OPM August 2014 by Value-Based Cancer Care

www.OncPracticeManagement.com

AUGUST 2014

VOLUME 4 • NUMBER 5

Oncology Practice Management ™

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

Bringing the Future into the Present: Disaster Planning for the Oncology Office By Mariana S-B Lamb, MS, with contributions from Richard Levine, MD

very medical practice is at risk for a natural or man-made disaster. Future events cannot be predicted, but re sponses to such events can be. Any medical professional who has worked through a disaster can tell you either how glad they are that the practice had a disaster plan in place, or how they regret the practice was not prepared for such a risk. A serious crisis—fire, weather event, health crisis, or something else—disContinued on page 8

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

anaging oncology is a challenge from many perspectives. Physicians balance a patient’s medical condition with his or her medical benefit structure as well as physical, mental, social, and financial situation,

and strive for the best possible solution. When considering reimbursement models, there is a fine line between a physician choosing the best option based on a patient’s needs versus choosing one Continued on page 6

Survey Reveals Drawbacks to Participation in ACA Exchanges By Rosemary Frei, MSc

he challenges involved with the start of implementation of the Affordable Care Act (ACA)’s insurance exchange program are evident in the responses to an April 2014 survey by the Medical Group Management Association (MGMA).1 There were 728 respondents to the survey, representing more than 40,000 physicians. A majority (59.4%) of respondents viewed ACA insurance

exchanges as being un favorable to their prac- Allison Brennan, MPP tices, and most said that payment rates are no higher than those offered from traditional commercial products or traditional Medicare. Furthermore, 87.6% reported difficulty identifying whether patients had ACA exchange coverage. Most respondents also said that it is more difficult than Continued on page 12

From the publishers of

INTEGRATING ONCOLOGISTS, PAYERS, AND THE ENTIRE CANCER CARE TEAM

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Head August 2014 • Volume 4 • Number 5

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 Directors, Client Services Lou Lesperance llesperance@the-lynx-group.com Zach Ceretelle zceretelle@the-lynx-group.com Editorial Directors Dalia Buffery dbuffery@the-lynx-group.com Anne Cooper acooper@the-lynx-group.com Associate Editor Lara J. Lorton Editorial 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 Mike Kodada 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 Defining the Boundaries of Oncology Management......................................1 By Dawn Holcombe, MBA, FACMPE, ACHE

FEATURES Disaster Planning Bringing the Future into the Present: Disaster Planning for the Oncology Office…........................................................................................1 By Mariana S-B Lamb, MS, with contributions from Richard Levine, MD

ACA Exchange Implementation Survey Reveals Drawbacks to Participation in ACA Exchanges.....................1 By Rosemary Frei, MSc

DEPARTMENTS FDA Update..….................................................................................................15 Clinical Trial Tracker New Clinical Trials Under Way......................................................................... 16 Patient and Provider Access The 90-Day Grace Period: What Providers Need to Know............................24

By Sydney Abbott, JD

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.

August 2014

www.OncPracticeManagement.com

Table of Contents

August 2014 • Volume 4 • Number 5

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 Wealth Management New IRA Rollover Rules Issued by the IRS........................................................25 By Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF

Drug Coding FDA-Approved Medications for the Treatment of Leukemia..........................................................................................................28 Drug Update Zykadia (Ceritinib) Approved for the Treatment of Patients with Crizotinib-Resistant ALK-Positive Non–Small-Cell Lung Cancer..............................................................................................................36 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

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 August 2014

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

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From the Editor

Defining the Boundaries of Oncologyâ&#x20AC;ŚContinued from the cover based on a fixed menu of care choices determined by a payer. WellPoint Cancer Care Quality Program Treatment Pathways is a reimbursement model being rolled out in 6 states this year with the intent to cover the full Dawn Holcombe, WellPoint network by MBA, FACMPE, ACHE the middle of 2015; it is also implementing the program through its subsidiary, AIM Specialty Health. The program is initially offering specific approved treatment regimens for breast, colorectal, and nonâ&#x20AC;&#x201C;small-cell lung cancer. WellPoint intends to pay oncologists a set fee for enrolling patients in one of the approved subset of treatments in its program. The company notes that it used external oncology experts in developing the program. Each oncologist will need to consider his or her own perspective on the program; however, some concerns related to new reimbursement models such as the above include the following: Lack of local collaboration with physicians. Numerous collaborative programs and pilots are in development across the nation among physician groups, state oncology associations, and employers and health plans that fund the complex oncology care patients need, including laboratory work; pharmacy; imaging; and inpatient, outpatient, and emergency services at hospitals. A hallmark of these programs must continue to be an interactive discussion and analysis of results and care patterns between physicians and the purchasers. Limited scope and focus: oncology management affects a myriad

of services and resources. Effective management of oncology treatment and disease involves far more than the choice of the drugs used to treat the disease. The patient and his or her disease will react in different ways to the treatments, and each will experience symptoms and side effects that require active medical management and monitoring. This management will incur costs of imaging, diagnostics, sometimes screening and marker testing, and probably urgent care issues that may incur emergency department visits or hospitalizations. These should be taken into consideration in payment models. A narrow definition of cost. Many programs developed external to the oncology medical community and marketed to purchasers such as health plans and employers focus on narrowing treatment choices to reduce overall cost. Cost for these programs, however, is usually defined as total dollars expended for pharmaceuticals. Programs that offer an approved list of regimens are not designed to address the total cost of care or to engage local physicians in seeking more comprehensive oncology management of total costs of care. Lack of clinical trial presence. In medical communities, clinical guidelines and pathways all include recognition of the value of participation in clinical trials as a viable treatment option. Clinical trial participation should be considered as part of any reimbursement model. Transparency of evidence and decision process for approved regimens. The medical community utilizes well-established clinical guidelines and pathways. These involve both rigorous academic discussion and hundreds of practicing community oncologists, academic

ONCOLOGY PRACTICE MANAGEMENT

I August 2014

oncologists, and other board-certified physicians in the review process. Reimbursement models should involve a transparent review process with an appropriate level of breadth, depth, and physician input. Description as a pathway program. Oncology physicians exercise rigorous medical decision-making in matching appropriate treatments to individual patients and their specific disease. Many oncology electronic medical records are now tracking the decision process and providing information and alternatives depending upon the state of the patient and his or her disease. Electronic pathway programs exist and are being used across the country as part of the treatment decision process. A true pathway for clinical treatment involves those numerous branches of decision-making, with clinically relevant choices at each decision point. With national concern being expressed by so many actively treating physicians and state associations regarding changes to oncology reimbursement models, and so many more advanced alternatives that do actively engage and collaborate with the treating physician community, oncology reimbursement models should continue to be reviewed and revisited. If you are in a state where a program is being unveiled, you may wish to talk with colleagues and consider what alternatives exist or what medical concerns are present. Ultimately, participation is a practitionerâ&#x20AC;&#x2122;s choice. Discussion of quality and value options, and asking for transparency and accountability in revealing choices and narrowing of treatment options, are universal and appropriate discussion points for the physicians who, at the end of the day, are responsible to the patients who trust them. l

Now enrolling: MURANO study Investigating the Selective BCL-2 Inhibitor GDC-0199/ABT-199 in Chronic Lymphocytic Leukemia GDC-0199/ABT-199 is an investigational agent that has not been approved by regulatory agencies.

A Phase III Study of GDC-0199/ABT-199 Plus Rituximab Compared With Bendamustine Plus Rituximab in Patients With Relapsed or Resistant Chronic Lymphocytic Leukemia (CLL)

GDC-0199/ABT-199 + rituximab

Phase III Relapsed or resistant CLL (N=370)

GDC-0199/ABT-199 continued for 2 years or until disease progression

Bendamustine + rituximab Randomize Primary Endpoint

Secondary Endpoints

• Investigator-assessed progression-free survival, defined as time from randomization until disease progression or death from any cause

• Overall response rate • Incidence of adverse events

Key Inclusion Criteria

Key Exclusion Criteria

• Adult patients ≥18 years of age • Diagnosis of CLL per diagnostic criteria and relapsed or refractory CLL per the iwCLL guidelines • Previously treated with 1-3 lines of therapy (eg, completed ≥2 treatment cycles per therapy), including ≥1 standard chemotherapy-containing regimen • Previously treated with bendamustine, only if duration of response was ≥24 months • ECOG performance status of 0-1 • Adequate bone marrow function • Adequate renal and hepatic function

• Transformation of CLL to aggressive non-Hodgkin lymphoma or CNS involvement by CLL • Undergone an allogenic stem-cell transplant • A history of significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease • Hepatitis B, hepatitis C, or known HIV-positive • Receiving warfarin treatment • Received an anti-CLL monoclonal antibody within 8 weeks prior to the first dose of study drug • Received any anticancer or investigational therapy within 14 days prior to the first dose of study drug or has not recovered from previous therapy • Received CYP3A4 inhibitors (such as fluconazole, ketoconazole and clarithromycin) or inducers (such as rifampin, carbamezapine, phenytoin, St John’s Wort) within 7 days prior to the first dose of GDC-0199/ABT-199 • Prior GDC-0199/ABT-199 treatment

To learn more about this study, please visit www.ClinicalTrials.gov (NCT02005471, GO28667) or call the Trial Information Support Line at 1-888-662-6728.

GDC-0199/ABT-199 is being codeveloped by AbbVie and Genentech, a member of the Roche Group.

Reference: ClinicalTrials.gov, as of 5/2014. A2396579

Disaster Planning

Bringing the Future into the Present…Continued from the cover rupts your business. It threatens income streams, company data, jobs, personal safety, and patient care. Who do you think employees and patients will turn to in an emergency? You, the practice manager. You are the one who your team members expect to have a plan. If you have a good one, then you can help guide your company through a rough spot and get the organization back on its feet. Since you never know when a crisis may strike, the best time to prepare is now. It is our hope that this article will serve as a guide to inspire you to start writing your plan, or to update or continue to add to the plan you have already developed. The authors will guide you through content to consider and provide checklists and tools to make preparation easier. The article will also focus on the coordination and communication necessary among staff and associates. For a jumpstart to planning, it may also be helpful to visit www. open-central.net to download a free disaster plan checklist.

