiving Jakafi alone in healthy subjects. The half-life was also with ruxolitinib treatment for myelofibrosis. If PML is suspected, stop Jakafi and evaluate. Herpes Zoster prolonged from 3.7 to 6.0 hours with concurrent use of ketoconazole. The change in the pharmacodynamic Advise patients about early signs and symptoms of herpes zoster and to seek treatment as early as possible marker, pSTAT3 inhibition, was consistent with the corresponding ruxolitinib AUC following concurrent adminif suspected [see Adverse Reactions]. istration with ketoconazole. When administering Jakafi with strong CYP3A4 inhibitors a dose reduction is ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other recommended [see Dosage and Administration (2.7) in Full Prescribing Information]. Patients should be sections of the labeling: • Myelosuppression [see Warnings and Precautions]; • Risk of Infection [see closely monitored and the dose titrated based on safety and efficacy. Mild or moderate CYP3A4 inhibitors: Warnings and Precautions] Clinical Trials Experience Because clinical trials are conducted under There was an 8% and 27% increase in the C and AUC of ruxolitinib, respectively, with Jakafi administration max widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly (10 mg single dose) following erythromycin, a moderate CYP3A4 inhibitor, at 500 mg twice daily for 4 days, compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The compared to receiving Jakafi alone in healthy subjects. The change in the pharmacodynamic marker, pSTAT3 safety of Jakafi was assessed in 617 patients in six clinical studies with a median duration of follow-up of 10.9 inhibition was consistent with the corresponding exposure information. No dose adjustment is recommended months, including 301 patients with myelofibrosis in two Phase 3 studies. In these two Phase 3 studies, when Jakafi is coadministered with mild or moderate CYP3A4 inhibitors (eg, erythromycin). CYP3A4 patients had a median duration of exposure to Jakafi of 9.5 months (range 0.5 to 17 months), with 88.7% of inducers: The Cmax and AUC of ruxolitinib decreased 32% and 61%, respectively, with Jakafi administration patients treated for more than 6 months and 24.6% treated for more than 12 months. One hundred and (50 mg single dose) following rifampin 600 mg once daily for 10 days, compared to receiving Jakafi alone in eleven (111) patients started treatment at 15 mg twice daily and 190 patients started at 20 mg twice daily. In healthy subjects. In addition, the relative exposure to ruxolitinib’s active metabolites increased approximately a double-blind, randomized, placebo-controlled study of Jakafi, 155 patients were treated with Jakafi. The 100%. This increase may partially explain the reported disproportionate 10% reduction in the pharmacomost frequent adverse drug reactions were thrombocytopenia and anemia [see Table 2]. Thrombocytopenia, dynamic marker pSTAT3 inhibition. No dose adjustment is recommended when Jakafi is coadministered with anemia and neutropenia are dose related effects. The three most frequent non-hematologic adverse reactions a CYP3A4 inducer. Patients should be closely monitored and the dose titrated based on safety and efficacy. were bruising, dizziness and headache [see Table 1]. Discontinuation for adverse events, regardless of USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C: There are no adequate causality, was observed in 11.0% of patients treated with Jakafi and 10.6% of patients treated with placebo. and well-controlled studies of Jakafi in pregnant women. In embryofetal toxicity studies, treatment with Following interruption or discontinuation of Jakafi, symptoms of myelofibrosis generally return to ruxolitinib resulted in an increase in late resorptions and reduced fetal weights at maternally toxic doses. pretreatment levels over a period of approximately 1 week. There have been isolated cases of patients discon- Jakafi should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. tinuing Jakafi during acute intercurrent illnesses after which the patient’s clinical course continued to worsen; Ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses however, it has not been established whether discontinuation of therapy contributed to the clinical course in of 15, 30 or 60 mg/kg/day in rats and 10, 30 or 60 mg/kg/day in rabbits. There was no evidence of teratothese patients. When discontinuing therapy for reasons other than thrombocytopenia, gradual tapering of the genicity. However, decreases of approximately 9% in fetal weights were noted in rats at the highest and dose of Jakafi may be considered [see Dosage and Administration (2.9) in Full Prescribing Information]. Table maternally toxic dose of 60 mg/kg/day. This dose results in an exposure (AUC) that is approximately 2 times 1 presents the most common adverse reactions occurring in patients who received Jakafi in the double-blind, the clinical exposure at the maximum recommended dose of 25 mg twice daily. In rabbits, lower fetal weights placebo-controlled study during randomized treatment. of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. This dose is approximately 7% the clinical exposure at the maximum recommended dose. In Table 1: Adverse Reactions Occurring in Patients on Jakafi in the Double-blind, Placebo-controlled a pre- and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implanStudy During Randomized Treatment tation through lactation at doses up to 30 mg/kg/day. There were no drug-related adverse findings in pups for Jakafi Placebo fertility indices or for maternal or embryofetal survival, growth and development parameters at the highest (N=155) (N=151) dose evaluated (34% the clinical exposure at the maximum recommended dose of 25 mg twice daily).

Adverse All All Nursing Mothers It is not known whether ruxolitinib is excreted in human milk. Ruxolitinib and/or its Reactions Gradesa Grade 3 Grade 4 Grades Grade 3 Grade 4 metabolites were excreted in the milk of lactating rats with a concentration that was 13-fold the maternal (%) (%) (%) (%) (%) (%) plasma. Because many drugs are excreted in human milk and because of the potential for serious adverse Bruisingb 23.2 0.6 0 14.6 0 0 reactions in nursing infants from Jakafi, a decision should be made to discontinue nursing or to discontinue Dizzinessc 18.1 0.6 0 7.3 0 0 the drug, taking into account the importance of the drug to the mother. Pediatric Use The safety and effecHeadache 14.8 0 0 5.3 0 0 tiveness of Jakafi in pediatric patients have not been established. Geriatric Use Of the total number of myelofibrosis patients in clinical studies with Jakafi, 51.9% were 65 years of age and older. No overall differUrinary Tract Infectionsd 9.0 0 0 5.3 0.7 0.7 ences in safety or effectiveness of Jakafi were observed between these patients and younger patients. Renal Weight Gaine 7.1 0.6 0 1.3 0.7 0 Impairment The safety and pharmacokinetics of single dose Jakafi (25 mg) were evaluated in a study in Flatulence 5.2 0 0 0.7 0 0 healthy subjects [CrCl 72-164 mL/min (N=8)] and in subjects with mild [CrCl 53-83 mL/min (N=8)], Herpes Zosterf 1.9 0 0 0.7 0 0 moderate [CrCl 38-57 mL/min (N=8)], or severe renal impairment [CrCl 15-51 mL/min (N=8)]. Eight (8) a National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 b includes contusion, ecchymosis, hematoma, injection site hematoma, periorbital hematoma, vessel puncture site additional subjects with end stage renal disease requiring hemodialysis were also enrolled. The pharmacokinetics of ruxolitinib was similar in subjects with various degrees of renal impairment and in those with hematoma, increased tendency to bruise, petechiae, purpura normal renal function. However, plasma AUC values of ruxolitinib metabolites increased with increasing c includes dizziness, postural dizziness, vertigo, balance disorder, Meniere’s Disease, labyrinthitis d includes urinary tract infection, cystitis, urosepsis, urinary tract infection bacterial, kidney infection, pyuria, bacteria severity of renal impairment. This was most marked in the subjects with end stage renal disease requiring hemodialysis. The change in the pharmacodynamic marker, pSTAT3 inhibition, was consistent with the urine, bacteria urine identified, nitrite urine present e includes weight increased, abnormal weight gain corresponding increase in metabolite exposure. Ruxolitinib is not removed by dialysis; however, the removal f includes herpes zoster and post-herpetic neuralgia of some active metabolites by dialysis cannot be ruled out. When administering Jakafi to patients with Description of Selected Adverse Drug Reactions Anemia In the two Phase 3 clinical studies, median moderate (CrCl 30-59 mL/min) or severe renal impairment (CrCl 15-29 mL/min) with a platelet count time to onset of first CTCAE Grade 2 or higher anemia was approximately 6 weeks. One patient (0.3%) between 100 X 109/L and 150 X 109/L and patients with end stage renal disease on dialysis a dose reduction discontinued treatment because of anemia. In patients receiving Jakafi, mean decreases in hemoglobin is recommended [see Dosage and Administration (2.8) in Full Prescribing Information]. Hepatic reached a nadir of approximately 1.5 to 2.0 g/dL below baseline after 8 to 12 weeks of therapy and then Impairment The safety and pharmacokinetics of single dose Jakafi (25 mg) were evaluated in a study in gradually recovered to reach a new steady state that was approximately 1.0 g/dL below baseline. This pattern healthy subjects (N=8) and in subjects with mild [Child-Pugh A (N=8)], moderate [Child-Pugh B (N=8)], or was observed in patients regardless of whether they had received transfusions during therapy. In the severe hepatic impairment [Child-Pugh C (N=8)]. The mean AUC for ruxolitinib was increased by 87%, 28% randomized, placebo-controlled study, 60% of patients treated with Jakafi and 38% of patients receiving and 65%, respectively, in patients with mild, moderate and severe hepatic impairment compared to patients placebo received red blood cell transfusions during randomized treatment. Among transfused patients, the with normal hepatic function. The terminal elimination half-life was prolonged in patients with hepatic median number of units transfused per month was 1.2 in patients treated with Jakafi and 1.7 in placebo impairment compared to healthy controls (4.1-5.0 hours versus 2.8 hours). The change in the pharmacotreated patients. Thrombocytopenia In the two Phase 3 clinical studies, in patients who developed Grade 3 dynamic marker, pSTAT3 inhibition, was consistent with the corresponding increase in ruxolitinib exposure or 4 thrombocytopenia, the median time to onset was approximately 8 weeks. Thrombocytopenia was except in the severe (Child-Pugh C) hepatic impairment cohort where the pharmacodynamic activity was generally reversible with dose reduction or dose interruption. The median time to recovery of platelet counts more prolonged in some subjects than expected based on plasma concentrations of ruxolitinib. When above 50 X 109/L was 14 days. Platelet transfusions were administered to 4.7% of patients receiving Jakafi administering Jakafi to patients with any degree of hepatic impairment and with a platelet count between and to 4.0% of patients receiving control regimens. Discontinuation of treatment because of thrombo- 100 X 109/L and 150 X 109/L, a dose reduction is recommended [see Dosage and Administration (2.8) in Full cytopenia occurred in 0.7% of patients receiving Jakafi and 0.9% of patients receiving control regimens. Prescribing Information].

Patients with a platelet count of 100 X 109/L to 200 X 109/L before starting Jakafi had a higher frequency of Grade 3 or 4 thrombocytopenia compared to patients with a platelet count greater than 200 X 109/L (16.5% Jakafi is a registered trademark of Incyte Corporation. All rights reserved. versus 7.2%). Neutropenia In the two Phase 3 clinical studies, 1.0% of patients reduced or stopped Jakafi U.S. Patent No. 7,598,257 because of neutropenia. Table 2 provides the frequency and severity of clinical hematology abnormalities © 2011-2013 Incyte Corporation. All rights reserved.