Getting Started In 2004, Florida endured 4 hurricanes in a single season, and in 2005, Hurricane Katrina resulted in the displacement of large numbers of hematology/oncology patients, as well as medical practices. A great deal of time and resources were needed to help patients locate hematology/oncology physicians for continuity of care. Some patients had treatments delayed, or did not receive their treatments at all. Unfortunately, this scenario has been repeated throughout numerous disaster events across the country since 2005. While we cannot control or predict the future, we can plan for it, and we are even required to do so by the Health Insurance Portability

and Accountability Act (HIPAA) of 1996. Few people would argue that disaster planning is a waste of time, or that it is not important for maintaining patient safety and continuity of care. It is clearly good business practice to have a plan in place to ensure the financial stability of a practice, even—and especially—in the event of a disaster.

While we cannot control or predict the future, we can plan for it, and we are even required to do so.

Although it is recognized as important, seen as a sound business practice, and even mandated by federal law, how many oncology practices make disaster planning a priority? It seems to be one of those tasks that gets pushed to the back burner in favor of more immediate, more pressing needs in the office: those with high visibility that confront us daily, those that cannot be set on a back burner. Unfortunately, when a disaster strikes and its fallout is suddenly confronting and challenging us, it is too late to come up with a viable plan to get through. The most effective plan is developed by a team so that it does not depend solely on 1 person. It will help to designate someone as the disaster plan coordinator to lead the team. Other members to consider are the office manager, information technology manager, human resources manager, and accounts payable/bookkeeper. The makeup of your team may vary depending on the size of your practice.

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Regardless of the titles assumed by those staff members, you will want to make sure that attention is given to the specific tasks discussed below. The disaster plan coordinator will lead the team. Determine that person’s responsibilities, including oversight, to ensure each of the other team members maintains his or her assignments. Better yet, determine responsibilities with the person to gain buy-in and ownership in developing the plan. Then assign a backup disaster plan coordinator so that not everything is lost if the coordinator becomes unavailable in the event of an emergency.

Before Disaster Hits Below is an outline to guide your planning. Do not let the 10 steps overwhelm you, as you do not need to do them all at once or in order. Pick and choose where to start, divide them among staff and do some simultaneously, or commit to a set number of hours you will work on the plan each week. Before you know it, you will be checking tasks off your list and feeling good about it. Ten steps to take before disaster strikes:

1 2

Collect and organize emergency supplies (Table).

Maintain hard copy and electronic lists of important contact information. Keep copies in a secure place offsite. Lists may include business contacts such as your bank, chemotherapy supplier, biohazard waste disposal agency, office supplier, certified public accountant, or attorney. Include the name of the contact person, alternate contact person, product/ service, telephone number, fax number, e-mail address. The list should also comprise staff, includContinued on page 10

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

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Disaster Planning

Bringing the Future into the Presentâ&#x20AC;ŚContinued from page 8 societies for recommendations on who to include).

Table Emergency Supplies Two flashlights

Extra batteries Masking tape First aid kit stocked with aspirin, Tylenol, bandages, scissors, tweezers, antiemetics, adhesive tape, cold compresses, antibiotic ointment, disinfectant, cleaning solutions, burn treatment aloe, gauze, wound closures, safety pins, rubber gloves, saline, mask and CPR mask, sun block Blood products Blankets and towels Extra clothing Portable radio Bottled water Food Can opener Extension cords Disinfectant agents Biohazard container or bag Emergency tools, including crowbar, handsaw, work gloves, goggles, axe, shovel, hard hats, duct tape, folding ladder for rescue operations, hammer, and pliers Summary contact list of all critical vendors and business entities, as discussed in the article Staff telephone list

ing name, job description, home address, home telephone number, cell phone number, alternate telephone number, e-mail address, alternate e-mail address, emergency contact person, evacuation zone, initial notification, and subsequent notification.

Video and/or photograph your offices, equipment, and furniture inventory. Update it annually, and prior to any anticipated disaster (those with a 24-hour warning or more). Maintain copies both onsite and offsite.

Back up computer files on a regular basis (ie, financial records, patient clinical records, patient

demographic information, business and staff contact information, insurance documents, and accounts payable records). Maintain them onsite and offsite.

Prepare a script for your office telephone â&#x20AC;&#x153;on holdâ&#x20AC;? message. This can be e-mailed or faxed to a vendor that can update the script for incoming phone calls as needed.

Establish a central phone number for patients to call, as well as an alternate phone number offsite.

Identify alternate physicians and hospitals for patient referral in the event of a disaster (ie, contact county, state, and national medical

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Determine availability and ability to administer vaccinations for diseases such as polio, tetanus, hepatitis B, and hepatitis C.

Train staff. Once you have a written plan, keep a copy of it in a specific place in your office, as well as an electronic copy that is accessible through your website. Then, most importantly, make the plan available to all staff members. Conduct training to ensure everyone knows their roles and responsibilities in the event of a disaster. If appropriate, create an organization chart to show the chain of command in the event of a disaster. Update it annually through orientations, training sessions, and/ or emergency drills. The executive director of the practice should review and document the training at least once a year to ensure the plan is current and updated as needed.

Enroll in the Oncology Patient Emergency Network (OPEN) to ensure continuity of patient care. These are 10 valuable steps to take to prepare for a potential disaster. Remember to involve staff in preparations and preparedness. Keeping team members informed will facilitate efforts should a disaster strike. The first in a 2-part series, this article has addressed the importance of disaster planning and how to work with staff members to begin developing a disaster plan. Watch for the final article in this series, which provides guidance on how to engage patients, with an emphasis on patients sharing responsibility for their care. It will also address what to do when a disaster is imminent and when a disaster strikes. l

*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 ÂŠ 2010, Millennium Pharmaceuticals, Inc. All rights reserved. Printed in USA

V-10-0196

11/10

ACA Exchange Implementation

Survey Reveals Drawbacks to…Continued from the cover with traditional insurance products to accomplish tasks such as verifying patient eligibility and obtaining information about patients’ provider networks to facilitate referrals. “Some of these things I think are growing pains,” said Allison Brennan, MPP, senior advocacy advisor, MGMA, Washington, DC. “This is the first year. It is a transition for practices and patients and the insurance industry. So, some of these are going to get better over time.” Ms Brennan and colleagues included the survey in an e-newsletter that they e-mailed to all 22,500 members of the MGMA. Although the response rate was only 3.2%, respondents hailed from all but 4 states and were from 42 specialties. Their practices included multispecialty practices with primary and specialty care (19.3%), orthopedic surgery practices (10%), family practices (8.3%), and obstetrics/gynecology practices (6.6%). Approximately three-quarters (75.1%) were independent medical practices, and the mean practice size was 55.7 full-time– equivalent physicians. These are roughly similar proportions to those from the more than 1000 physician practices that responded to a September 2013 survey by MGMA.2 The earlier survey was intended to determine how practice administrators viewed the impending start of patient purchase of ACA insurance exchange products. The April 2014 survey results indicate that 15.1% of respondents regard the ACA insurance exchanges as very unfavorable to their practices, and 44.3% view them as unfavorable. Approximately three-quarters (76.5%) of respondents said that their practices are participating with new health insurance plans under the ACA. The main reasons cited for participation are remain-

ing competitive in the local market, replacing current charity care when uninsured patients obtain coverage, and providing care to underserved patient populations. The top reason cited for nonparticipation was the financial liability represented by the 90-day grace period for ACA exchange enrollees. Among respondents whose practices are participating, 84.8% offer coverage through 5 or fewer plans. Only 19.9% of respondents, however, said that their practices had been excluded from a network in which they would like to have been included. Just 25.8% of respondents said that their practice’s patient numbers had increased under the ACA, and approximately one-tenth (10.8%) said that their patient numbers had fallen. Furthermore, approximately one-third of respondents reported that payment rates under the ACA exchanges were somewhat lower than or equal to average payment rates from all of their traditional commercial contracts, at 32% and 36.6%, respectively. Just less than half (41.8%) said that rates were equal to those from traditional commercial products offered by the same payers. The situation was somewhat better compared with traditional Medicare and Medicaid, with 30.1% and 46.4% of practices, respectively, reporting higher reimbursement with the new exchanges than with these government programs. When Ms Brennan and colleagues probed the practical aspects of the implementation, they found an abundance of pain for practices and patients. Approximately onethird (31.5%) of respondents said that it has been very or extremely difficult to distinguish between patients with ACA insurance coverage versus traditional commercial health insurance not related to ACA exchanges, whereas 56.1%

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found it slightly or moderately difficult. Only 12.4% said it was not at all difficult. Furthermore, 63.2% have found it more difficult to verify patient eligibility for coverage, 62.3% said it was more difficult to obtain cost-sharing information, and 58.6% have found obtaining information about the plan’s provider network to facilitate referrals to be more difficult than with traditional commercial coverage. Fully 40.9% of those who completed the survey said that their practices had been unable to treat some patients, because their practices were not included in those patients’ insurance exchange networks. In addition, 94.8% of respondents said that it was likely that patients have high deductibles with the new products compared with traditional commercial coverage. “We are consistently denied ‘out of network’ approvals for the very sick who truly need to continue their care with providers who have worked with the patient for years,” wrote a respondent; another indicated that “payer directories [of providers in the practices’ networks] are woefully inaccurate and impossible to rely on.” Ms Brennan said that she and her colleagues have heard these complaints from a number of providers, and that they represent significant problems for patients and physicians. However, she said that these difficulties, like most of the others associated with the early days of exchange network use, are being worked on and should improve over time. l

References

1. Medical Group Management Association. MGMA ACA exchange implementation survey report. May 2014. www.mgma.com/government-affairs/issues-over view/aca/aca-exchange-implementation-report/acasurveyreport_online_2?ext=.pdf. Accessed June 5, 2014. 2. Medical Group Management Association Legislative and Executive Advocacy Response Network (LEARN). ACA insurance exchange implementation, Sept. 2013. www.mgma.com/Libraries/ Assets/Government%20Affairs/Advocacy/LEARN/ ACA-Exchange-Implementation-LEARN.pdf. Accessed June 5, 2014.

Take a bite out of G-CSF acquisition costs* GRANIX is another option in short-acting G-CSF therapy TM

GRANIX™ is an option for hospitals and payers to consider when determining health system budgets » FDA approved through the rigorous BLA† process » Teva’s short-acting G-CSF was first introduced in Europe in 2008 and is available in 42 countries‡1 » GRANIX J Code: J 1446-Injection, tbo-filgrastim, 5 micrograms, effective January 1, 2014 †Biologics License Application. ‡As of February 2014. *Based on wholesale acquisition cost (WAC) of all short-acting G-CSF products as of November 11, 2013. WAC represents published catalogue or list prices and may not represent actual transactional prices. Please contact your supplier for actual prices.