Issued: November 2013 RUX-1326 reported for patients receiving treatment with Jakafi or placebo in the placebo-controlled study.

Best Practices

Providing Social Support to Patients…Continued from the cover of the person’s life, the different domains that affect their ability to participate in their treatment: their emotional health and well­ being, their social experiences and their relationships in their life, their finances. All of those aspects are really so important to their ability to get good quality care. It is an important part of the treat­ ment equation today to include psychosocial care as a part of the treatment itself.

Q: Is the oncology community providing adequate psychosocial support for the oncology population?

Ms Kennedy: It is difficult to determine “What is adequate social care?” Adequate varies person to person. Some people have great­ er needs. Almost 40% of people with cancer experience significant enough distress to impact their abil­ ity to participate well in their treat­ ment. It is hard to say what is ade­ quate anymore. What is important is to be able to…help patients identify what their problems and concerns are, and find them the information and resources that they need in order to quickly help them address those needs and concerns.

Q: What can practice managers and clinical care managers do to ensure that patients and caregivers have access to the support they need?

Ms Kennedy: Practice managers can play a vital role in really iden­ tifying resources in the community that they can provide to patients and families who are coming into the practices. Clinical managers can play an important role in helping to identify what those needs are. We have to ask the patients first what they are concerned about and do that in a consistent way.

Then the practice managers, as long as they are well informed about what is available in the communi­

ty, can provide that information [to patients] in written information, booklets, brochures—ways that can help patients find resources.

stigma for people around cancer.

There is often a stigma, particularly in American society, about asking for help or receiving help in the community. There is also fear and anxiety about the normal kind of reaction in the cancer experience with the thought that “Oh, I have to be tough,” or “I really do not need the help and support that is out there.” Perhaps, also an important barrier is that the healthcare team really does not recognize the impor­ tance of identifying these needs and linking the patients up with the services that could be most helpful.

Q: What insider tips would you share with other members of the cancer patient’s healthcare team to facilitate access to care?

Ms Kennedy: There are a lot of things. As an oncology social worker, I have learned over the years many ways that we can better engage patients and families…in the conversation about their care.

What is it that they need along that cancer journey? More and more we are learning from patients about the cancer experience and what they need. They need help with coping with the cost of care. They need help understanding the com­ plex treatment options that have been provided for them. They may need help managing family, work, or home life—different aspects of coping with their cancer. The best tip I can give to practices is to locate resources, either locally or nationally, that are available to your patients and to the caregivers who are in your practices. Think about how you can better ask the patients in a systematic way about what they need, and then link them up with those important resources.

Do not wait for patients to be in crisis to get them to those services that can be most helpful. l

Vicki Kennedy, LCSW

Q: What can be done to increase the awareness of social support services within the cancer community?

Ms Kennedy: There is, by and large, a lack of awareness that there are support services, and that psy­ chosocial issues are an important part of cancer treatment. There are many, many groups, institutions, and organizations that are working hard to bring awareness to the importance of psychosocial care. It is no longer just a nice thing to do to tell people about support services and get them to the services that they need. It is actually a critical part of quality care to get the best health outcomes.

Q: Are there barriers that prevent patients and caregivers from receiving social support, and, if so, what can be done to overcome these barriers?

Ms Kennedy: Sadly, there are barriers for patients and families to reach services that can be vitally important to their health and wellbeing during the cancer experience.

Often, those barriers are kind of surprising. I think there is still a

June 2014

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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 Benefit 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 (mCRPC) who have previously received docetaxel.

IMPORTANT SAFETY INFORMATION Contraindications – XTANDI (enzalutamide) capsules can cause fetal harm when administered to a pregnant woman based on its mechanism of action. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant.

Warnings and Precautions – In the randomized clinical trial, seizure occurred in 0.9% of patients on XTANDI. No patients on the placebo arm experienced seizure.

Patients experiencing a seizure were permanently discontinued from therapy. All seizures resolved. Patients with a history of seizure, taking medications known to decrease the seizure threshold, or with other risk factors for seizure were excluded from the clinical

    

trial. 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.

Adverse Reactions – The most common adverse drug reactions (≥ 5%) reported in patients receiving XTANDI in the randomized clinical trial were asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% grade 3-4) and in 6% of patients on placebo (no grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients and 2% of patients on placebo. One percent of XTANDI patients compared to 0.3% of patients on placebo died from

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infections or sepsis. Falls or injuries related to falls occurred in 4.6% of XTANDI patients vs 1.3% of patients on 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.

Grade 1 or 2 hallucinations occurred in 1.6% of XTANDI patients and 0.3% of patients on placebo, with the majority on opioid-containing medications at the time of the event.

Drug Interactions: Effect of Other Drugs on XTANDI – Administration of strong CYP2C8 inhibitors can increase the plasma exposure to XTANDI. Coadministration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If coadministration of XTANDI cannot be avoided, reduce the dose of XTANDI. Coadministration of XTANDI with strong or moderate CYP3A4 and CYP2C8 inducers can alter the plasma exposure of XTANDI and should be avoided if possible.

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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 coadministered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

PLEASE SEE BRIEF SUMMARY OF COMPLETE PRESCRIBING INFORMATION ON FOLLOWING PAGES.

XTANDI Access ServicesSM, a component of Astellas Access ServicesSM 1-855-8XTANDI (1-855-898-2634); Fax 1-855-982-6341; XtandiAccess.com ©2014 Astellas Pharma US, Inc. All rights reserved. 076-0153-PM 4/14 Printed in USA XTANDI, Astellas, and the flying star logo are trademarks of Astellas Pharma, Inc.

(continued) Table 1. Adverse Reactions in the Randomized Trial XTANDI N = 800 Grade 1-4 Grade 3-4 (%) (%)

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 ----------------------------XTANDI is indicated for the treatment of patients with metastatic castrationresistant prostate cancer who have previously received docetaxel.

--------------------------------- CONTRAINDICATIONS ------------------------------Pregnancy XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action. 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].

-------------------------- WARNINGS AND PRECAUTIONS ------------------------Seizure In the randomized clinical trial, 7 of 800 (0.9%) patients treated with XTANDI 160 mg once daily experienced a seizure. No seizures occurred in patients treated with placebo. Seizures occurred from 31 to 603 days after initiation of XTANDI. Patients experiencing seizure were permanently discontinued from therapy and all seizures resolved. There is no clinical trial experience re-administering XTANDI to patients who experienced seizures.

The safety of XTANDI in patients with predisposing factors for seizure is not known because these patients were excluded from the trial. 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, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold.

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.

--------------------------------- 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.

In the randomized clinical trial in patients with metastatic castration-resistant prostate cancer who had previously received docetaxel, patients received XTANDI 160 mg orally once daily (N = 800) or placebo (N = 399). The median duration of treatment was 8.3 months with XTANDI and 3.0 months with placebo.

All patients continued androgen deprivation therapy. Patients were allowed, but not required, to take glucocorticoids. During the trial, 48% of patients on the XTANDI arm and 46% of patients on the placebo arm received glucocorticoids.

All adverse events and laboratory abnormalities were graded using NCI CTCAE version 4.

The most common adverse drug reactions (≥ 5%) reported in patients receiving XTANDI in the randomized clinical trial were asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. 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 the randomized clinical trial that occurred at a ≥ 2% absolute increase in frequency in the XTANDI arm compared to the placebo arm.

Table 1. Adverse Reactions in the Randomized Trial XTANDI Placebo N = 800 N = 399 Grade 1-4 Grade 3-4 Grade 1-4 Grade 3-4 (%) (%) (%) (%) General Disorders 50.6 9.0 44.4 9.3 Asthenic Conditionsa Peripheral Edema 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 2.5 17.3 1.8 Musculoskeletal Pain 15.0 1.3 11.5 0.3 Muscular Weakness 9.8 1.5 6.8 1.8 Musculoskeletal 2.6 0.3 0.3 0.0 Stiffness

Placebo N = 399 Grade 1-4 Grade 3-4 (%) (%)

Gastrointestinal Disorders Diarrhea 21.8 1.1 17.5 0.3 Vascular Disorders Hot Flush 20.3 0.0 10.3 0.0 Hypertension 6.4 2.1 2.8 1.3 Nervous System Disorders Headache 12.1 0.9 5.5 0.0 9.5 0.5 7.5 0.5 Dizzinessb Spinal Cord 7.4 6.6 4.5 3.8 Compression and Cauda Equina Syndrome Paresthesia 6.6 0.0 4.5 0.0 4.3 0.3 1.8 0.0 Mental Impairment Disordersc Hypoesthesia 4.0 0.3 1.8 0.0 Infections And Infestations 10.9 0.0 6.5 0.3 Upper Respiratory Tract Infectiond Lower Respiratory 8.5 2.4 4.8 1.3 Tract And Lung Infectione Psychiatric Disorders 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 0.0 Non-pathologic 4.0 1.4 0.8 0.3 Fractures Skin And Subcutaneous Tissue Disorders Pruritus 3.8 0.0 1.3 0.0 Dry Skin 3.5 0.0 1.3 0.0 Respiratory Disorders Epistaxis 3.3 0.1 1.3 0.3 a Includes asthenia and fatigue. b Includes dizziness and vertigo. c Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention. d Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis. e Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

Laboratory Abnormalities In the randomized clinical trial, Grade 1-4 neutropenia occurred in 15% of patients on XTANDI (1% Grade 3-4) and in 6% of patients on placebo (no Grade 3-4). The incidence of Grade 1-4 thrombocytopenia was similar in both arms; 0.5% of patients on XTANDI and 1% on placebo experienced Grade 3-4 thrombocytopenia. Grade 1-4 elevations in ALT occurred in 10% of patients on XTANDI (0.3% Grade 3-4) and 18% of patients on placebo (0.5% Grade 3-4).

Grade 1-4 elevations in bilirubin occurred in 3% of patients on XTANDI and 2% of patients on placebo.

Infections In the randomized clinical trial, 1.0% of patients treated with XTANDI compared to 0.3% of patients on placebo died from infections or sepsis. Infection-related serious adverse events were reported in approximately 6% of the patients on both treatment arms.

Falls and Fall-related Injuries In the randomized clinical trial, falls or injuries related to falls occurred in 4.6% of patients treated with XTANDI compared to 1.3% of patients on 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.

Hallucinations In the randomized clinical trial, 1.6% of patients treated with XTANDI were reported to have Grade 1 or 2 hallucinations compared to 0.3% of patients on placebo. Of the patients with hallucinations, the majority were on opioidcontaining medications at the time of the event. Hallucinations were visual, tactile, or undefined.

----------------------------------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 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].

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 ].

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 ].

-------------------------- USE IN SPECIFIC POPULATIONS -----------------------Pregnancy- Pregnancy Category X [see Contraindications].

XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action. While there are no human or animal 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. 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. 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 800 patients who received XTANDI in the randomized clinical trial, 71 percent were 65 and over, while 25 percent 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 castration-resistant prostate cancer 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].

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].

-------------------------------------- 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 seizures following an overdose.

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- and 13-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).

PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (PATIENT INFORMATION).

• Instruct patients to take their dose at the same time each day (once daily).

XTANDI can be taken with or without food. Each capsule should be swallowed whole. Do not chew, dissolve, or open the capsules.

• Inform patients receiving a GnRH analog that they need to maintain this treatment during the course of treatment with XTANDI. • Inform patients that XTANDI has been associated with an increased risk of seizure. Discuss conditions that may predispose to seizures and medications that may lower the seizure threshold. Advise patients of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others.

• Inform patients that XTANDI may cause dizziness, mental impairment, paresthesia, hypoesthesia, and falls.

• Inform patients that they should not interrupt, modify the dose, or stop XTANDI without first consulting their physician. Inform patients that if they miss a dose, then they should take it as soon as they remember.

If they forget to take the dose for the whole day, then they should take their normal dose the next day. They should not take more than their prescribed dose per day.

• Apprise patients of the common side effects associated with XTANDI: asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION. • Inform patients that XTANDI may be harmful to a developing fetus.

Patients should also be informed that they should use a condom if having sex with a pregnant woman. A condom and another effective method of birth control should be used if the patient is having sex with a woman of child-bearing potential. These measures are required during and for three months after treatment with XTANDI.

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 Issued: August 2012 12A005-ENZ-BRS Rx Only © 2012 Astellas Pharma US, Inc. XTANDI® is a registered trademark of Astellas Pharma Inc.

ONCOLOGY

Regulatory Update

Fair Labor Standards Act: Exemptions Review

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

R

ecent media co­v­­ er­ age of the de­bate surrounding an increased federal minimum wage as well as increased “salary basis” test to determine exempt status has drawn employers’ attention.

Although some claim that these actions are posturings on the part of politicians seeking to further their own party’s agenda and will have little impact on the majority of American workers, the news does provide an opportunity to clarify a few critical points for medical prac­ tice employers.

The federal minimum wage and salary basis test are provisions with­ in the Fair Labor Standards Act (FLSA),1,2 enacted in 1938, which is often referred to as the “Wage and Hour” law. Imagine the labor and employment landscape that must have existed in 1938, including oppressive working rules and con­ ditions, and no worker protections for overtime, minimum wages, child labor, recordkeeping, and numerous other aspects of the employment relationship. The FLSA was also, in effect, an attempt at a national job classification program.

Since its passage, certain jobs and entire industries have been excluded from coverage.2,3 There are regular court decisions on issues of working hours, class action suits regarding the “exempt” status of certain employees, and W-2 versus Form 1099 workers. Exempt status is based largely on income and job description; the classification impacts whether an employee is governed by rules regarding mini­ mum wage and overtime pay.4 It is possible that employers may mis­ classify employees out of ignorance

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or inattention to job details. It is also possible that employers mis­ classify employees as independent contractors. The results of these misclassifications can be disastrous.

Sanctions for violations (inten­ tional or otherwise) can be severe,5 compliance is often uncertain, and most states (or municipalities) even have their own similar—but not always exact—replicas of the FLSA. If you are covered by any of these related statutes or ordinances and the FLSA, you must follow which­ ever requirements are more advan­ tageous to your employees.

The purpose of this article is to review a primary point of concern for medical practice management: the employee’s exempt versus non­ exempt status. We will assume for the purpose of this article that your employing medical practice is cov­ ered by FLSA, and that your workers are, in fact, W-2 employees. The next step, then, is to determine each employee’s status as exempt from FLSA or if they are nonexempt.

The FLSA specifically exempts certain workers and industries from its minimum wage provisions, over­ time requirements, or both. The employee exemptions have some specific, and not-so-specific, stan­ dards (duties tests). Therefore, accurate, current job descriptions are critical to compliance. The main categories of exemptions are executive, administrative, profes­ sional, and outside sales. Readers may recall recent court decisions regarding pharmaceutical repre­ sentatives and their exemption as “outside sales” employees. Other exemptions include computer, highly compensated, and first re­ sponder employees. In addition, if employees are determined to be exempt by virtue of their work (not

ONCOLOGY PRACTICE MANAGEMENT

I June 2014

their job title), they must ordinarily be paid a salary. There is also a salary level test, which is currently $455 weekly. Other rules apply to exempt employees regarding dock­ ing pay for no work, discipline, or garnishment.2-4 Each duties test must be satis­ fied within its own category. The employer cannot choose duties from multiple exempt categories.

Furthermore, the job’s prima­ ry duties are paramount for the exempt determination. Ideally, the job design will require any primary duties to account for more than 50% of the total work time. There is no percentage requirement in the FLSA, but employers are cautioned that having lower percentages of any exempt duties increase the legal risk if challenged. The actual FLSA language is too lengthy to include here, but can be found on the US Department of Labor’s Wage and Hour Division website6; most med­ ical practice employees would have the following exemptions if their duties warranted such an exemp­ tion (Table)4: • Executive. This includes “hire/ fire” authority, management of all or part of the entity, and directing the work of others • Administrative. This includes office or nonmanual work directly related to the manage­ ment or business operations of the employer. It must include the exercise of discretion and independent judgment • Professional. This is divided into 2 sections: learned profes­ sional (LP) and creative profes­ sional (CP). The LP is described as doing work that is intellectu­ al in nature, requiring the con­ sistent exercise of discretion and requiring advanced knowledge.

Regulatory Update

The CP is described as doing work that requires invention, originality, or talent in a recog­ nized field of artistic endeavor.

The detailed rules and exam­ ples used to qualify for these exemptions appear to be specif­ ic.4 Unfortunately, the reality of our work processes, job designs, and shifting responsibilities are often less specific than the written examples. Employers should famil­ iarize themselves with the criteria for each exemption before making a determination about and docu­ menting their decision for FLSA coverage.

Here are a few related issues that may arise in the course of imple­ menting compliance programs for the FLSA4,6,7: • Employees may not waive their rights to the requirements of the law • Only actual time worked (including certain “donning and doffing” time) must be con­ sidered when calculating over­ time. Vacation, holiday, and sick time, for example, are not included in the total hours in a given workweek • Each workweek’s hours are cal­ culated separately in most cases.

• Nonexempt employees must be paid premium pay for hours worked in excess of 40 in a work­ week (not for hours exceeding 8 in a workday). Note that there are exceptions to this 40-hour rule • Employers are generally free, within limits, to establish their own definitions for a workweek and a pay period. A workweek is any consecutive 7-day (168hour) period. A pay period is usually 2 consecutive work­ weeks for nonexempt employees (some employers pay exempt employees monthly) • Compensatory time is general­

Table

Most Medical Practice Employees Could Fall Under the Following Exemptions

Executive Hire/fire authority, some management responsibilities Administrative Office or nonmanual work, related to management, includes exercise of discretion Learned Professional Work is intellectual, requires discretion and advanced knowledge Creative Professional Work requires invention, originality, or talent in an artistic field Source: United States Department of Labor, Wage and Hour Division.

ly not allowed for nonexempt employees in the private sector • Nonexempt employees may be paid a salary, but doing so exposes the employer to some complicated calculations should overtime pay be required. It is prudent to pay nonexempt employees on an hourly basis and to devise adequate controls on overtime • Exempt employees may be paid for time worked above a certain number of hours, but doing so should be a business decision and developed only after a thor­ ough analysis • Employers are not required to have exempt employees track their working time through manual or electronic means.

There may be business reasons (and employee relations rea­ sons) for such a decision.

Recent proposals from mem­ bers of Congress could include an increase to the current salary basis amount of $455 weekly. Should the duties test remain as written, but the salary test increase substantial­ ly, it is possible that many employ­ ees of medical practices may have their exempt status revised and, if then found to be nonexempt, would be eligible for overtime pay going forward.

The FLSA is a critical piece of

June 2014

labor law and must always be taken seriously. The dynamics of the workplace and evolving nature of this law through presidential exec­ utive order, court cases, and con­ gressional amendment demand our constant vigilance for compliance.

No single article on the FLSA can possibly cover all aspects of it, and nothing can replace legal counsel for your human resources policy and practices review. Future articles will focus on other aspects of this important legislation. l

References

1. United States Department of Labor, Wage and Hour Division. Compliance Assistance–Wages and the Fair Labor Standards Act (FLSA). www.dol.gov/ whd/flsa/. Accessed April 29, 2014.

2. United States Department of Labor, Wage and Hour Division. Fact Sheet #17G: Salary Basis Requirement and the Part 541 Exemptions Under the Fair Labor Standards Act (FLSA). www.dol.gov/whd/ regs/compliance/fairpay/fs17g_salary.pdf. Accessed April 29, 2014.

3. United States Department of Labor, Wage and Hour Division. Coverage Under the FLSA. www.flsa.com/ coverage.html. Accessed April 29, 2014.

4. United States Department of Labor, Wage and Hour Division. Fact Sheet #17A: Exemption for Executive, Administrative, Professional, Computer & Outside Sales Employees Under the Fair Labor Standards Act (FLSA). www.dol.gov/whd/regs/com pliance/fairpay/fs17a_overview.pdf. Accessed April 29, 2014.

5. United States Department of Labor, Wage and Hour Division. Poster: Employee Rights Under the Fair Labor Standards Act. www.dol.gov/whd/regs/ compliance/posters/minwage.pdf. Accessed April 29, 2014.

6. United States Department of Labor, Wage and Hour Division. Home Page. www.dol.gov/whd/.

Accessed April 29, 2014.

7. United States Department of Labor, Wage and Hour Division. Overtime Pay. www.dol.gov/whd/ overtime_pay.htm. Accessed April 29, 2014.

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5

Y E AR A NN I V E RS A RY

FIFTH ANNUAL

Navigation and Survivorship Conference September 18-21, 2014 • Walt Disney World Dolphin Hotel • Orlando, FL AONN+ LEADERSHIP PROGRAM DIRECTOR

TARGET AUDIENCE

This educational initiative is directed toward oncology nurse navigators, patient navigators, case managers, care managers, administrators, and social workers whose focus is on cancer care and survivorship.

STATEMENT OF NEED/PROGRAM OVERVIEW

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

AONN+’s Fifth Annual Conference will continue to advance the navigation profession by expanding the scope of educational sessions, networking opportunities, and poster presentations. In addition, this year’s conference will address the evolving challenges of program improvement, the role of personalized medicine, and implementing best practices in navigation, survivorship, and psychosocial care for cancer patients.