Indication

» GRANIX is a leukocyte growth factor indicated for reduction in the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Important Safety Information » Splenic rupture: Splenic rupture, including fatal cases, can occur following the administration of human granulocyte colonystimulating factors (hG-CSFs). Discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture in patients who report upper abdominal or shoulder pain after receiving GRANIX. » Acute respiratory distress syndrome (ARDS): ARDS can occur in patients receiving hG-CSFs. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS. » Allergic reactions: Serious allergic reactions, including anaphylaxis, can occur in patients receiving hG-CSFs. Reactions can occur on initial exposure. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim. » Use in patients with sickle cell disease: Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving hG-CSFs. Consider the potential risks and benefits prior to the administration of GRANIX in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis. » Potential for tumor growth stimulatory effects on malignant cells: The granulocyte colony-stimulating factor (G-CSF) receptor, through which GRANIX acts, has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded. » Most common treatment-emergent adverse reaction: The most common treatment-emergent adverse reaction that occurred in patients treated with GRANIX at the recommended dose with an incidence of at least 1% or greater and two times more frequent than in the placebo group was bone pain. Please see brief summary of Full Prescribing Information on adjacent page. For more information, visit GRANIXhcp.com. Reference: 1. Data on file. Teva Pharmaceuticals: Filgrastim MA Approvals Worldwide. February 2014.

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

Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-US-approved filgrastim product). Leukocytosis In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies. 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving GRANIX has not been adequately determined. 7 DRUG INTERACTIONS No formal drug interaction studies between GRANIX and other drugs have been performed. Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies of GRANIX in pregnant women. In an embryofetal developmental study, treatment of pregnant rabbits with tbo-filgrastim resulted in adverse embryofetal findings, including increased spontaneous abortion and fetal malformations at a maternally toxic dose. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In the embryofetal developmental study, pregnant rabbits were administered subcutaneous doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day. Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day. This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC0-24) of approximately 50-90 times the exposures observed in patients treated with the clinical tbo-filgrastim dose of 5 mcg/kg/day. 8.3 Nursing Mothers It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GRANIX is administered to a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. 8.4 Pediatric Use The safety and effectiveness of GRANIX in pediatric patients have not been established. 8.5 Geriatric Use Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients were 65 years of age and older. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients. 8.6 Renal Impairment The safety and efficacy of GRANIX have not been studied in patients with moderate or severe renal impairment. No dose adjustment is recommended for patients with mild renal impairment. 8.7 Hepatic Impairment The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment. 10 OVERDOSAGE No case of overdose has been reported. ©2013 Cephalon, Inc., a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. GRANIX is a trademark of Teva Pharmaceutical Industries Ltd. Manufactured by: Distributed by: Sicor Biotech UAB Teva Pharmaceuticals USA, Inc. Vilnius, Lithuania North Wales, PA 19454 U.S. License No. 1803 Product of Israel GRX-40189 January 2014 This brief summary is based on TBO-003 GRANIX full Prescribing Information.

FDA Update

Ofatumumab Approved for Chronic Lymphocytic Leukemia

The US Food and Drug Administration approved ofatumumab (Arzerra Injection, GlaxoSmithKline) in combination with chlor ambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia, for whom fludarabine-based therapy is considered inappropriate. The approval was based on the results of a multicenter, randomized, open-label trial comparing ofatumu mab in combination with chlorambucil with chlorambucil alone. The 447 patients included in the study were deemed ineligible for fludarabine-based therapy because of advanced age or comorbidities. Overall, 72% of patients had ≥2 comorbidities, and 48% had a creatinine clearance of <70 mL/min. Infusion of intravenous ofatumu mab was administered as 300 mg in cycle 1 on day 1, followed by 1000 mg on day 8 (first arm), or 1000 mg administered on day 1 of all subsequent 28-day cycles (second arm). In both arms, chlorambucil was administered at a dose of 10 mg/m2 orally on days 1 to 7 every 28 days. Before each infusion of ofatumumab, patients received premedication with acetaminophen, an antihistamine, and a glucocorticoid. The primary end point of the trial was progression-free survival (PFS) as assessed by a blinded independent review committee. The median PFS was 22.4 months (95% confidence interval [CI], 19-25.2) in patients receiving ofatumumab plus chlorambucil compared with 13.1 months (95% CI, 10.6-13.8) in patients receiving chlorambucil alone (hazard ratio, 0.57; 95% CI, 0.45-0.72; P <.001). The most common adverse reactions (≥5%) reported with ofatumu mab plus chlorambucil were infusion reactions, neutropenia, asthenia, headache, leukopenia, herpes sim-

plex, lower respiratory tract infection, arthralgia, and upper abdominal pain. Overall, 67% of the patients who received ofatumu mab had ≥1 symptoms of infusion reaction. In addition, 10% of patients had a grade ≥3 infusion reaction. (April 17, 2014)

an OS improvement with the addition of ramucirumab. Common adverse events reported with ramucirumab in clinical trials include diarrhea and high blood pressure. The recommended dose of ramucirumab is 8 mg/kg every 2 weeks, administered over 60 minutes until disease progression or unacceptable toxicity. (April 21, 2014)

Ramucirumab First FDA-Approved Drug for Advanced Stomach Cancer after Chemotherapy

Palonosetron Receives New Indication for CINV Prevention in Pediatric Patients

The US Food and Drug Administration (FDA) approved ramucirumab (Cyramza; Eli Lilly) for the treatment of patients with advanced stomach cancer or gastroesophageal junction adenocarcinoma, which mostly affects older adults. Ramucirumab is an angiogenesis inhibitor that blocks the blood supply to tumors and is intended to be used in patients with unresectable cancer or with metastatic stomach cancer after receiving chemotherapy with a fluoropyrimidineor a platinum-containing agent. This is the first FDA-approved therapy for patients with stomach cancer who have already received chemotherapy. Ramucirumab was approved under the FDA’s priority review program, and was also granted an orphan drug status, because it is intended to treat rare conditions. The safety and efficacy of ramucirumab were demonstrated in a clinical trial of 355 patients with unresectable or metastatic stomach or gastroesophageal junction cancer. Patients were randomized to ramucirumab (66%) or to placebo (34%). The main end point was overall survival (OS). The median OS was 5.2 months with ramuciru mab compared with 3.8 months with placebo (P <.001). Ramucirumab also improved patients’ progression-free survival compared with placebo. A second trial comparing ramucirumab plus paclitaxel versus paclitaxel alone also showed

August 2014

Palonosetron HCl (Aloxi; Eisai) injection received a new US Food and Drug Administration (FDA) indication for the prevention of acute chemotherapy-induced nausea and vomiting (CINV) associated with initial or repeated courses of emetogenic chemotherapy in children aged 1 month to <17 years. This is the first FDA approval of a therapy for the prevention of acute CINV in patients aged 1 month to 6 months. The age of peak cancer incidence among children occurs within the first year of life, so this approval provides an important option to children, and especially infants, undergoing chemotherapy. The FDA approval was based on 1 randomized, double-blind, noninferiority pivotal trial comparing palonosetron with ondansetron in pediatric patients. The primary end point was complete response, which was achieved in 59.4% of patients using palonosetron compared with 58.6% of patients receiving ondansetron. The trial also showed that pediatric patients required a higher dose of palonosetron based on weight than that required by adults; however, the safety profile of the drug in pediatric patients was consistent with its safety profile in adults. Palonosetron HCl is already approved for the prevention of CINV in adults aged ≥17 years. (May 28, 2014) l

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Clinical Trial Tracker

New Clinical Trials Under Way

he following clinical trials are currently recruiting participants with myelodysplastic syndrome (MDS) for inclusion. Each trial description includes the NLM Identifier to use as reference with Clinical Trials.gov.

Alemtuzumab in Patients with MDS The goal of this phase 2, open-label clinical trial is to assess the safety and efficacy of alemtuzumab in patients with MDS. Alemtuzumab is a humanized immunoglobulin G1 monoclonal antibody that destroys specific types of lymphocytes by targeting the CD52 protein. Participants will receive a test dose of 1 mg of alemtuzumab intravenously. If the test dose is tolerated, then patients will receive 10-mg doses intravenously for a 10-day treatment cycle. Patients will receive blood transfusions as needed. After completion of the trial, patients are required to return for follow-up at 1 month, 3 months, 6 months, and annually for 5 years. To be eligible for participation, individuals must be aged 18 to 72 years, have a diagnosis of MDS, have anemia requiring blood transfusion, and should not be receiving other therapies for MDS (except filgrastim, erythropoietin, or other transfusion support) for at least 4 weeks. The primary outcome of this trial is complete or partial hematologic response measured at 3 months after the first dose of alemtuzumab and sustained on ≥2 serial measurements performed 1 month apart. Other outcome measures include transfusion independence for red blood cells and/or platelets, overall survival, life-threatening toxicity, and transformation-free survival. This trial is expected to enroll 78 patients

and will be conducted at the National Institutes of Health Clinical Center in Bethesda, MD. For more information, contact Barbara Weinstein, RN, at 301594-4180 or weinsbar@nhlbi.nih. gov, or Christopher S. Hourigan, MD, at 301-451-0257 or hourig ancs@mail.nih.gov. The NLM Identifier is NCT00217594.

Pracinostat with Azacitidine for Previously Untreated MDS The purpose of this phase 2, randomized, double-blind trial is to determine the safety and efficacy of pracinostat plus azacitidine compared with placebo plus azacitidine in patients with previously untreated MDS. Patients in the experimental treatment arm will receive 60 mg of pracinostat orally 3 times a week for 3 weeks followed by 1 week of rest. Patients in the comparator arm will receive placebo orally 3 times a week for 3 weeks followed by 1 week of rest. Patients in both arms will be also administered azacitidine 75 mg/m2 subcutaneously or intravenously for 7 days of each 28-day cycle; treatment cycles will repeat. The trial is expected to enroll 100 patients. The primary outcome is efficacy at 6 months measured by complete remission rate. Other outcome measures include overall response rate and overall survival, hematologic improvement, duration of response, progression-free survival, rate of leukemic transformation, and adverse event profile. Patients aged ≥18 years with histologic evidence of MDS, bone marrow aspiration and biopsies within 28 days of the first study treatment, no previous treatment with hypomethylating agents, and clinical indication for azacitidine are eligible to participate in the trial if other criteria are met. This trial will be conducted at sites throughout the

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United States. For more information, please contact Guillermo Garcia-Manero, MD, at 713-7922121, MD Anderson Cancer Center in Houston, TX. The NLM Identifier is NCT01873703.