EDUCATIONAL OBJECTIVES

After completing this activity, the participant should be better able to: • Describe the evolution of the role of navigation in healthcare • Interpret strategies for navigating diverse patient populations by cancer type and environmental factors • Define methods for providing patient support and guidance in the age of personalized cancer care • Explain how to evaluate best practices regarding survivorship and psychosocial care

NURSING CONTINUING EDUCATION

Global Education Group is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s COA. This educational activity for 15.75 contact hours is provided by Global Education Group.

Nurses should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN CASE MANAGEMENT ASSOCIATION

Application for certification of ACMA hours has been applied for and is pending decision.

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

This activity is co-provided by Global Education Group and Center of Excellence Media, LLC.

NATIONAL ASSOCIATION OF SOCIAL WORKERS

This program has been submitted and is pending approval by the National Association of Social Workers for continuing education contact hours.

DISCLOSURE OF CONFLICTS OF INTEREST

Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouse/life partner who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

AMERICANS WITH DISABILITIES ACT

Event staff will be glad to assist you with any special needs (ie, physical, dietary, etc).

Please contact Patrice Melluso prior to the live event at pmelluso@the-lynx-group.com and 516-835-6529.

REGISTER TODAY! www.regonline.com/AONN2014

AGENDA

*

Thursday, September 18 12:30 pm - 1:30 pm 3:30 pm - 4:30 pm 5:30 pm - 8:00 pm

Start a Subcommittee Meeting (non–CE-certified activity) Start an AONN Chapter Meeting (non–CE-certified activity) Welcome Reception and Keynote Session (non–CE-certified activity)

4:45 pm - 5:45 pm

Friday, September 19 Navigators Exploring Xtra Tracks (N.E.X.T.) Day

Breakfast/Session 1 sponsored by Celgene Corporation (non–CE-certified activity) 8:15 am - 9:15 am Session 2 sponsored by Lilly Oncology (non–CE-certified activity) 9:30 am - 10:30 am Session 3 sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. (non–CE-certified activity) 10:45 am - 11:45 am Session 4 (non–CE-certified activity) 12:00 pm - 1:00 pm Lunch/Session 5 sponsored by Millennium: The Takeda Oncology Company (non–CE-certified activity) 1:15 pm - 2:15 pm Session 6 (non–CE-certified activity) 2:30 pm - 3:30 pm Session 7 (non–CE-certified activity) 3:45 pm - 4:45 pm Session 8 (non–CE-certified activity) 4:45 pm - 6:15 pm Poster Question and Answer Session in the Exhibit Hall (non–CE-certified activity) 6:30 pm - 9:30 pm Heroes of Hope AONN+ Family Event at Epcot Center Extra registration fee required for this event. (non–CE-certified activity) 7:00 am - 8:00 am

TM

Saturday, September 20

Meet the Experts Breakfast in the Exhibit Hall (non–CE-certified activity) 8:00 am - 8:15 am Welcome, Introductions & Business Update (non-CE-certified activity) - Lillie D. Shockney, RN, BS, MAS; Sharon Gentry, RN, MSN, AOCN, CBCN 8:00 am - 9:00 am General Session 1: Finding Humor Where You Least Expect It: An Oncology Nurse Navigator’s Experiences with Breast Cancer Lillie D. Shockney, RN, BS, MAS 9:00 am - 10:00 am General Session 2: Sex, Chemo, and Rock & Roll - Penny Daugherty, RN, MS, OCN 10:00 am - 11:00 am General Session 3: Navigation and Survivorship Standards —Are You Ready for Your Commission on Cancer Accreditation? Virginia Vaitones, MSW, OSW-C 11:00 am - 12:00 pm General Session 4: Multiorgan Site Navigation - Libby F. Daniels, RN, OCN 12:00 pm - 1:15 pm Poster Award Winner Announcements, Presentations, and Luncheon in the Exhibit Hall (non–CE-certified activity) 1:15 pm - 2:15 pm General Session 5: Pediatric Oncology Navigation and Survivorship - Kathy Ruble, RN, CRNP, PhD 2:15 pm - 3:15 pm General Session 6: Medical Home and Quality Accreditations Update - Maureen Lowry, RN, BSN, OCN; John Sprandio, MD 3:15 pm - 5:30 pm Exhibit Hall Open 3:15 pm - 3:30 pm Break in the Exhibit Hall (non–CE-certified activity) 3:30 pm - 4:30 pm Breakout Session 1 (Choose one of the following sessions) • Basic Navigation (0-2 years) - Britta Newcomer, RN 7:00 am - 8:00 am

6:00 pm - 10:00 pm

• Intermediate Navigation (3-5 years) - Lucy Gansauer, RN, MSN, CPSO, OCN - Elaine Sein, RN, BSN, OCN, CBCN • Advanced Navigation (5+ years) - Sharon Gentry, RN, MSN, AOCN, CBCN • Administrators - Lisa Shalkowski, RN, BSN, MSHA Breakout Session 2 (Choose one of the following sessions) • Breast Cancer Navigation and Survivorship • Hematologic Malignancies Navigation and Survivorship - Peg Rummel, RN, MHA, OCN • Head, Neck, and Neurologic Cancers Navigation and Survivorship - Tamara Bowen, RN, BSN, MHA • Gynecologic Cancers Navigation and Survivorship - Carol Cherry, MSN, RN, AOCNS, APNG Heroes of Hope AONN+ 2nd Annual Gala Extra registration fee required for this event. (non–CE-certified activity) TM

Sunday, September 21

Breakfast in the Exhibit Hall (non–CE-certified activity) 7:45 am - 8:00 am Welcome - Lillie D. Shockney, RN, BS, MAS; Sharon Gentry, RN, MSN, AOCN, CBCN 8:00 am - 8:45 am General Session 6: Sharing Best Practices - Mandi Pratt-Chapman, MA 8:45 am - 9:30 am General Session 7: Lay Navigation - Jean B. Sellers, RN, MSN 9:30 am - 10:45 am General Session 8: Utilizing EPIC to Successfully Navigate Patients - Lisa DelPizzo, RN, MSN, CCM, CBPN-IC; Danielle Guillama, RN, BSN, OCN 10:45 am - 12:00 pm Exhibit Hall Open 10:45 am - 11:00 am Break in the Exhibit Hall (non–CE-certified activity) 11:00 am - 12:15 pm Breakout Session 3 (Choose one of the following sessions) • Lung Cancer Navigation and Survivorship - Caryn M. Vadseth, RN, BSN, OCN • Prostate Cancer Navigation and Survivorship - Frank dela Rama, RN, MS, AOCNS • Gastrointestinal/Colorectal Cancer Navigation and Survivorship - Allyson Foor; Gail Sullivan, RN, BS • Melanoma Navigation and Survivorship - Krista M. Rubin, MS, RN, FNP-C 12:15 pm - 1:30 pm Lunch/General Session 9: Cancer Support Community/ UF Health Cancer Center Pilot Program - Linda House, RN, BSN, MSN; Diane Robinson, PhD 1:30 pm - 2:30 pm General Session 10: Sexuality and Intimacy - Michael L. Krychman, MD, FACOG 2:30 pm - 3:30 pm General Session 11: Doctor, Doctor Lend Me Your Ear - Marisa C. Weiss, MD 3:30 pm - 3:45 pm Closing Remarks - Lillie D. Shockney, RN, BS, MAS; Sharon Gentry, RN, MSN, AOCN, CBCN 7:00 am - 7:45 am

*Agenda subject to change.

Complete agenda and faculty information available on our website at AONNonline.org

*

Blackout Times

†

Thursday, September 18 8:00 am - 8:00 pm Friday, September 19 6:30 am - 8:00 pm

Saturday, September 20 6:30 am - 8:00 pm Sunday, September 21 6:30 am - 8:00 pm

Please note that organizations may not hold functions during the defined “blackout” times unless approved by AONN+.

AONN+ will strictly enforce the blackout times. Failure to have approval to hold any event in these established time frames may result in a fine and exclusion from all AONN+ events.

†

AONN2014ConfAd Asize_60914

Physician­­­­–Hospital Alignment Series

Do’s and Don’ts in Physician-Hospital Alignment, Part 1

By Max Reiboldt, CPA, President/CEO, Coker Group, Alpharetta, GA

Part 1 of this 3-part series focuses on pretransactional due diligence and structural design processes as they pertain to physician–hospital alignments. Part 2 of this series will address governance and compensation plans; the final installment will discuss ongoing relationships and planning for a potential “divorce.”

T

he alignment of physicians with hospitals and health sys­ tems is increasingly challeng­ ing in today’s healthcare climate. In the past, many physicians viewed hospitals as potential partners with endless channels of money by which they could augment their previous private practice incomes. Notwith­ standing the compliance concerns with this approach, the economic realities are that hospitals do not have excess funds to pay physi­ cians—at least not at the levels that many physicians expect. Moreover, the regulatory requirements of pay­ ing at fair market value and commer­ cially reasonable rates prevail in every instance.

Despite these challenges, inter­ est in alignments continues to expand. And the necessity of maintaining a strong and diverse medical staff versus the threat of losing critical team members and the subsequent closure of a busi­ ness line often results in hospitals/ health systems making de­ cisions and promises they may not other­ wise make. Accordingly, let’s brief­ ly examine some of the key areas of consideration that must occur to prevent hospitals and physicians from falling into arrangements that are unlikely to succeed.

24

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Pretransactional Due Diligence Before formulating the transac­ tion, both the hospital and the physi­ cian group must be reasonably certain that they are comfortable with part­ nering. Often, this results from an initial review of the landscape (stage

The alignment of physicians with hospitals and health systems is increasingly challenging in today’s healthcare climate.

1). Hospitals will engage consulting firms to complete a landscape review, which involves nonthreatening in­ teractions between the physicians and hospital leadership in explorato­ ry discussions. It is at this stage that specific issues are identified; even more importantly, an exact model is designed. That model could range from limited to moderate to fuller forms of alignment.

The initial review of the land­ scape should encompass some basic financial analysis to consider the historical performance of the prac­ tice. The analysis should also begin to explore what the practice will look like posttransaction through a financial pro forma, which will have a great deal to do with the model that has been selected. If multiple models are under consideration, each should have its own financial pro forma.

Once the basic analysis is com­

ONCOLOGY PRACTICE MANAGEMENT

I June 2014

pleted and the decision is made to move forward into transactional development (stage 2), a more detailed financial analysis should be prepared; this could be prepared by an independent party. That inde­ pendent party should also be knowl­ edgeable in fair market value testing for commercially reasonable rates of compensation for physicians employed by nonprofit hospitals or integrated delivery systems. The financial analysis will ultimately lead to a completed pro forma. The pro forma analysis will address many things, not the least of which will be the hospital or delivery system’s return on investment. The fullfledged pro forma analysis will lead to the development of a term sheet that memorializes (not legally bind­ ing) the key financial terms of the transaction.