Safety and Efficacy of INCB024360 in Patients with MDS In this phase 2, open-label, single-group trial, investigators are evaluating the safety and efficacy of INCB024360 in patients with MDS, and the long-term outcomes of MDS after therapy with INCB024360, an inhibitor of the enzyme indoleamine 2,3-dioxygenase, is discontinued. The trial is expected to recruit 40 patients, and participants will receive the study drug in 28-day cycles. The duration of the study comprises the treatment phase followed by a 24-month follow-up period. To be eligible to participate in this trial, patients must be aged ≥18 years with a confirmed diagnosis of MDS and should meet other inclusion and exclusion criteria. Trial investigators will assess the overall response rate from time on treatment through follow-up (approximately 36 months). Secondary outcome measures include time to acute myeloid leukemia progression, overall survival, and number of patients with serious adverse events. This trial will be conducted at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, FL. For more information, contact Lisa Nardelli at 813-7454731 or lisa.nardelli@moffitt.org. The NLM Identifier is NCT01822691.

Decitabine and Vorinostat Con ditioning for High-Risk MDS The purpose of this phase 2, open-label, single-group trial is to facilitate natural killer (NK)-cell survival and expansion by adminisContinued on page 18

WORLD CUTANEOUS MALIGNANCIES S CONGRESS

& ™

GLOBAL BIOMARKERS CONSORTIUM

™

Clinical Approaches to Targeted Technologi Technologies

™

CONFERENCE

THIRD ANNUAL October 29 - November 1, 2014 Marriott Marquis • San Francisco, California

CONFERENCE CHAIR World Cutaneous Malignancies Congress Sanjiv S. Agarwala, MD Professor of Medicine Temple University School of Medicine Chief, Medical Oncology & Hematology St. Luke’s Cancer Center Bethlehem, PA

CONFERENCE CO-CHAIR Global Biomarkers Consortium Jorge E. Cortes, MD

CONFERENCE CO-CHAIR Global Biomarkers Consortium Roy S. Herbst, MD, PhD

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

Ensign Professor of Medicine Professor of Pharmacology Chief of Medical Oncology Director, Thoracic Oncology Research Program Associate Director for Translational Research Yale Cancer Center New Haven, CT 2014WCMC/GBC_Asize_111113

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Clinical Trial Tracker

New Clinical Trials…Continued from page 16 tering decitabine and vorinostat to patients with high-risk MDS. After receiving 10 mg/m2 of intravenous decitabine daily on days 1 to 5, and 200 mg of vorinostat orally twice daily on days 6 to 15, patients will receive a single infusion of CD3enriched and CD19-enriched donor NK cells intravenously on day 17, and a short infusion of interleukin-2 administered subcutaneously 3 times a week for 3 doses beginning on day 17. A second cycle of treatment will be repeated 6 to 8 weeks following the cycle 1 start date. Primary outcome measure is the objective response rate after 2 courses of treatment. Secondary outcome measures include safety and tolerability, number of patients who become transfusion independent, NK-cell expansion, and overall survival. Patients aged 18 to 75 years with high-risk MDS, who have had ≤2 cycles of hypomethylating agents (ie, azacitidine or decitabine) without evidence of treatment failure are eligible to participate in this study if other criteria are met. This clinical trial is expected to enroll 46 patients and will be conducted at the University of Minnesota Masonic Cancer Institute in Minneapolis. For more information, contact Erica Warlick, MD, at 612-625-5467 or ewarlick@ umn.edu. The NLM Identifier is NCT01593670.

lowed by Vidaza, both dosed subcutaneously at 75 mg/m2 on day 1 of either cycle 1 or cycle 2 per randomization assignment. Patients in the second treatment arm will receive Vidaza followed by azacitidine, both dosed subcutaneously at 75 mg/m2 on day 1 of either cycle 1 or cycle 2 per randomization assignment. To be eligible to participate in this study, patients must be aged ≥18 years, diagnosed with MDS, and prescribed Vidaza, and should meet additional criteria. The primary outcome of this trial is the measurement of azacitidine in plasma samples to determine Cmax, AUC0-t, and AUC0-∞ at 13 time points from predose to 8 hours after dosing. The secondary outcomes are safety and tolerability, measured by the number of patients with adverse events. Trial locations in the United States include California and Florida. For more information regarding recruitment in California, contact Veena Charu, MD, at 714999-1465 or veenacharu@gmail. com; Misagh Karimi, MD, at 951898-2828 or misagh.karimi@uson cology.com; or Steven Hager, MD, at 559-326-1222 or shager@ccare. com. For more information regarding recruitment in Florida, contact Manjesh Lingamurthy, MD, at 954267-7700 or manjesh.lingamurthy@ holy-cross.com. The NLM Identifier is NCT01152346.

Bioequivalence of Azacitidine in Patients with MDS The goal of this phase 1, randomized, open-label trial is to determine the bioavailability of azacitidine injection compared with the bioavailability of Vidaza (azaci tidine) in patients with MDS. This clinical trial uses a crossover model and is expected to enroll 36 participants. Patients in the first treatment arm will receive azacitidine fol-

Eltrombopag in Patients with Low-to-Intermediate Risk MDS The purpose of this phase 2, open-label, single-group trial is to determine whether eltrombopag can improve platelet counts and whether it is safe in patients with MDS. Eltrombopag mimics the protein thrombopoietin, which stimulates platelet production, and has been associated with increasing platelet counts in patients with

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chronic idiopathic thrombocytopenic purpura. The trial is expected to enroll 30 patients. Participants will receive eltrombopag orally once daily for 90 days; they will be monitored weekly for platelet counts and every 4 weeks for other clinical evaluations. If platelet counts improve after 90 days, additional doses of eltrombopag will be added to the treatment regimen. Primary outcomes are an increase in the platelet count of 20,000/µL from baseline as well as toxicity profile at 3 months. Secondary outcomes include any changes in the platelet count, changes in platelet transfusion requirements, incidence of bleeding, and changes in serum thrombopoietin level. Patients aged ≥18 years with a confirmed diagnosis of MDS and platelet count of ≤30,000/µL are eligible to participate in the trial if other criteria are met. This trial is located at the National Institutes of Health Clinical Center in Bethesda, MD. For more information, contact Barbara Weinstein, RN, at 301594-4180 or weinsbar@nhlbi.nih. gov; or Danielle M. Townsley, MD, at 301-402-3477 or townsleydm@ nhlbi.nih.gov. The NLM Identifier is NCT00961064.

Efficacy and Safety of Oral Rigosertib in MDS In this phase 2, open-label, single-group trial, investigators are evaluating the safety of rigosertib and whether it is associated with a reduction in the number of blood transfusion units needed in patients with MDS that is classified as low, intermediate-1, or trisomy 8 intermediate-2, and who are transfusion-dependent. It is expected that 60 patients will be enrolled in this study. Participants will receive 560 mg of rigosertib orally twice daily over a 14-day treatment course.

Clinical Trial Tracker

The primary outcome of this trial is the number of red blood cell transfusion units during an 8-week time frame. Other outcome measures include adverse events, change in the number of bone marrow blasts, and complete blood counts. Patients aged ≥18 years with a confirmed diagnosis of MDS and transfusion dependency defined as ≥4 units of red blood cells within 8 weeks before baseline are eligible to participate if other criteria are met. Trial locations include Arizona, Georgia, Minnesota, New York, and South Carolina. For more information, contact François E. Wilhelm, MD, PhD, at 609-281-7086 or fwilhelm@onconova.us. The NLM Identifier is NCT01584531.

Treosulfan and Fludarabine Phosphate with or without Total Body Irradiation in Patients with MDS The goal of this phase 2, randomized, open-label trial is to assess the efficacy of treosulfan and fludarabine phosphate with or without total body irradiation (TBI) prior to donor stem-cell transplant in patients with MDS. Patients in the first experimental treatment arm will receive treosulfan intravenously for 2 hours at 4 to 6 days before transplant (day 0) and fludarabine phosphate intravenously for 30 minutes at 2 to 6 days before transplant (day 0). Patients in the second experimental treatment arm will receive treosulfan and fludarabine phosphate as in the first treatment arm, and will also undergo low-dose TBI on day 0. Patients in both treatment arms will undergo allogeneic stem-cell transplant or bone-marrow transplant on day 0. The primary outcome is pro gression-free survival at 6 months posttransplant. Other outcome measures include changes in gene-

expression profiles, relapse risk, incidence of relapse or progression, nonrelapse mortality, overall survival, and incidence of acute or chronic graft-versus-host disease. This trial is expected to enroll 80 patients. To qualify for participation, patients must have donors who meet specified requirements, must be aged ≥18 years with a diagnosis of MDS, and should meet other inclusion and exclusion criteria. This clinical trial will be conducted at the Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium in Seattle, WA. For more information about this study, contact Principal Investigator H. Joachim Deeg at 206-667-5985. The NLM Identifier is NCT01894477.

hypothyroidism, and disease progression. This trial will be conducted throughout the United States. For more information, contact Novartis Pharmaceuticals at 888-669-6682. The NLM Identifier is NCT00940602.