Assuming the processes continue to go well, an independent appraisal will also be needed in order to deter­ mine the fair market value of the assets and other related items of value that are included in the trans­ action. Depending upon the struc­ ture of the transaction, the areas of consideration could range from the entire practice entity to certain com­ ponents of the practice, such as physician and staff workforce remaining in place. The indepen­ dent appraisal should be specific in response to the actual structure of the proposed transaction. For exam­ ple, if the transaction is a joint equi­ ty model, the appraisal would only be for a minority interest (assuming that the hospital is only buying a minority interest) of the practice. If it is a professional services agree­ ment, there will likely be very little upfront value exchange, with the

Physician–Hospital Alignment Series

exception of the ancillary assets, which are often purchased by the hospital.

Finally, as a part of the pretrans­ actional due diligence, the hospital/ health system should complete an operational assessment of the prac­ tice or other healthcare entity. This would only be needed if they are acquiring all or most of the practice or the related ancillary service, such as an ambulatory surgery center.

Typically, a hospital/health system will be equipped with its own inter­ nal resources to review all areas of operations, or they will engage an independent expert to complete that operational assessment; the opera­ tional assessment often will include a procedural coding audit.

The pretransitional due diligence process involves many facets to allow the hospital and health system to gain full undersactional of what they are getting into. From there, the parties can move toward a welldesigned and legally compliant alignment transaction.

Structural Design Another key facet toward the suc­ cessful development of a physician– hospital alignment relationship is the actual design of the model. As briefly discussed, there are myriad models; each has its pros and cons, from both the hospital and physician perspec­ tives. It is the job of the experts (often independent consultants and attorneys) who are assisting the prac­ tice and the hospital to point out the pros and cons of each model and, ultimately, to build consensus as to the best model for the particular transaction. Flexibility in model development is a key overarching point of view in achieving a positive result. Although employment is often the preferred model and is the outcome of the majority of transac­ tions, this arrangement should not be forced on the physicians.

Key economic and noneconomic

terms and conditions should be con­ sidered. Ultimately, these will be for­ malized in the definitive agreements; prior to that, a term sheet or letter of intent (LOI) or memo of understand­ ing should detail these terms and conditions. Often, we separate these into 3 major classifications: • Economic • Governance/leadership • Unwind provisions

forma process. For example, if the hospital acquires the ancillary ser­ vices from the practice as a part of the alignment transaction and they choose to convert these to hospital outpatient department (HOPD) billing structure for Medicare and Medicaid, and they move these out of the actual integrated entity, those performance results cannot be con­ sidered in order to determine the physicians’ compensation within the alignment model. However, the hos­ pital should certainly consider the impact of having these assets and being able to realize this revenue going forward. It should also be noted that often this revenue (under HOPD rates) is much better than that paid to private practices. In short, the overall return on invest­ ment (“downstream revenue”) is better for the hospital. Although this should be considered in the overall impact analysis, it cannot be a part of the actual direct transaction for legal and compliance purposes.

Finally, within the structural design and assuming all of these prior analy­ ses have been thoroughly reviewed, and both parties are still interested in proceeding (note that at any point during this process either party can drop out or change the transaction structure), the definitive agreement drafting should be completed. This should include utilization of legal counsel and the consultant’s support to formulate the actual legal docu­ ments that will be executed at closing.

Such legal documents will vary, but usually will include an asset purchase agreement, or, if the entity (or a part of the entity) is being purchased, a stock purchase agreement. Other agreements could be tied to manage­ ment services, operating agreements, employment agreements, professional services contracts, etc. Again, these are all a part of the definitive agree­ ment process that must be ultimately decided upon and responded to, based upon the actual model structure. l

It is the job of the experts who are assisting the practice and the hospital to point out the pros and cons of each model and, ultimately, to build consensus.

With the term sheet and LOI draft in place, these major areas of review have been considered and are a signif­ icant part of the overall foundation that is being formed. (It should be noted that several of the items discussed under pretransactional due diligence would be completed simul­ taneously with the matters we are discussing at this point under struc­ tural design.)

Next, an additional financial anal­ ysis should be considered. While analysis under pretransactional due diligence is absolutely essential, another financial analysis—the “impact analysis”—should be com­ pleted by the hospital. This is done by the hospital as an internal docu­ ment that incorporates the overall contributions that the transaction will entail—meaning that there are some portions of the transaction that will likely not appropriately (or legally) be considered within the pro

June 2014

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*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

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11/10

Drug Coding Supplied by RJ Health Systems

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

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

Associated ICD-9-CM codes for the treatment of lung cancer: 162 Malignant neoplasm of trachea, bronchus, and lung 162.0 Trachea

Cartilage of trachea

Mucosa of trachea 162.2 Main bronchus

Carina

Hilus of lung 162.3 Upper lobe, bronchus or lung 162.4 Middle lobe, bronchus or lung 162.5 Lower lobe, bronchus or lung 162.8 Other parts of bronchus or lung

Malignant neoplasm of contiguous or overlapping sites of bronchus or lung whose point of origin

cannot be determined 162.9 Bronchus and lung, unspecified

FDA approved for lung cancer

Compendia-listed off-label use for Possible CPT ® lung cancer administration codes

Generic (brand) name

HCPCS code - code description

amifostine (Ethyol)

J0207 - Injection, amifostine, 500 mg

√

96374

Bacillus CalmetteGuerin (BCG vaccine)

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

√

90471, 90472

Bacillus CalmetteGuerin (TheraCys, Tice BCG)

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

√

51720

Bacillus CalmetteGuerin (TheraCys, Tice BCG)

J9031 - BCG (intravesical), per instillation

√

51720

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Drug Coding

28

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FDA approved for lung cancer

Compendia-listed off-label use for Possible CPT ® lung cancer administration codes

Generic (brand) name

HCPCS code - code description

bevacizumab (Avastin)

J9035 - Injection, bevacizumab, 10 mg

bleomycin (Blenoxane)

J9040 - Injection, bleomycin sulfate, 15 units

√

96401, 96409

carboplatin (Paraplatin)

J9045 - Injection, carboplatin, 50 mg

√

96409, 96413, 96415

ceritinib (Zykadia)

C9399 - Unclassified drugs or biological (hospital outpatient use ONLY); J8999 - Prescription drug, oral, chemotherapeutic, not otherwise specified

cetuximab (Erbitux)

J9055 - Injection, cetuximab, 10 mg

√

96413, 96415

cisplatin (Platinol AQ)

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

√

96409, 96413, 96415

crizotinib (Xalkori)

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

√

N/A

crizotinib (Xalkori)

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

√

N/A

cyclophosphamide (Cytoxan)

J8530 - Cyclophosphamide, oral, 25 mg

√

N/A

cyclophosphamide (Cytoxan)

J9070 - Cyclophosphamide, 100 mg

√

96409, 96413, 96415

docetaxel (Taxotere)

J9171 - Injection, docetaxel, 1 mg

√

96413

doxorubicin HCl (Adriamycin)

J9000 - Injection, doxorubicin hydrochloride, 10 mg

√

96409

doxorubicin (Doxil)

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

√

96413

epirubicin (Ellence)

J9178 - Injection, epirubicin hydrochloride, 2 mg

√

96409, 96413

erlotinib (Tarceva)

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

√

N/A

erlotinib (Tarceva)

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

√

N/A

etoposide (Vepesid)

J8560 - Etoposide, oral, 50 mg

√

N/A

etoposide (Etopophos, Toposar)

J9181 - Injection, etoposide, 10 mg

√

96413, 96415

ONCOLOGY PRACTICE MANAGEMENT

I June 2014

96413, 96415

√

N/A

√

Drug Coding

FDA approved for lung cancer

Compendia-listed off-label use for Possible CPT ® lung cancer administration codes

Generic (brand) name

HCPCS code - code description

fluorouracil (Adrucil)

J9190 - Injection, fluorouracil, 500 mg

gefitinib (Iressa)

J8565 - Gefitinib, oral, 250 mg

√

N/A

gemcitabine (Gemzar)

J9201 - Injection, gemcitabine hydrochloride, 200 mg

√

96413

ifosfamide (Ifex)

J9208 - Injection, ifosfamide, 1 gram

√

96413, 96415

irinotecan (Camptosar)

J9206 - Injection, irinotecan, 20 mg

√

96413, 96415

lomustine (CeeNu)

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

√

N/A

lomustine (CeeNu)

S0178 - Lomustine, oral, 10 mg

√

N/A

mechlorethamine HCl (Mustargen)

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

√

96409

methotrexate (Trexall)

J8610 - Methotrexate, oral, 2.5 mg

√

N/A

methotrexate

J9250 - Methotrexate sodium, 5 mg

√

96372, 96374, 96401, 96409, 96450

methotrexate

J9260 - Methotrexate sodium, 50 mg

√

96372, 96374, 96401, 96409, 96450

mitomycin (Mutamycin)

J9280 - Injection, mitomycin, 5 mg

√

96409

oxaliplatin (Eloxatin)

J9263 - Injection, oxaliplatin, 0.5 mg

√

96413, 96415

√

96409

paclitaxel protein-bound J9264 - Injection, paclitaxel particles protein-bound particles, 1 mg (Abraxane)

√

96413

paclitaxel (Taxol)

J9265 - Injection, paclitaxel, 30 mg

√

96413, 96415

panitumumab (Vectibix)

J9303 - Injection, panitumumab, 10 mg

pemetrexed (Alimta)

J9305 - Injection, pemetrexed, 10 mg

√

96409

porfimer sodium (Photofrin)

J9600 - Injection, porfimer sodium, 75 mg

√

96409

tamoxifen (Nolvadex)

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

√

N/A

tamoxifen (Nolvadex)

S0187 - Tamoxifen citrate, oral, 10 mg

√

N/A

√

June 2014

I

96413, 96415

www.OncPracticeManagement.com

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29

Drug Coding

FDA approved for lung cancer

Compendia-listed off-label use for Possible CPT ® lung cancer administration codes

Generic (brand) name

HCPCS code - code description

temozolomide (Temodar)

J8700 - Temozolomide, oral, 5 mg

√

N/A

teniposide (Vumon)

Q2017 - Injection, teniposide, 50 mg

√

96413, 96415

topotecan (Hycamtin)

J8705 - Topotecan, oral, 0.25 mg

√

N/A

topotecan (Hycamtin)

J9351 - Injection, topotecan, 0.1 mg

√

96413

trastuzumab (Herceptin)

J9355 - Injection, trastuzumab, 10 mg

√

96413, 96415

vinBLAStine (Velban)

J9360 - Injection, vinblastine sulfate, 1 mg

√

96409

vinCRIStine (Vincasar PFS)

J9370 - Vincristine sulfate, 1 mg

√

96409

vinorelbine (Navelbine)

J9390 - Injection, vinorelbine tartrate, per 10 mg

√

96409

*When billing a nonclassified medication using a CMS 1500 claim form you must include both the HCPCS code (ie, J8999 for Xalkori) in Column 24D and the drug name, strength, and NDC (National Drug Code) in Box 19 or 24A in order to ensure appropriate reimbursement.

Please note : Check with payer regarding correct placement of Medication Information in Box 19 or 24A. References • HCPCS Level II Expert 2014 • Current Procedural Terminology (CPT ®) 2014 (copyright 2014 American Medical Association.

All rights reserved. CPT is a registered trademark of the American Medical Association) • ICD-9-CM for Professionals Volumes 1 & 2, 2014 • FDA-approved indication (from product Prescribing Information) • Compendia references available upon request • www.ReimbursementCodes.com powered by RJ Health Systems International, LLC, Rocky Hill, Connecticut • CMS (Centers for Medicare and Medicaid Services) CPT ® indicates Current Procedural Terminology ; 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 30

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ONCOLOGY PRACTICE MANAGEMENT

I June 2014

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

rjhealthsystems.com

Clinical Trial Tracker

New Clinical Trials Under Way

T

he following clinical trials are currently recruiting patients with renal cell carcinoma (RCC) for inclusion in several investigations. Each trial description includes the NLM Identifier to use as refer­ ence with ClinicalTrials.gov.

1

Neoadjuvant Pazopanib in RCC The purpose of this phase 2 study is to evaluate the effect of neo­ adjuvant pazopanib on disease response and recurrence and to estab­ lish predictive biomarkers of drug activity in patients with histologically confirmed, localized RCC. The study will examine complete response and partial response associated with pazo­ panib at 8 weeks, and is expected to enroll 56 patients. Patients aged ≥18 years with nonmetastatic, clinical stage II RCC and no evidence of extranodal involvement are eligible to participate if other criteria are met.

The primary outcome for this study is response rate after 8 weeks of neo­ adjuvant treatment with pazopanib.

Secondary outcome measures include recurrence-free survival, number of adverse events, and the impact of pazopanib on surgical approach.

Study locations include New York, North Carolina, and Texas. For more information, contact Gayle Grigson, RN, at 919-966-4432 or gayle_grig son@med.unc.edu, or Donna Rowe, RN, at 919-966-7359 or donna_ rowe@med.unc.edu. The NLM Identifier is NCT01361113.

2

Pazopanib Versus Temsi­roli­ mus in Poor-Risk Clear Cell RCC This randomized, phase 2, openlabel study compares pazopanib with temsirolimus in the treatment of patients with clear cell RCC.

32

I

Pazopanib inhibits the growth of blood vessels that supply nutrients necessary for tumor growth, while temsirolimus blocks the growth of cancer cells. The study will assess the efficacy and safety of each drug, and is expected to enroll 90 patients.

Participants will be allocated to receive 800 mg of pazopanib orally once daily or 25 mg of temsirolimus by infusion for 30 to 60 minutes weekly.

Evaluations will occur at baseline, prior to treatment, and every 8 weeks.

Patients who are aged ≥18 years with pathologic evidence of metastat­ ic or locally advanced RCC with a clear cell component and disease state measurable by Response Eva­l­ uation Criteria in Solid Tumors are eligible to participate in the study if other criteria are met. The primary outcome is progression-free survival (PFS), measured every 8 weeks from baseline to disease progression. PFS is defined as the time from initiation of the study drug to time of first disease progression. Radiologic studies using computed tomography or magnetic resonance imaging will be performed every 8 weeks to evaluate response.

This study will be conducted at the University of Texas MD Anderson Cancer Center in Houston. For more information, contact Nizar M. Tannir, MD, Principal Inves­tigator, at 713-792-2830. The NLM Identifier is NCT01392183.

3

Safety, Pharmacokinetics, and Effectiveness of AGS-16C3F Monotherapy in RCC In this phase 1, open-label, multi­ center study, investigators are evalu­ ating the safety, pharmacokinetics, and effectiveness of AGS-16C3F monotherapy in patients with RCC of clear cell or papillary histology.

This study aims to establish a safe dose of AGS-16C3F by intravenous infusion and to assess safety and effi­

ONCOLOGY PRACTICE MANAGEMENT

I June 2014

cacy in 2 expanded cohorts. The first cohort will include patients with clear cell histology, and the second cohort will include patients with papillary histology. The study expects to recruit 72 patients. To be eligible for study participation, patients should be aged ≥18 years, have a histologically confirmed diag­ nosis of metastatic RCC, have mea­ surable disease according to Response Evaluation Criteria in Solid Tumors, and meet additional criteria.

The primary outcome measure of the study is incidence of adverse events within a 24-month time frame. Secondary outcomes include incidence of antibody formation and the measurement of tumor response.

The study will be conducted in New York, Washington, and Michigan.

For more information about the trial, contact Agensys Clinical Research and Development at 424-280-5000 or clinical@agensys.com. The NLM Identifier is NCT01672775.

4

Cyberknife Radiosurgery in RCC The purpose of this phase 2, open-label study is to evaluate the role of radiosurgery in patients with clinically localized primary RCC. This study is expected to enroll 46 patients. Participants will receive radiation doses based on the size of the tumor. Treatment will take 3 to 4 days, but no more than 14 days over­ all. To be eligible for this study, patients must be aged ≥18 years, have histologic evidence of stage I RCC with a tumor size of ≤8 cm, have at least 1 gold fiducial placed in or around the tumor, and meet addition­ al inclusion and exclusion criteria.

The primary outcome of this study is to determine freedom from local tumor progression at 6 months in patients treated with CyberKnife radiosurgery. Secondary outcome mea­

Clinical Trial Tracker

sures include the impact of therapy on quality of life and an evaluation of adverse events. This study is being conducted at Beth Israel Deaconess Medical Center in Boston. For more information, contact Irving D. Kaplan, MD, at 617-667-2345 or ikaplan@ caregroup.harvard.edu, or Nordine Benhaga, MD, at 617-667-4679 or nbenhaga@bidmc.harvard.edu. The NLM Identifier is NCT01890590.

5

Hydroxychloroquine Before Surgery in Patients with Primary RCC The purpose of this phase 1 study is to determine whether the use of hydroxyc­hloroquine before ne­phrec­ tomy in patients with primary RCC will facilitate the elimination of can­ cer cells; another goal is to examine the degree to which the study drug affects the patient’s immune system.

Biologic markers of autophagy in tumor and normal tissues, such as peripheral blood mononuclear cells and renal parenchyma, will be mea­ sured. Biologic markers will also be measured 1 month after surgery.

Patients who are aged ≥19 years with stage I to IV primary or meta­ static RCC with a planned nephrec­ tomy are eligible to participate in the study if additional criteria are met.

This study is expected to enroll 20 patients and will be conducted at the University of Pittsburgh Medical Center, PA. For more information, contact Jodi K. Maranchie, MD, at 412-605-3019 or maranchiejk@ upmc.edu, or Kimberly Jones, RN, BSN, at 412-623-2764. The NLM Identifier is NCT01144169.

6

Panobinostat and Everolimus in Patients with Metastatic or Unresectable RCC The purpose of this phase 1/2, open-label, interventional study is to determine optimal dosing and potential side effects of panobin­ ostat administered together with everolimus in patients with meta­

static or unresectable RCC who did not respond to previous treatment with sunitinib malate or sorafenib tosylate. Patients in the first treat­ ment arm will receive panobinostat orally once daily on days 1, 3, 4, 8, 10, and 12, and oral everolimus once daily on days 1 to 21.

Treatment repeats every 21 days in the absence of disease progression or severe toxicity. This study is expected to enroll 48 patients.

To be eligible for participation, patients should be aged ≥18 years with a histologically confirmed diagnosis of metastatic or unresectable RCC, pre­ dominant clear cell component, and metastatic disease that has progressed within 6 months of stopping treat­ ment; additional inclusion and exclu­ sion criteria must be met. This study will be conducted in New York at the Roswell Park Cancer Institute in Buffalo and the University of Roches­ ter Medical Center. For more informa­ tion, contact Roberto Pili, Principal Investigator, at 877-275-7724 or roberto.pili@roswellpark.org. The NLM Identifier is NCT01582009.

ment with at least 1 previous therapy (sunitinib, pazopanib, sorafenib, tivozanib), and who have no history of other carcinomas within the past 5 years are eligible to participate in the study if additional criteria are met.

Study locations include Alabama, California, and Massa­ chusetts. For more information, contact Manoj Jivani at mjivani@traconpharma. com, or Bonne Adams at badams@ traconpharma.com. The NLM Identifier is NCT01806064.

8

ASONEP in the Treatment of Refractory RCC The objective of this phase 2, multicenter, open-label, single-arm study is to assess the efficacy, safety, and tolerability of ASONEP (sonep­ cizumab/LT1009) monotherapy in the treatment of patients with refrac­ tory RCC. It is estimated that the study will recruit 39 patients, and the treatment arm will consist of ASONEP 15 mg/kg administered by intravenous infusion over 90 minutes once a week every 4 consecutive weeks of patients’ treatment cycle.

The primary outcome measure is pro­ gression-free survival evaluated at 8 weeks. The study will utilize a 2-cohort design; enrollment of cohort 2 will proceed depending on the rate of progression-free survival in cohort 1. Secondary outcome measures include safety and tolerability, mea­ sured as the incidence and frequency of adverse events.

To be eligible for the study, patients must be aged ≥18 years with unresect­ able and locally advanced recurrent or metastatic RCC, have histological evidence of clear cell RCC, demon­ strate disease measurable by Response Evaluation Criteria in Solid Tumors, and meet other inclusion and exclu­ sion criteria. Study locations include California, South Carolina, and Tennessee. For more information, contact France LaPierre-Holme, Study Director, at 858-678-0800. The NLM Identifier is NCT01762033. l

7

Dose Escalation of TRC105 in Combination with Axitinib in Patients with Advanced RCC The goal of this phase 1, openlabel study is to determine the opti­ mal phase 2 dose for TRC105 when administered in combination with standard-dose axitinib in patients with advanced RCC. The study also assesses the safety and tolerability of TRC105 as part of this combination therapy. The primary outcome mea­ sure of this study is to determine the maximum tolerated dose of TRC105 in combination with axitinib during a 1-year time frame. The secondary outcome is to assess plasma TRC105 concentration at specific time points.

It is estimated that 18 patients will be enrolled in this study. Patients who are aged ≥18 years with histolog­ ic evidence of advanced RCC whose disease has progressed following treat­

June 2014

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Drug Update

Imbruvica (Ibrutinib) the First Bruton’s Tyrosine Kinase Inhibitor Approved for the Treatment of Patients with Relapsed Chronic Lymphocytic Leukemia

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

C

hronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, is a cancer of B-cell lymphocytes, which originate in the bone mar­ row, develop in the lymph nodes, and normally fight infection by pro­ ducing an immune response.1,2 In CLL, excess B-cells accumulate in the bone marrow and blood, where they crowd out healthy blood cells.2 The Leukemia & Lymphoma Society has estimated that more than 15,500 Americans were diag­ nosed with CLL in 2013.3 The inci­ dence of CLL increases significantly among people aged ≥50 years; only a small fraction of adults are diagnosed in their 30s or 40s.3 The majori­ ty of patients who are diagnosed with CLL are asymptomatic, and the diagnosis is made as a result of a routine blood test that shows a high white blood cell count.4 As it advances, CLL can cause swollen lymph nodes, an enlarged spleen, anemia, and infections.2 The prognosis for patients with CLL varies significantly based on their disease subtype and risk sta­ tus, with survival duration rang­ ing from approximately 1 year to more than 20 years.5 According to the American Society of Clinical Oncology, the 5-year overall surviv­ al rate for patients with CLL of all stages is approximately 79%.5 Early-stage CLL is typically not treated, whereas patients with symp­ Copyright © 2014 American Health & Drug Benefits. All rights reserved.