Investigational Drug PF-04449913 in Patients with Refractory or Relapsed MDS In this phase 2, open-label, single-arm trial, investigators are as sessing the safety and efficacy of a hedgehog inhibitor, PF-04449913, in patients with refractory or relapsed MDS. Patients in the experimental arm will receive 100 mg of PF-04449913 orally once daily in 4-week cycles for a total of 4 cycles, followed by an optional continuation phase. This study will be divided into 2 stages: 20 patients will be enrolled in the first stage, and if ≥2 patients respond in this stage, then 15 additional patients will be enrolled in the second stage. The primary outcome is the overall response rate during a 6-month time period. Other outcome measures include number of patients with overall survival, event-free survival, and serious adverse events, and the median time to transformation to acute myeloid leukemia. To qualify for trial participation, patients must be aged ≥18 years with a confirmed diagnosis of MDS that is refractory to previous therapy with hypomethylating agents (ie, azacitidine and/or decitabine); they must also meet other criteria. This trial is expected to enroll 35 patients and will be conducted at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, FL. For more information, contact Lisa Nardelli at 813-745-4731 or lisa.nardelli@ moffitt.org. The NLM Identifier is NCT01842646. l

Event-Free Survival with Iron Chelation Therapy in Patients with MDS The purpose of this phase 2, randomized, double-blind trial is to prospectively evaluate the efficacy and safety of iron chelation therapy with deferasirox compared with placebo in patients with MDS and transfusional iron overload. This trial is expected to recruit 210 participants. Patients in the experimental arm will receive deferasirox, which will be provided as 125-mg, 250-mg, and 500-mg tablets. Patients in the comparator arm will receive placebo tablets. Patients aged ≥18 years with low-risk to intermediate-1–risk MDS, weighing between 35 kg and 135 kg, and with a ferritin level of >1000 µg/L are eligible to participate if other criteria are met. The primary outcome is event-free survival assessed up to 5 years after study randomization. Several secondary outcome measures include hematologic improvement, overall survival, proportion of patients with

August 2014

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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

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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.

XtandiAccess.com

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 e Infection 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

Patient and Provider Access

The 90-Day Grace Period: What Providers Need to Know By Sydney Abbott, JD, Manager, Provider Economics and Public Policy, Association of Community Cancer Centers

mplementation of the Patient Pro tection and Af fordable Care Act (ACA) brings many changes to the healthcare system, including the establishment of health insurance ex changes and new re quirements for insurance coverage. Health insurance marketplaces move toward the goal of universal coverage by providing an option for patients to purchase health insurance outside of an employer-sponsored program. However, because all plans offered through an exchange must meet minimum health benefits and other insurance reform requirements, such as coverage for young adults and removing the cap on annual benefits, individual plan premiums are often more expensive than patients expect. This could lead—and in some cases, already has led—to missed premium payments. Of particular concern to providers is the time in which services are deemed covered in the event of lapsed premium payments. The ACA provision extends, to 90 days, the grace period patients have to become current on any past payments before their insurance coverage is terminated. Current laws on late and premium payments vary by state, but the ACA replaces all existing state laws with the 90-day rule. The rule applies to all consumers, in all states, who purchase subsidized coverage through the ACA health insurance marketplace. After the first premium payment is made, patients have 90 days to pay the next

premium. If the patient does not pay for 2 months, the insurer can hold all claims. At the end of the third month, if the patient still has not paid, the insurer may terminate the patient’s policy. The rule requires insurers to reimburse providers during the first 30 days of the 90-day grace period. However, if a consumer still fails to

If coverage is dropped for nonpayment, physicians must work directly with patients to collect payments for the balance incurred during days 31 to 90 of the grace period. make a payment after 90 days and his or her coverage is dropped, insurers will not be required to pay for claims incurred during the last 60 days of the grace period. If coverage is dropped for nonpayment, physicians must work directly with patients to collect payments for the balance incurred during days 31 to 90 of the grace period. The grace period issue only applies to individuals who receive tax subsidies to purchase insurance through the health insurance marketplace. It is important to know that information on whether patients receive subsidies will not be noted on their insurance cards. Claims during unpaid days 31 through 90 may be pended. If the enrollee never pays his or her share, the claim is not payable by the insurer.

ONCOLOGY PRACTICE MANAGEMENT

I August 2014

The Oversight and Investigations Subcommittee of the House Energy & Commerce Com mittee recently held a hearing to ask insurers about health insurance marketplace enrollment and premium payment by enrollees. Repre sentative Michael Burgess of Texas and other subcommittee members expressed concern over the 90-day grace period and the chilling effect it may have on provider participation in exchange plans. Insurance company executives testifying at the hearing assured the subcommittee that adequate systems are in place to give physicians the ability to determine patient payment and eligibility status. Industry representatives said call centers—and in some instances, online applications—are available for premium payment verification. However, premium status policies vary by company and leave a complex process for providers and staff to determine a patient’s status. By the conclusion of the hearing, the Oversight and Investigations Subcommittee re mained concerned that this information is not readily available to the healthcare providers, who could be left holding the bag for care that is not reimbursable. The Association of Community Cancer Centers (ACCC) reiterates the concerns expressed by the House Energy & Commerce Committee members and urges Congress and the administration to work together to require more easily accessible and realtime patient status data to be available to providers. ACCC has submitted a letter to the administration about this issue and continues to work with members of Congress. We will keep members posted on any developments on the 90-day grace period. l

Wealth Management

New IRA Rollover Rules Issued by the IRS By Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF

he Internal Revenue Service (IRS) recently issued an announcement clarifying individual retirement account (IRA) rollover rules. This change in the position stated in IRS Publication 590, Individual Retirement Ar rangements, may have an impact on you and how you manage your retirement accounts. As such, the IRS will be rewriting IRS Publication 590 to reflect this change. According to the announcement, it will not be effective before January 1, 2015.

IRS Reverses Long-Standing Position The Internal Revenue Code currently states that if you receive a distribution from an IRA, you cannot make a tax-free rollover into another IRA if you’ve already completed a tax-free rollover within the previous 12 months. Let’s first look at the definition of a rollover. A rollover is a transaction where the taxpayer takes constructive receipt of funds from an IRA (other than a SIMPLE IRA in the first 2 years of participation) and then has a maximum of 60 days to put the funds back into an IRA (the same or a different IRA) in order to avoid a taxable distribution. It is important to note that a rollover from an IRA can also be deposited into a qualified plan within the 60-day limit to avoid taxation. It is also important to point out that a rollover from a Roth IRA may generally be made only to another Roth IRA. Rollovers are different than a direct transfer, where the funds are transferred as a trustee-to-trustee transfer and are transferred directly between the custodians/trustees of the IRAs or employer-sponsored plans involved. The number of direct

transfers is unlimited in any particular time period. The long-standing position of the IRS, reflected in Publication 590 and proposed regulations, has been that this rule applies separately to each IRA you own. Publication 590 provides the following example: “You have two traditional IRAs, IRA-1 and IRA-2. You make a taxfree rollover of a distribution from IRA-1 into a new traditional IRA (IRA-3). You cannot, within 1 year of the distribution from IRA-1, make a tax-free rollover of any distribution from either IRA-1 or IRA-3 into another traditional IRA. However, the rollover from IRA-1 into IRA-3 does not prevent you from making a tax-free rollover from IRA-2 into any other traditional IRA. This is because you have not, within the last year, rolled over, tax free, any distribution from IRA-2 or made a tax-free rollover into IRA-2.” The change in the IRS position is that the 1-rollover-per-year rule is now going to apply on a taxpayer basis, rather than on an IRA basis. This follows a recent tax court decision case (Bobrow v Commissioner), where the court held that the 1rollover-per-year rule applies to all of a taxpayer’s IRAs in the aggregate, and not to each IRA separately.

over within 60 days. He made only 1 rollover from each IRA. Therefore, according to Publication 590 and the proposed regulations, this should not have been an issue. However, the IRS served Mr Bobrow with a tax deficiency notice, and the case went to tax court. The IRS argued to the court that Mr Bobrow violated the 1-rollover-per-year rule. The tax court agreed with the IRS, relying on its previous rulings, the language of the statute, and the legislative history. The court held that regardless of how many IRAs he or she maintains, a taxpayer may make only 1 nontaxable rollover within each 12-month period.

What This Means For the rest of this year, the old 1-rollover-per-year rule in IRS Publication 590 will apply to any IRA distributions you receive. So if you have a need to use 60-day rollovers to move funds between IRAs, you have only a limited time to do so without regard to the new Bobrow interpretation. Summary A rollover transaction should only be considered in limited circumstances where there is an actual need for the funds for a short period of time, and it is expected that the entire amount of funds distributed are to be repaid within 60 days. Otherwise, a direct transfer should be the transaction of choice. l

Bobrow v Commissioner In this case, Mr Bobrow (a tax attorney) did the following: • On April 14, 2008, he withdrew $65,064 from IRA-1. On June 10, 2008, he repaid the full amount into IRA-1 • On June 6, 2008, he withdrew $65,064 from IRA-2. On August 4, 2008, he repaid the full amount into IRA-2. Mr Bobrow completed each roll-

August 2014

Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF, is the founder of Physician Financial Services, a New York–based firm specializing in income protection and wealth accumulation strategies for physicians. He can be reached at 800-481-6447 or by e-mail to Lkeller@physicianfinancialservices.com with comments or questions.

www.OncPracticeManagement.com

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

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 Nurse Navigator Novant Health Derrick L. Davis 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.

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 (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 sponsored by bioTheranostics (non–CE-certified activity) 2:30 pm - 3:30 pm Session 7 sponsored by Onyx Pharmaceuticals (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

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 - Marisa C. Weiss, MD • Hematologic Malignancies Navigation and Survivorship - Peg Rummel, RN, MHA, OCN • Head, Neck, and Neurologic Cancers Navigation and Survivorship - Laura Kabrich, RN • 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_81214

Drug Coding Supplied by RJ Health Systems

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

Associated ICD-9-CM codes for the treatment of leukemia: The following fifth-digit subclassification is for use with category 202: 0 unspecified site, extranodal and solid organ sites 1 lymph nodes of head, face, and neck 2 intrathoracic lymph nodes 3 intra-abdominal lymph nodes 4 lymph nodes of axilla and upper limb 5 lymph nodes of inguinal region and lower limb 6 intrapelvic lymph nodes 7 spleen 8 lymph nodes of multiple sites 202.4 Leukemic reticuloendotheliosis Hairy-cell leukemia The following fifth-digit subclassification is for use with category 204-208: 0 without mention of having achieved remission >Failed remission< 1 in remission 2 in relapse 204 Lymphoid leukemia Includes: leukemia: lymphatic lymphoblastic lymphocytic lymphogenous 204.0 Acute Excludes: acute exacerbation of chronic lymphoid leukemia (204.1) 204.1 Chronic 204.2 Subacute 204.8 Other lymphoid leukemia Aleukemic leukemia: lymphatic

ONCOLOGY PRACTICE MANAGEMENT

I August 2014

Drug Coding

lymphocytic lymphoid 204.9 Unspecified lymphoid leukemia 205 Myeloid leukemia Includes: leukemia: granulocytic myeloblastic myelocytic myelogenous myelomonocytic myelosclerotic myelosis 205.0 Acute Acute promyelocytic leukemia Excludes: acute exacerbation of chronic myeloid leukemia (205.1) 205.1 Chronic Eosinophilic leukemia Neutrophilic leukemia 205.2 Subacute 205.3 Myeloid sarcoma Chloroma Granulocytic sarcoma 205.8 Other myeloid leukemia Aleukemic leukemia: granulocytic myelogenous myeloid Aleukemic myelosis 205.9 Unspecified myeloid leukemia 206 Monocytic leukemia Includes: leukemia: histiocytic monoblastic monocytoid 206.0 Acute Excludes: acute exacerbation of chronic monocytic leukemia (206.1) 206.1 Chronic 206.2 Subacute 206.8 Other monocytic leukemia Aleukemic: monocytic leukemia monocytoid leukemia 206.9 Unspecified monocytic leukemia 207 Other specified leukemia Excludes: leukemic reticuloendotheliosis (202.4) plasma cell leukemia (203.1) 207.0 Acute erythremia and erythroleukemia Acute erythremic myelosis Di Guglielmoâ&#x20AC;&#x2122;s disease Erythremic myelosis 207.1 Chronic erythremia Heilmeyer-SchĂśner disease

August 2014

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Drug Coding

207.2 Megakaryocytic leukemia Megakaryocytic myelosis Thrombocytic leukemia 207.8 Other specified leukemia Lymphosarcoma cell leukemia 208 Leukemia of unspecified cell type 208.0 Acute Acute leukemia NOS Stem cell leukemia Blast cell leukemia Excludes: acute exacerbation of chronic unspecified leukemia (208.1) 208.1 Chronic Chronic leukemia NOS 208.2 Subacute Subacute leukemia NOS 208.8 Other leukemia of unspecified cell type 208.9 Unspecified leukemia Leukemia NOS

FDA approved for leukemia

Compendia listed off-label uses for leukemia

CPT ® administration codes

Generic (brand) name

HCPCS code - code description

aldesleukin (Proleukin)

J9015 - Injection, aldesleukin, per single-use vial

√

96409

amifostine (Ethyol)

J0207 - Injection, amifostine, 500 mg

√

96374

arsenic trioxide (Trisenox)

J9017 - Injection, arsenic trioxide, 1 mg

√

96413, 96415

asparaginase Erwinia chrysanthemi (Erwinaze)

J9019 - Injection, asparaginase (Erwinaze), 1000 IU

√

96401

azacitidine (Vidaza)

J9025 - Injection, azacitidine, 1 mg

√

96401, 96409, 96413

Bacillus CalmetteGuerin (BCG Vaccine)

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

√

90471, 90472

Bacillus CalmetteGuerin (Tice BCG, TheraCys)

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

√

51720

Bacillus CalmetteGuerin (Tice BCG, TheraCys)

J9031 - BCG (intravesical), per installation

√

51720

bendamustine (Treanda) J9033 - Injection, bendamustine hydrochloride, 1 mg

√

96413

betamethasone acetate & sodium phosphate (Celestone Soluspan)

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

√

11900, 11901, 20600, 20605, 20610, 96372

bosutinib (Bosulif)

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

√

N/A

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Drug Coding

FDA approved for leukemia

Compendia listed off-label uses for leukemia

CPT ® administration codes

Generic (brand) name

HCPCS code - code description

bosutinib (Bosulif)

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

√

N/A

busulfan (Busulfex)

J0594 - Injection, busulfan, 1 mg

√

96415, 96416

busulfan (Myleran)

J8510 - Busulfan, oral, 2 mg

√

N/A

carboplatin (Paraplatin)

J9045 - Injection, carboplatin, 50 mg

chlorambucil (Leukeran)

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

√

96409, 96413, 96415

√

N/A

chlorambucil (Leukeran) S0172 - Chlorambucil, oral, 2 mg

√

N/A

cladribine (Leustatin)

J9065 - Injection, cladribine, per 1 mg

√

96413, 96415

clofarabine (Clolar)

J9027 - Injection, clofarabine, 1 mg

√

96413, 96415

cyclophosphamide (Cytoxan)

J9070 - Cyclophosphamide, 100 mg

√

96409, 96413, 96415

cyclophosphamide (Cytoxan)

J8530 - Cyclophosphamide, oral, 25 mg

√

N/A

Cytarabine (Cytosar-U)

J9100 - Injection, cytarabine, 100 mg

√

96409, 96413, 96415, 96450

dasatinib (Sprycel)

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

√

N/A

daunorubicin (Cerubidine)

J9150 - Injection, daunorubicin, 10 mg

√

96409, 96413

daunorubicin citrate liposome (DaunoXome)

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

√

96413

decitabine (Dacogen)

J0894 - Injection, decitabine, 1 mg

√

96413, 96415

dexamethasone (Decadron)

J8540 - Dexamethasone, oral, 0.25 mg

√

N/A

dexamethasone (eg, Decadron)

J1100 - Injection, dexamethasone sodium phosphate, 1 mg

√

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

doxorubicin (Adriamycin)

J9000 - Injection, doxorubicin hydrochloride, 10 mg

√

96409

epirubicin (Ellence)

J9178 - Injection, epirubicin hydrochloride, 2 mg

√

96409, 96413

etoposide (VePesid)

J8560 - Etoposide, oral, 50 mg

√

N/A

August 2014

www.OncPracticeManagement.com

Drug Coding

FDA approved for leukemia

Compendia listed off-label uses for leukemia

CPT ® administration codes

Generic (brand) name

HCPCS code - code description

etoposide (Toposar)

J9181 - Injection, etoposide, 10 mg

√

96413, 96415

filgrastim (Neupogen)

J1440 - Injection, filgrastim (G-CSF), 300 mcg

√

96365, 96366, 96369, 96370, 96372, 96374

filgrastim (Neupogen)

J1441 - Injection, filgrastim (G-CSF), 480 mcg

√

96365, 96366, 96369, 96370, 96372, 96374

fludarabine (Fludara)

J9185 - Injection, fludarabine phosphate, 50 mg

√

96413

hydrocortisone (Solu-Cortef)

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

√

96365, 96366, 96372, 96374

hydroxyurea (Hydrea)

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

√

N/A

hydroxyurea (Hydrea)

S0176 - Hydroxyurea, oral, 500 mg

√

N/A

ibrutinib (Imbruvica)

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

√

N/A

idarubicin (Idamycin)

J9211 - Injection, idarubicin hydrochloride, 5 mg

√

96409

ifosfamide (Ifex)

J9208 - Injection, ifosfamide, 1 gram

imatinib (Gleevec)

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

√

N/A

imatinib (Gleevec)

S0088 - Imatinib, 100 mg

√

N/A

interferon alfa-2b (Intron A)

J9214 - Injection, interferon, alfa2b, recombinant, 1 million units

√

96372, 96401

irinotecan (Camptosar)

J9206 - Injection, irinotecan, 20 mg

√

96413, 96415

mechlorethamine (Mustargen)

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

melphalan (Alkeran)

J8600 - Melphalan, oral, 2 mg

√

N/A

melphalan (Alkeran)

J9245 - Injection, melphalan hydrochloride, 50 mg

√

96409, 96413

mercaptopurine (Purinethol)

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

√

N/A

mercaptopurine (Purinethol)

S0108 - Mercaptopurine, oral, 50 mg

√

N/A

methotrexate

J8610 - Methotrexate, oral, 2.5 mg

√

N/A

ONCOLOGY PRACTICE MANAGEMENT

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√

96409

√

96413, 96415

Drug Coding

FDA approved for leukemia

Compendia listed off-label uses for leukemia

CPT ® administration codes

Generic (brand) name

HCPCS code - code description

methotrexate

J9250 - Methotrexate sodium, 5 mg

√

96372, 96374, 96401, 96409, 96450

methotrexate

J9260 - Methotrexate sodium, 50 mg

√

96372, 96374, 96401, 96409, 96450

methylprednisolone (Depo-Medrol)

J1020 - Injection, methylprednisolone acetate, 20 mg

√

11900, 11901, 20600, 20605, 20610, 96372

methylprednisolone (Depo-Medrol)

J1030 - Injection, methylprednisolone acetate, 40 mg

√

11900, 11901, 20600, 20605, 20610, 96372

methylprednisolone (Depo-Medrol)

J1040 - Injection, methylprednisolone acetate, 80 mg

√

11900, 11901, 20600, 20605, 20610, 96372

methylprednisolone (Medrol)

J7509 - Methylprednisolone, oral, per 4 mg

√

N/A

mitoxantrone (Novantrone)

J9293 - Injection, mitoxantrone hydrochloride, per 5 mg

√

96409, 96413

nelarabine (Arranon)

J9261 - Injection, nelarabine, 50 mg

√

96413, 96415

nilotinib (Tasigna)

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

√

N/A

obinutuzumab (Gazyva)

C9021 - Injection, obinutuzumab, 10 mg

√

96413, 96415

obinutuzumab (Gazyva)

*J9999 - Not otherwise classified, antineoplastic drugs

√

96413, 96415

ofatumumab (Arzerra)

J9302 - Injection, ofatumumab, 10 mg

√

96413, 96415

omacetaxine mepesuccinate (Synribo)

J9262 - Injection, omacetaxine mepesuccinate, 0.01 mg

√

96401

pegaspargase (Oncaspar)

J9266 - Injection, pegaspargase, per single-dose vial

√

96401, 96413, 96415

pentostatin (Nipent)

J9268 - Injection, pentostatin, per 10 mg

ponatinib (Iclusig)

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

√

N/A

ponatinib (Iclusig)

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

√

N/A

prednisolone (eg, Millipred)

J7510 - Prednisolone, oral, per 5 mg

√

N/A

prednisone (eg, Deltasone)

J7506 - Prednisone, oral, per 5 mg

√

N/A

rituximab (Rituxan)

J9310 - Injection, rituximab, 100 mg

√

96413, 96415

√

August 2014

96409, 96413

www.OncPracticeManagement.com

Drug Coding

Generic (brand) name

FDA approved for leukemia

HCPCS code - code description

sodium phosphate P 32 A9563 - Sodium phosphate P 32, therapeutic, per millicurie

Compendia listed off-label uses for leukemia

CPT ® administration codes 79101

√

temozolomide (Temodar)