34

I

tomatic intermediate- or high-risk CLL are usually receiving chemo­ therapy combined with a targeted monoclonal antibody drug, either rituximab or another CD-20 target­ ed agent.6 Studies comparing treat­ ment with chemotherapy, such as fludarabine or the combination of fludarabine and cyclophosphamide, with chemoimmunotherapy (fludar­ abine and rituximab) have shown that rituximab-containing combina­

“Rarely does a drug come along with so much potential to help CLL patients….

I have been impressed with the promising and durable response rates we have seen in patients.”

—John C. Byrd, MD tions significantly improve complete response rates, remission duration, and overall survival of previously untreated patients with CLL.7 In November 2013, the US Food and Drug Administration (FDA) approved obinutuzumab (Gazyva) in combination with chlorambu­ cil for the treatment of patients with previously untreated CLL.8 Obinutuzumab is a humanized monoclonal antibody that targets

ONCOLOGY PRACTICE MANAGEMENT

I June 2014

CD20 on the surface of CLL cells.9 There is no consensus regard­ ing the management of patients with relapsed and refractory CLL. Treatment decisions are based on several factors, including the timing of relapse, the patient’s age, disease extent, overall health status, and previous therapies.10 Agents that are frequently used (either alone or in combination) in the relapsed and/ or refractory CLL setting include alemtuzumab, bendamustine, chlor­ ambucil, fludarabine, ofatumu­ mab, and rituximab.11 As a chronic illness, the cost bur­ den associated with CLL is signifi­ cant. A recent published cost analy­ sis was conducted in Germany using both the direct and indirect costs of CLL.12 European investigators found that the total per-patient cost for patients with CLL was €9753 (approximately $13,500) annually compared with €4807 (approximate­ ly $6600) annually for individuals in the control group with the same age and sex. In this study, the economic burden associated with CLL was primarily driven by inpatient and pharmaceutical costs. From a socie­ tal perspective, productivity loss was the highest cost driver associated with a diagnosis of CLL.12

Ibrutinib for Previously Treated Patients with CLL On February 12, 2014, the FDA accelerated the approval of an expanded indication for ibruti­ nib (Imbruvica; Pharmacyclics) for patients with CLL who have received at least 1 previous therapy.13 A few

Drug Update

months earlier (in November 2013), the FDA accelerated its approval of ibrutinib for the treatment of patients with mantle-cell lymphoma who had received at least 1 previous therapy.13 Ibrutinib is the first FDAapproved drug designed to target Bruton’s tyrosine kinase (BTK), a protein necessary for the growth and survival of B-cells.14 The FDA’s accelerated approval of ibrutinib for CLL was based on a multicenter, single-arm study of 48 patients with previously treat­ ed CLL.13,15 The primary end point of this trial was overall response rate.13,15 (The analysis used for the approval of ibrutinib for CLL exclud­ ed data for an additional 34 patients in the trial who received ibrutinib 840 mg daily and 3 patients with small lymphocytic lymphoma.16) John C. Byrd, MD, Director of the Division of Hematology at the Ohio State University Comprehensive Cancer Center in Columbus, and a prin­cipal investigator in the ibruti­ nib CLL trial, stated, “Rarely does a drug come along with so much potential to help CLL patients….I have been impressed with the prom­ ising and durable response rates we have seen in patients.”16

Mechanism of Action Ibrutinib is a small-molecule inhibitor of BTK, a signaling mol­ ecule of the B-cell antigen recep­ tor and cytokine receptor path­ ways.15 As an irreversible covalent inhibitor, ibrutinib continues to inhibit BTK even after the drug is metabolized.17 Preclinical studies have demonstrated that ibrutinib prevents the activation of down­ stream pathways affected by BTK, promotes cancer-cell apoptosis, and inhibits cell proliferation.18 Dosing and Administration In patients with CLL who have received at least 1 previous therapy, the recommended dose and schedule

Table 1 Ibrutinib for CLL Dose Modifications for Adverse Reactions Nonhematologic Dose modification postrecovery in patients toxicity event with CLL, starting dose, 420 mg First

Restart at 420 mg daily

Second

Restart at 280 mg daily

Third

Restart at 140 mg daily

Fourth

Discontinue ibrutinib therapy

CLL indicates chronic lymphocytic leukemia.

Source: Imbruvica (ibrutinib) prescribing information; 2014.

Clinical Trials Pivotal Phase 2 Study The safety and efficacy of ibrutinib for the treatment of patients with CLL were demonstrated in a phase 1b/2 open-label, multicenter trial.

This trial included 48 patients with CLL who had previously received multiple therapies.15 In this study, ibrutinib was given orally, 420 mg daily, in continu­ ous 28-day cycles until disease pro­ gression.15 The primary end point of this phase 2 study was overall response rate, which was defined as partial response and complete response. Tumor response was eval­ uated by an Independent Review Committee using a modified version of the International Workshop on CLL criteria.15

for ibrutinib is 420 mg orally once daily. Ibrutinib should be admin­ istered at the same time each day, and should be swallowed whole with water. The capsules should not be opened, broken, or chewed.15 Table 1 summarizes ibrutinib dose modification guidelines for patients with any grade ≥3 nonhematologic toxicity, grade ≥3 neutropenia with infection or fever, or grade 4 hema­ tologic toxicities. Ibrutinib may be reinitiated at the starting dose after symptoms of toxicity have resolved to grade 1 or to baseline.15 Because ibrutinib is primari­ ly metabolized by the cytochrome (CY) P450 enzyme 3A, it should not be coadministered with strong or moderate CYP3A inhibitors.

The concomitant use of strong CYP3A inhibitors that are taken on a long-term basis (eg, rit­onavir, indinavir, nelfinavir, saquinavir, boceprevir, telaprevir, nefazodone) is not recommended.15 Increased drug exposure is also expected in patients with hepatic impairment; however, there are insufficient data to recommend a dose of ibrutinib in patients with baseline hepatic impairment.15 Less than 1% of the ibrutinib dose is excreted renally.15 Exposure to ibrutinib is not altered in patients with creatinine clearance (CrCl) of >25 mL/min. No data exist for patients with severe renal impair­ ment (CrCl <25 mL/min) or for patients on dialysis.15

June 2014

Patient population The median age of the 48 patients with CLL evaluated for this trial was 67 years (range, 37-82 years).15 Most patients were male (71%) and Caucasian (94%). All of the patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The patients’ median time since the diagnosis of CLL exceeded 6 years (80 months). These patients had received 1 to 12 (median, 4) previous therapies for CLL.15 Efficacy In this phase 2 study of ibruti­ nib in patients with relapsed CLL, Continued on page 36

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Drug Update

Imbruvica (Ibrutinib) the First Bruton’s…Continued from page 35 Table 2 Selected Adverse Events of Patients with CLL Receiving Ibrutinib System organ class/ All grades, % Grade 3 or 4, % adverse events (N = 48) (N = 48) Blood disorders Thrombocytopenia 71 10 Neutropenia 54 27 Infections/infestations Sinusitis 21 6 Skin infection 17 6 Pneumonia 10 8 Vascular disorders Hypertension 17 8 Musculoskeletal/connective tissue disorders Musculoskeletal pain 27 6 CLL indicates chronic lymphocytic leukemia.

Source: Imbruvica (ibrutinib) prescribing information; 2014.

the overall response rate was 58.3% (95% confidence interval, 43.2%72.4%).15 All were partial responses.

The duration of response for these patients with CLL ranged from 5.6 months to 24.2+ months. The medi­ an duration of response was not reached at the time of the FDA’s approval of the drug for CLL.15 An increase in lymphocyte counts, defined as a ≥50% increase from baseline and above absolute lymphocyte count of 5000/mcL, was observed in 77% of patients with CLL who received ibrutinib in this phase 2 study. Isolated lymphocyto­ sis occurred during the first 4 weeks of ibrutinib therapy and resolved after a median of 23 weeks (range, 1-104+ weeks).15 RESONATE: Phase 3 Study As a condition for the accelerated approval of ibrutinib for patients with CLL, the FDA instructed the drug manufacturer to submit the results of phase 3 randomized clinical trials to the FDA. In January 2014, the manufacturer of the drug notified the FDA that based on the favorable

36

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results of a planned interim analysis, the phase 3 RESONATE clinical trial that compared ibrutinib and ofa­ tumumab for patients with CLL was ended early.16,19 This phase 3 clinical trial randomized patients with pre­ viously treated CLL or with small lymphocytic lymphoma who were not considered candidates for treat­ ment with purine analog-based treat­ ments to receive either ibrutinib or the anti-CD20 monoclonal antibody ofatumumab.19 The results of this interim analysis showed significant improvements in progression-free sur­ vival and overall survival with ibruti­ nib compared with ofatumumab for patients with previously treated CLL in this phase 3 trial.16,19

Adverse Events The 48 previously treated CLL patients who received ibrutinib in the phase 2 clinical trial received 420 mg daily for a median of 15.6 months.15 Adverse reactions that occurred at a frequency of ≥20% included thrombocytopenia (71%, all grades), diarrhea (63%), bruising (54%), neutropenia (54%), upper

ONCOLOGY PRACTICE MANAGEMENT

I June 2014

respiratory tract infection (48%), anemia (44%), fatigue (31%), musculoskeletal pain (27%), rash (27%), pyrexia (25%), constipation (23%), peripheral edema (23%), arthralgia (23%), nausea (21%), stomatitis (21%), sinusitis (21%), and dizziness (21%).15 The most common grade 3 or grade 4 nonhematologic adverse reactions were pneumonia (8%), hypertension (8%), atrial fibrillation (6%), sinusitis (6%), skin infection (6%), dehydration (6%), and mus­ culoskeletal pain (6%; Table 2).15,16 Of the 48 patients with CLL, 5 discontinued ibrutinib as a result of adverse reactions in the phase 2 trial: 3 patients with infections and 2 patients with subdural hema­ tomas.15 Of the patients with CLL who received ibrutinib, 13% expe­ rienced adverse reactions that led to dose reduction. In 38% of patients, uric acid levels shifted from nor­ mal to elevated during the study, including 4% of patients with val­ ues >10 mg/dL.15

Warnings and Precautions Ibrutinib has no contraindica­ tions.15 Hemorrhage. Bleeding events, including bruising of any grade, were observed in 63% of patients with CLL who received 420 mg of ibru­ tinib daily.15 Of the patients with CLL, 6% had grade ≥3 bleeding events, including subdural hemato­ ma, gastrointestinal bleeding, and hematuria. Clinicians should con­ sider the benefit-risk of ibrutinib in patients who require antiplatelet or anticoagulant therapies, and the benefit-risk of withholding ibrutinib for at least 3 to 7 days before and after surgery depending on the pro­ cedure and the risk of bleeding.15 Infections. Fatal and nonfatal in­ fections occurred in the clinical trial of ibrutinib in patients with CLL.15 At

Drug Update

least 35% of patients with CLL had grade ≥3 infections. Clinicians should regularly monitor patients who are receiving ibrutinib for signs of fever and infections and should evaluate the patients promptly.15 Myelosuppression. Grade 3 or 4 cytopenias, including neutrope­ nia (27%) and thrombocytopenia (10%; Table 2), were reported in the patients with CLL receiving ibrutinib.15 Patients should undergo monthly complete blood cell counts while taking ibrutinib.15 Renal toxicity. Serious and even fatal cases of renal failure have occurred with ibrutinib.15 Increases in creatinine levels up to 1.5 times the upper limit of normal (ULN) occurred in 23% of patients with CLL receiving ibrutinib and from 1.5 to 3 times the ULN in 4% of patients with CLL. Patients receiv­ ing ibrutinib should undergo period­ ic creatinine level monitoring and should maintain hydration.15 Secondary primary malignancies.