J8700 - Temozolomide, oral, 5 mg

teniposide (Vumon)

Q2017 - Injection, teniposide, 50 mg

thiotepa (Thiotepa)

J9340 - Injection, thiotepa, 15 mg

√

51720, 96409

topotecan (Hycamtin)

J9351 - Injection, topotecan, 0.1 mg

√

96413

vinCRIStine (Vincasar PFS)

J9370 - Vincristine sulfate, 1 mg

√

96409

vinCRIStine liposome (Marqibo)

J9371 - Injection, vincristine sulfate liposome, 1 mg

√

96413

zidovudine (Retrovir)

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

zidovudine (Retrovir)

S0104 - Zidovudine, oral, 100 mg

√

N/A 96413, 96415

√

N/A

√

N/A

*When billing a nonclassified medication using a CMS 1500 claim form, you must include both the HCPCS code in Item 24D and the drug name, strength, and NDC (National Drug Code) in Item 19 or Item 24A (shaded area) in order to ensure appropriate reimbursement. Please note: Check with payer regarding correct placement of medication information. References • HCPCS Level II Expert 2014 • Current Procedural Terminology (CPT ®) 2014 • CPT 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 (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 & Medicaid Services)

This information was supplied by:

30 Cold Spring Road, Rocky Hill, CT 06067 T: (860) 563-1223 • F: (860) 563-1650 • www.RJHealthSystems.com

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RJ Health Systems The Creators of ReimbursementCodes.com

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

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Drug Update

Zykadia (Ceritinib) Approved for the Treatment of Patients with Crizotinib-Resistant ALK-Positive Non–Small-Cell Lung Cancer By Lisa A. Raedler, PhD, RPh, Medical Writer

ung cancer is one of the most frequently diagnosed cancers, as well as the leading cause of cancer-related mortality in the United States.1 According to the American Cancer Society, more than 159,000 Americans will die from lung cancer in 2014, representing approximately 27% of all cancer deaths.1 Non– small-cell lung cancer (NSCLC), the most common form of lung cancer, accounts for 85% to 90% of all cases.2 NSCLC comprises a number of histologies, including adenocarcinoma, squamous-cell carcinoma, nonsquamous carcinoma, large-cell carcinoma, sarcomatoid carcinoma, and adenosquamous carcinoma.2 A recent analysis of claims data from an oncology registry associated with a large US commercial health plan has demonstrated the substantial cost burden associated with NSCLC.3 This study, which was published in 2013, assessed the total cost of treatment for more than 300 patients with advanced NSCLC who were continually enrolled in the plan from diagnosis until death.3 The average total healthcare costs ranged from approximately $19,000 to $167,000 for first-line NSCLC management, and from approximately $35,000 to $135,000 for second-line management.3 In this analysis, systemic therapy represented 20% to 55% of first-line total costs, and 22% to 68% of second-line total costs.3 Traditionally, patients with metastatic NSCLC have been managed with combinations of cytotoxic agents. Although the use of platinum-based doublets has improved the median overall survival for patients with advanced NSCLC from 4 to 5 months to 8 to 10 months (in treat-

ment-naïve patients), these chemotherapy combinations are limited by significant toxicities, including myelosuppression, nausea and vomiting, and severe fatigue.4-6 As knowledge of tumor-cell biology in lung cancer evolves, small molecules that target specific genetic mutations offer the opportunity to manage patients with NSCLC using a personalized approach.6 In NSCLC, multiple driver oncogenes have been identified, including EGFR, ALK, and KRAS.6 Among North American patients with advanced NSCLC, approximately 10% express mutations in EGFR,7 approximately 23% express mutations in KRAS,8 and up to 13% express activating mutations or translocations of ALK.9 Identifying EGFR and ALK mu tations can help to decide whether a given patient with NSCLC can benefit from today’s targeted therapies, including erlotinib and afatinib (EGFR inhibitors) or crizotinib (an ALK inhibitor). Granted an accelerated approval by the US Food and Drug Administration (FDA) in 2011, crizotinib was the first treatment available for patients with metastatic NSCLC whose tumors are ALK-positive.10 An open-label, active-controlled, multinational, randomized clinical trial demonstrated prolonged progression-free survival with crizotinib compared with chemotherapy in ALK-positive, metastatic NSCLC. Vision disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue were the most common adverse reactions observed among recipients of crizotinib in this trial.10 To overcome the documented resistance to crizotinib, researchers contin-

ONCOLOGY PRACTICE MANAGEMENT

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ue to investigate medications that target ALK mutations.6 Novel kinase inhibitors currently being investigated in clinical trials for patients with ALK mutation NSCLC include alectinib, ganetespib, and AP26113.6,11

Ceritinib: New Treatment Option for ALK-Positive NSCLC On April 29, 2014, the FDA approved ceritinib (Zykadia; Novartis Pharmaceuticals), a kinase inhibitor, for the treatment of patients with metastatic ALK-positive NSCLC who are intolerant of, or whose disease progressed during therapy with, crizotinib.12 This approval was granted under the FDA’s accelerated process based on unpublished clinical trial data demonstrating significant tumor response rate and duration of response.12 Improvements in survival or disease-related symptoms have not been demonstrated.13 The approval of ceritinib was based on the results of a multicenter, single-arm, open-label clinical trial that enrolled 163 patients with ALK-positive metastatic NSCLC that had progressed with crizotinib or who were intolerant of that drug.12,13 Ceritinib was administered at a dose of 750 mg once daily.12,13 “Zykadia represents an important treatment option for ALK-positive NSCLC patients who relapse after starting initial therapy with crizotinib,” noted lead investigator Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston.14 “This approval will affect the way we manage and monitor patients with this type of lung cancer, as we will now be able to offer them the opportunity for continued treatment response with a new ALK inhibitor.”14

Drug Update

Mechanism of Action In vitro and in vivo assays demonstrate that ceritinib, a kinase inhibitor, hinders the proliferation of ALK-dependent cancer cells by blocking the autophosphorylation of ALK, as well as ALK-mediated phosphorylation of STAT3, a downstream signaling protein. Ceritinib also targets insulin-like growth factor 1 receptor, insulin receptor, and ROS1.13 Dosing and Administration Ceritinib should be administered at a dose of 750 mg orally once daily until disease progression or until unacceptable toxicity. It should be taken on an empty stomach, but not within 2 hours of a meal. If a dose of ceritinib is missed, it should be administered only if the next dose is not due within 12 hours.13 Single-Arm Phase 2 Trial The multicenter, single-arm, openlabel trial of ceritinib enrolled 163 patients with the ALK-mutation NSCLC whose disease progressed while receiving crizotinib or those who were intolerant of crizotinib.13 Objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.0 was the primary end point of this study. This parameter was evaluated by the investigators and by a central Blinded Independent Review Committee.13 Patient Population In the phase 2 ceritinib trial, most patients with ALK-positive NSCLC were female (54%), Caucasian (66%), aged <65 years (87%), and never or former smokers (97%).13 The majority (87%) had an Eastern Cooperative Oncology Group performance status of 0 or 1.13 Overall, 91% of patients had progressed with previous treatment of crizotinib, 84% had received ≥2 previous therapies, and 93% had adenocarcinoma histology.13 Common sites of extrathoracic metastases

Table 1 Response Rate and Duration of Response with Crizotinib in Patients with ALK-Positive NSCLC Investigator assessment (N = 163)

BIRC assessment (N = 163)

54.6 (95% CI, 47-62)

43.6 (95% CI, 36-52)

Complete response, %

1.2

2.5

Partial response, %

53.4

41.1

7.4 (95% CI, 5.4-10.1)

7.1 (95% CI, 5.6-not estimable)

Efficacy end point Overall response rate, %

Duration of response, median, months

BIRC indicates Blinded Independent Review Committee; CI, confidence interval. Source: Zykadia (ceritinib) capsules prescribing information; April 2014.

included the brain (60%), liver (42%), and bone (42%).13 Retrospective verification of ALK positivity was performed by review of local test results for 99% of patients.13

rhea (16%), and vomiting (16%).13 Serious adverse drug reactions that were reported in ≥2% of patients receiving ceritinib included convulsion, pneumonia, interstitial lung disease/pneumonitis, dyspnea, dehydration, hyperglycemia, and nausea.13 Of the patients receiving ceritinib, 5% had fatal adverse reactions, including pneumonia, respiratory failure, interstitial lung disease/pneumonitis, pneumothorax, gastric hemorrhage, general physical health deterioration, pulmonary tuberculosis, cardiac tamponade, and 1 case of sepsis.13 Overall, 10% of patients receiving ceritinib discontinued therapy as a result of adverse reactions.13 Pneumonia, interstitial lung disease/pneumonitis, and decreased appetite were the most common adverse drug reactions that led to discontinuation in ≥1% of patients.13 Of note, ceritinib should be discontinued in patients who do not tolerate 300 mg daily dosing.13 Table 2 lists the common adverse reactions and Table 3 lists the laboratory abnormalities reported in patients treated with ceritinib.13 Additional adverse reactions occurring in ≥2% of the patients receiving ceritinib include neuropathy (17%), manifested as paresthesia, muscular weakness, gait disturbance, peripheral neuropathy, hypoesthesia, peripheral sensory neuropathy, dysesthesia, neuralgia, peripheral motor neuropathy, hypotonia, or polyneu-

Efficacy The phase 2 study demonstrated that ceritinib is active in patients with ALK-positive NSCLC, with an ORR of 54.6% by investigator assessment and a median duration of response of 7.4 months. All participants received ceritinib at an initial dose of 750 mg daily. The median duration of exposure to ceritinib was 6 months.13 The findings of the Blinded Independent Review Committee were similar to those of the investigators. Table 1 lists the findings on ORR and duration of response from this study.13 Safety and Adverse Events The safety of ceritinib was established based on data from 255 patients with ALK-positive disease in the phase 2 study—246 patients with NSCLC and 9 patients with other cancer types.13 A total of 59% of the patients receiving ceritinib required dose reductions as a result of adverse reactions.13 The adverse reactions that led to dose reductions or interruptions were reported in ≥10% of patients and included increased alanine aminotransferase (ALT; 29%), nausea (20%), increased aspartate aminotransferase (AST; 16%), diar-

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Drug Update

Zykadia (Ceritinib) Approved for…Continued from page 37 Table 2 Adverse Reactions Reported with Ceritinib in >10% of Patients for All Grades or ≥2% for Grades 3/4 Ceritinib (N = 255) Adverse reaction

All grades, %

Grade 3/4, %

Diarrhea

Nausea

Vomiting

Abdominal pain/discomfort, epigastric discomfort

Constipation

Esophageal disorder: dyspepsia, gastroesophageal reflux disease, dysphagia

Fatigue/asthenia

Decreased appetite

Rash, maculopapular rash, acneiform dermatitis

Gastrointestinal events

Other events

Source: Zykadia (ceritinib) capsules prescribing information; April 2014.