Other malignancies, including skin cancers (8%) and other types of car­ cinomas (2%), have been observed in patients with CLL who have received ibrutinib.15 Embryo-fetal toxicity. Based on animal studies, ibrutinib can cause fetal harm when administered dur­ ing pregnancy. Women should be advised to avoid becoming pregnant while taking ibrutinib.15

Specific Populations Pregnant women. Ibrutinib has been assigned Pregnancy Category D. Based on animal data, ibrutinib can cause fetal harm when adminis­ tered to a pregnant woman.15 Nursing mothers. Ibrutinib has not been studied in nursing mothers.

It is not known whether this agent is excreted in human breast milk.

Because many drugs are excreted in human milk and because of the

diseaseinformation/leukemia/chroniclymphocyticleu kemia/causesriskfactors/. Accessed March 3, 2014.

3. Leukemia & Lymphoma Society. Incidence: how common is CLL? www.lls.org/#/diseaseinformation/ leukemia/chroniclymphocyticleukemia/incidence/.

Accessed March 3, 2014.

4. Leukemia & Lymphoma Society. Chronic lym­ phocytic leukemia: signs and symptoms. www.lls.org/ diseaseinformation/leukemia/chroniclymphocyticleu kemia/signssymptoms/. Accessed March 3, 2014.

5. Cancer.net. Leukemia–chronic lymphocytic–CLL: statistics. Updated February 18, 2014. www.cancer. net/cancer-types/leukemia-chronic-lymphocytic-cll/ statistics. Accessed March 4, 2014.

6. Cancer.net. Leukemia–chronic lymphocytic–CLL: treatment options. www.cancer.net/cancer-types/leu­ kemia-chronic-lymphocytic-cll/treatment-options.

Accessed March 4, 2014.

7. Leukemia & Lymphoma Society. Chronic lympho­ cytic leukemia: clinical trials. www.lls.org/diseasein formation/leukemia/chroniclymphocyticleukemia/ clinicaltrials/. Accessed March 3, 2014.

8. US Food and Drug Administration. FDA approves Gazyva for chronic lymphocytic leukemia. Press release. November 1, 2013. www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/ucm373209.htm.

Ac­cessed November 29, 2013.

9. Gazyva (obinutuzumab) injection [prescribing information]. South San Francisco, CA: Genentech, Inc; November 2013.

10. Leukemia & Lymphoma Society. Chronic lym­ phocytic leukemia: before treatment. www.lls.org/#/ diseaseinformation/leukemia/chroniclymphocyticleu kemia/beforetreatment/. Accessed March 3, 2014.

11. Leukemia & Lymphoma Society. Chronic lym­ phocytic leukemia: chemotherapy and drug therapy. www.lls.org/#/diseaseinformation/leukemia/chron iclymphocyticleukemia/treatment/chemotherapy drugtherapy/. Accessed March 3, 2014.

12. Blankart CR, Koch T, Linder R, et al. Cost of illness and economic burden of chronic lymphocytic leukemia. Orphanet J Rare Dis. 2013;8:32.

13. US Food and Drug Administration. FDA ap­­proves Imbruvica to treat chronic lymphocytic leukemia. Press release. February 12, 2014. www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/ucm385764.htm.

Accessed March 14, 2014.

14. Lymphoma Research Foundation. Breakthrough ther­ apy ibrutinib effective in CLL and MCL lymphomas.

August 2013. www.lymphoma.org/site/pp.asp?c=bkLT­ KaOQLmK8E&b=8756085. Accessed March 11, 2014.

15. Imbruvica (ibrutinib) capsules [prescribing informa­ tion]. Sunnyvale, CA: Pharmacyclics; February 2014.

16. Inman S. FDA approves ibrutinib for chronic lymphocytic leukemia. OncLive. February 12, 2014. www.onclive.com/web-exclusives/FDA-ApprovesIbrutinib-for-CLL#sthash.bNUKV3Wo.dpuf.

Accessed March 11, 2014.

17. Woyach J. BTK inhibition and the mechanism of action of ibrutinib. Targeted Oncology. August 20, 2013. www.targetedonc.com/targeted-communications/ Dr-Woyach-on-BTK-Inhibition-and-the-Mechanismof-Action-of-Ibrutinib. Accessed December 16, 2013.

18. Akinleye A, Chen Y, Mukhi N, et al. Ibrutinib and novel BTK inhibitors in clinical development.

J Hematol Oncol. 2013;6:59.

19. US Food and Drug Administration. Ibrutinib (Imbruvica). Updated February 13, 2014. www.fda. gov/Drugs/InformationOnDrugs/ApprovedDrugs/ ucm385878.htm. Accessed March 11, 2014.

20. Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32-42.

21. ClinicalTrials.gov. Ibrutinib combination. Search results. http://clinicaltrials.gov/ct2/results?term= ibrutinib+combination+&Search=Search. Accessed March 11, 2014.

potential for serious adverse events with ibrutinib, a decision should be made to discontinue nursing or to discontinue taking ibrutinib, with the importance of the drug to the mother kept in mind.15 Pediatric patients. The safety and efficacy of ibrutinib in pediatric patients have not been established.

Older patients. In the clinical trial of ibrutinib for the treatment of patients with CLL, 52% of patients were aged ≥65 years. When older and younger patients were com­ pared, no overall differences in efficacy were observed. However, a higher number of adverse events were reported in older patients (aged ≥65 years). Specifically, grade ≥3 adverse events occurred more often among older patients compared with among younger patients (80% vs 61%, respectively).15

Conclusion Ibrutinib, the first FDA-approved BTK inhibitor, offers clinicians and previously treated patients with CLL an effective and safe treatment option. This once-daily oral agent has demonstrated a high response rate, as well as a favorable toxicity profile, in patients with relapsed CLL. Because ibrutinib has a favorable therapeutic index, its use in combination with other agents for the treatment of patients with CLL and other hemato­ logic malignancies is currently being explored.16,20 Examples include an ongoing study combining ibrutinib with bendamustine and ri­tuximab for patients with relapsed or refractory CLL and a study combining ibruti­ nib with rituximab for patients with relapsed or refractory mantle-cell lymphoma.21 l References

1. Leukemia & Lymphoma Society. Chronic lymphocyt­ ic leukemia. www.lls.org/#/diseaseinformation/leukemia/ chroniclymphocyticleukemia/. Accessed March 3, 2014.

2. Leukemia & Lymphoma Society. Chronic lympho­ cytic leukemia: causes and risk factors. www.lls.org/

June 2014

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37

Patient Assistance Programs

Imbruvica YOU&i Access Program and Support for Patients This article is the first in a series of 5 articles to run in Oncology Practice Management on patient assistance programs. The information below—highlighting an assistance program for patients who are prescribed Im­­bruvica—was provided by Phar­ macyclics, Inc, and Janssen Biotech, Inc.

YOU&i Access Programs When Pharmacyclics and Janssen Biotech set out to launch Imbruvica in the United States, they prioritized one goal above all others: providing access support to patients who are prescribed Imbruvica. Improving access for patients is challenging due to the complicated nature of the reimbursement landscape. What might help improve access for a patient with commercial insurance may not be available or allowed for a patient with government-funded insurance. Patients may have high­er out-of-pocket costs in certain months versus others. To help make access to Imbruvica simple, conve­ nient, and easy for a variety of patients, Pharmacyclics and Janssen Biotech created a unique set of patient support programs called YOU&i Access programs.

For commercial patients, Phar­ macyclics and Janssen Biotech offer the YOU&i Access Instant Savings Program to help with out-of-pocket

expenses for Imbruvica. This pro­ gram enables eligible patients with commercial insurance to pay a copay of $25 per month,a regardless of income level. The patient can use as much or as little as they need in each month.

Improving access for patients is challenging due to the complicated nature of the reimbursement landscape. What might help improve access for a patient with commercial insurance may not be available or allowed for a patient with governmentfunded insurance.

For patients experiencing insur­ ance coverage decision delays, Pharmacyclics and Janssen Biotech offer the YOU&i Start Program. This program offers eligible patients who have been prescribed Imbruvica for a US Food and Drug Ad­­ministration-

approved indication, and who are experiencing an insurance coverage decision delay of greater than 5 busi­ ness days, a free 30-day supply of Imbruvica. Under appropriate cir­ cumstances, an additional 30-day supply may be provided. The free product is offered to eligible patients without any purchase contingencies or other obligations.

For uninsured patients, the Johnson & Johnson Patient As­ ­ sistance Foundation, an indepen­ dent, nonprofit organization, may offer assistance with accessing Imbruvica to eligible patients who qualify based on financial need (income requirement of 600% of the federal poverty level).

Lastly, for all patients with chronic lymphocytic leukemia (CLL) and mantle-cell lymphoma (MCL), Pharmacyclics and Janssen Biotech support third-party copay assistance foundations, organizations, and other efforts to help any patients gain access to appropriate care and therapies.

Pharmacyclics and Janssen Biotech have supported and continue to sup­ port third-party foundations to assist patients living with CLL or MCL. For more information, visit www. youandiaccess.com or call 877-8773536. l Month refers to a 30-day supply subject to a maxi­ mum benefit, 12 months after activation or 12 month­ ly fills (1-year supply), whichever comes first, unless the maximum dollar benefit has been reached. Not valid for patients enrolled in Medicare or Medicaid. a

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

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ONCOLOGY PRACTICE MANAGEMENT

I June 2014

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