Table 3 Key Laboratory Abnormalities in >10% (All Grades) of Patients Receiving Ceritinib Ceritinib (N = 255) Laboratory abnormality

All grades, %

Grade 3/4, %

Hemoglobin decreased

Alanine transaminase increased

Aspartate transaminase increased

Creatinine increased

Glucose increased

Phosphate decreased

Lipase increased

Bilirubin (total) increased

Source: Zykadia (ceritinib) capsules prescribing information; April 2014.

ropathy; vision disorder (9%), including vision impairment, blurred vision, photopsia, accommodation disorder, presbyopia, or reduced visual acuity; prolonged QT interval (4%); and bradycardia (3%).13

Warnings and Precautions Severe/persistent gastrointestinal toxicity. Of the 255 patients receiving ceritinib in the phase 2 study, 96% had diarrhea, nausea, vomiting, or abdominal pain; severe cases were reported in 14% of the patients.

Dose modification was required in 38% of patients as a result of diarrhea, nausea, vomiting, or abdominal pain. Patients should be managed using standards of care, as needed. Based on the severity of the adverse drug reaction, ceritinib should be withheld and then resumed with a 150-mg dose reduction.13 Hepatotoxicity. Of the 255 patients in the phase 2 study, 27% had elevations in ALT that were greater than 5 times the upper limit of normal. Permanent discontinuation resulting

ONCOLOGY PRACTICE MANAGEMENT

I August 2014

from elevated transaminases and jaundice was required in 1 (0.4%) patient. Patients should undergo laboratory tests, including ALT, AST, and total bilirubin, once monthly and as clinically indicated. More frequent testing is warranted in patients who develop transaminase elevations. Ceritinib should be withheld, dose reduced, or should be permanently discontinued based on the severity of the hepatotoxicity reaction.13 Interstitial lung disease/pneumonitis. Severe, life-threatening, or fatal interstitial lung disease/pneumonitis has occurred in patients receiving ceritinib. Pneumonitis was reported in 4% of the 255 patients in the phase 2 study. In all, 3% of patients had grade 3 or 4 disease, and 1 patient died. Ceritinib was discontinued in 1% of patients because of interstitial lung disease/pneumonitis. If symptoms indicative of interstitial lung disease/ pneumonitis are observed, exclude other potential causes. If interstitial lung disease/pneumonitis is deemed to be treatment-related, discontinue ce ritinib therapy permanently.13 QT interval prolongation. In the phase 2 study and across the development program of ceritinib, 3% of patients had corrected QT (QTc) interval increase from a baseline of >60 msec.13 Across the development program of ceritinib, 1 patient using doses ranging from 50 mg to 750 mg had a QTc of >500 msec.13 Ceritinib should be avoided in patients with congenital long QT syndrome. Patients with congestive heart failure, bradyarrhythmias, or electrolyte abnormalities, and those taking medications known to prolong the QTc interval should undergo periodic electrocardiograms (ECGs) and electrolyte monitoring.13 Ceritinib should be withheld in patients who develop a QTc interval of >500 msec on at least 2 separate ECGs. Ceritinib can be resumed with a 150-mg dose reduction if the

Drug Update

QTc interval is <481 msec or on recovery to baseline if the QTc interval is ≥481 msec.13 Ceritinib should be permanently discontinued in patients who develop QTc interval prolongation in combination with torsades de pointes, polymorphic ventricular tachycardia, or signs or symptoms of serious arrhythmia.13 Hyperglycemia. Grade 3 or 4 hyperglycemia based on laboratory values occurred in 13% of patients in the phase 2 study of ceritinib. The risk for grade 3 or 4 hyperglycemia in patients with diabetes or glucose intolerance was increased 6-fold. There was a 2-fold increase in the risk for grade 3 or 4 hyperglycemia in patients taking corticosteroids. Serum glucose levels should be monitored, and antihyperglycemic medications should be used as indicated. Ceritinib should be withheld until hyperglycemia is controlled and then resumed with a 150mg dose reduction. If adequate hyperglycemic control cannot be achieved, ceritinib should be discontinued.13 Bradycardia. Sinus bradycardia was observed as a new finding in 1% of patients and was reported as an adverse drug reaction in 3% of patients in the phase 2 study of ceritinib.13 Ceritinib should be avoided in patients taking other agents known to cause bradycardia (eg, beta-blockers, nondihydropyridine calcium channel blockers, clonidine, and digoxin) if possible. Heart rate and blood pressure should be monitored regularly.13 If symptomatic bradycardia is not life-threatening, ceritinib should be withheld until recovery or until the heart rate is ≥60 beats per minute (bpm). Concomitant medication use should be evaluated, and ceritinib dose should be adjusted. If bradycardia is associated with a medication known to cause bradycardia or hypotension, ceritinib can be withheld until recovery or to a heart rate of ≥60 bpm. If the concomitant medication can be adjusted or discontinued, ceritinib can be restarted at a

150-mg dose reduction on recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, with frequent monitoring. Ceritinib should be discontinued if life-threatening bradycardia is observed and no concomitant medication use is identified.13 Embryofetal toxicity. Based on its mechanism of action, ceritinib may cause fetal harm when administered to a pregnant woman.

the second oral kinase inhibitor approved for the initial treatment of ALK-positive metastatic NSCLC, has demonstrated efficacy with manageable side effects. Ceritinib joins crizotinib as the second FDA-approved agent for this subset of patients with NSCLC, offering an effective alternative to cytotoxic therapy. Ceritinib may confer clinical value in other cancers in which ALK mutations are present. In addition to further exploration in NSCLC, clinical studies are evaluating ceritinib in pediatric malignancies and other tumors characterized by genetic abnormalities of ALK.15 l

Specific Populations Pregnancy. Ceritinib is in Pregnancy Category D. Women of reproductive potential should be made aware of the potential hazard to a fetus, as well as the need to use effective contraception during treatment with ceritinib and for at least 2 weeks after the completion of therapy.13 Nursing mothers. Whether ceritinib or its metabolites are excreted in human milk is not known. Nursing mothers who take ceritinib should discontinue breastfeeding.13 Pediatric use. The safety and effectiveness of ceritinib have not been established in pediatric patients.13 Geriatric use. Clinical studies of ceritinib did not include sufficient numbers of patients aged ≥65 years to assess its effect on older patients. Of the 255 patients in the phase 2 study, 40 (16%) were aged ≥65 years.13 Hepatic impairment. Because ceritinib is eliminated primarily in the liver, patients with hepatic impairment may have increased exposure. Based on a pharmacokinetic analysis, dose adjustment is not recommended for patients with mild hepatic impairment. A recommended dose has not been determined for patients with moderate-to-severe hepatic impairment.13

References

1. American Cancer Society. What are the key statistics about lung cancer? Revised April 30, 2014. www.cancer.org/ cancer/lungcancer-non-smallcell/detailedguide/non-smallcell-lung-cancer-key-statistics. Accessed May 15, 2014. 2. American Cancer Society. What is non-small cell lung cancer? Revised April 30, 2014. www.cancer.org/cancer/lungcan cer-non-smallcell/detailedguide/non-small-cell-lung-cancerwhat-is-non-small-cell-lung-cancer. Accessed May 15, 2014. 3. Henk HJ, Ray S. Treatment patterns and healthcare costs among patients with advanced non-small-cell lung cancer. Lung Cancer Manag. 2013;2:189-197. 4. Azzoli CG, Giaccone G, Temin S. American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer. J Oncol Pract. 2010;6:39-43. 5. American Cancer Society. Chemotherapy for non-small cell lung cancer. Revised April 30, 2014. www.cancer.org/can cer/lungcancer-non-smallcell/detailedguide/non-small-celllung-cancer-treating-chemotherapy. Accessed May 15, 2014. 6. Villaflor VM, Salgia R. Targeted agents in non-small cell lung cancer therapy: What is there on the horizon? J Carcinog. 2013;12:7. 7. Hirsh V, Melosky B, Goss G, et al. A personalized approach to treatment: use of EGFR tyrosine kinase inhibitors for the treatment of non-small-cell lung cancer in Canada. Curr Oncol. 2012;19:78-90. Erratum in: Curr Oncol. 2012;19:e228. 8. Massarelli E, Varella-Garcia M, Tang X, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non–small-cell lung cancer. Clin Cancer Res. 2007;13:2890-2896. 9. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non–small-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009;27:4247-4253. 10. US Food and Drug Administration. Drugs: crizotinib. www.fda.gov/drugs/informationondrugs/approveddrugs/ ucm376058.htm. Accessed May 17, 2014. 11. Iwama E, Okamoto I, Harada T, et al. Development of anaplastic lymphoma kinase (ALK) inhibitors and molecular diagnosis in ALK rearrangement-positive lung cancer. Onco Targets Ther. 2014;7:375-385. 12. US Food and Drug Administration. FDA approves Zykadia for late-stage lung cancer: breakthrough therapy drug approved four months ahead of review completion goal date. Press release. April 29, 2014. www.fda.gov/news events/newsroom/pressannouncements/ucm395299.htm. Accessed July 24, 2014. 13. Zykadia (ceritinib) capsules [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; April 2014. 14. Novartis. Novartis gains FDA approval for Zykadia(TM), first therapy for patients with ALK+ NSCLC previously treated with the ALK inhibitor crizotinib. April 29, 2014. www.novartis.com/newsroom/media-releases/en/ 2014/1776962.shtml. Accessed May 17, 2014. 15. ClinicalTrials.gov. LDK378. Search results. http://clin icaltrials.gov/ct2/results?term=LDK378&Search=Search. Accessed May 17, 2014.

Conclusion NSCLC remains the main cause of death from cancer in the United States for men and women. The disease is still diagnosed mainly at advanced stages; therefore, prognosis is poor, and long-term survival is rare. Ceritinib,

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