Oncology Practice Management December 2013

www.OncPracticeManagement.com

DECEMBER 2013

VOLUME 3 • NUMBER 8

Oncology Practice Management ™

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

From the Editor

Tension at the Top Leaving 2013 Behind

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

I

n the group practice setting, I have seen many of my practice manager friends and colleagues retire, change jobs, or—worse yet— be relieved of their management position. What is going on lately?

External pressures from the outside and internal pressures from inside the practice are making for an environment like quicksand for practice managers and owner-physicians. Some of these external pressures are caused by the Centers for Medicare & Medicaid Service (CMS)’s continued reductions, which often influence commercial contracts.

We face great uncertainty with the workings of the Affordable Care Act as it is currently being presented to us. Regulations and threatened

By Dawn Holcombe, MBA, FACMPE, ACHE

T

he management of oncology practices has always been complicated. Under the best of circumstances, managing the expectations of patients, staff, and owner-physicians is difficult. If you are lucky, you have been blessed with a strong team and a well-oiled machine. In addition, well-prepared practices have physician leaders and administration who value the strengths that each brings to the

guidance and direction of the practice.

The reality is that there are so many elements coming to bear on oncology care delivery that are not under the control of the leadership team. As Ruth Linné Lander comments in her article, “Tension at the Top,” this is where the rubber hits the road—and the road got very bumpy in 2013.

The changes we saw this year are not Continued on page 8

Exclusive Provider Organizations: Will Physicians Be Seduced?

By Mary Pat Whaley, FACMPE, CPC Physician Advocate and Consultant, Manage My Practice

P

hysicians, meet another version of the alphabet insurance plan that is structured to reimburse you even less for your services. (In my mind, I see physicians all over America standing up

and doing the Howard Beale thing from the movie “Network.”)

What Is an EPO? An exclusive provider organization Continued on page 17

Continued on page 12 From the publishers of

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INTEGRATING ONCOLOGISTS, PAYERS, AND THE ENTIRE CANCER CARE TEAM

of n it o s D ia er VI ssoc ent own g O A r C td in PR y the nce Shu ang a t R D N ou bity C en ng- 55 A y m o T t to mun ern ve L ts…

N v c h m o a TIE roug Co e G y H Effe a A B

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Table of Contents

December 2013 • Volume 3 • Number 8

PUBLISHING STAFF Senior Vice President/Group Publisher Nicholas Englezos nenglezos@the-lynx-group.com Vice President/Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Publisher Cristopher Pires cpires@the-lynx-group.com Director, Client Services Lou Lesperance llesperance@the-lynx-group.com Editorial Director Dalia Buffery dbuffery@the-lynx-group.com Managing Editor Lisa Neuman lneuman@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 Director, Human Resources Blanche Marchitto Associate Director, Content Strategy & Development John Welz Associate Editorial Director, Projects Division Terri Moore 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 Managers Andrea Boylston Jini Gopalaswamy Project Coordinators Jackie Luma Deanna Martinez IT Specialist Carlton Hurdle Executive Administrator Rachael Baranoski Office Coordinator Robert Sorensen Engage Healthcare Communications 1249 South River Road - Ste 202A Cranbury, NJ 08512 phone: 732-992-1880 fax: 732-992-1881

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Oncology Practice Management ™

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

FEATURES From the Editor Leaving 2013 Behind...............................................................................................1

By Dawn Holcombe, MBA, FACMPE, ACHE

Manager-Physician Communication Tension at the Top..................................................................................................1

By Ruth Linné Lander, FACMPE

Best Practices Exclusive Provider Organizations: Will Physicians Be Seduced?….......................1

By Mary Pat Whaley, FACMPE, CPC

Physicians Push to Increase Awareness of Cancer Overdiagnosis and Overtreatment…..........................................................................................18

By Rosemary Frei, MSc

340B Drug Pricing Program Shift to Hospital-Based Oncology Inadvertently Spurred by the 340B Drug Pricing Program….............................................................................25

By Rosemary Frei, MSc

IOM Call to Action Institute of Medicine Recommends Measures to Achieve High-Quality Cancer Care…...............................................................................29

By Rosemary Frei, MSc

Continued on page 6

MISSION STATEMENT Oncology healthcare requires providers to focus attention on financial concerns and strategic decisions that affect the bottom line. To continue to provide the high-quality care cancer patients deserve, providers must master the ever-changing business of oncology. Oncology Practice Management will offer 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.

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

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Table of Contents

December 2013 • Volume 3 • Number 8

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 ©2013 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

DEPARTMENTS Wealth Management Checklist to Cut Your 2013 Taxes........................................................................37

By Andrew D. Schwartz, CPA; and Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF

Drug Coding FDA-Approved Medications Used for the Treatment of Lymphoma.....................................................................................42 Clinical Trial Tracker Clinical Trials Underway for Pediatric, Adolescent, and Young Adult Patients with Cancer…...........................................................51 Patient and Provider Access The Government Shutdown May Have Long-Ranging Effects…........................................................................................55

By Sydney Abbott, JD

EDITORIAL ADVISORY BOARD Editor-in-Chief Dawn Holcombe, MBA, FACMPE, ACHE President DGH Consulting South Windsor, CT

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 CEO Lancaster Cancer Center Ltd. Lancaster, PA

Peggy Barton, RN Practice Manager Toledo, OH

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

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

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

Carla C. Wood Balch, CPC, MS President Altos Solutions, Inc Los Altos, CA

Risë Marie Cleland President Oplinc, Inc Portland, OR Craig K. Deligdish, MD Hematologist/Oncologist Oncology Resource Networks Orlando, FL

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Marianna Lamb, MS Exceutive Director Medical Oncology Association of Southern California Upland, CA

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

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From the Editor

Leaving 2013 Behind Continued from page 1 going to slow. In fact, they are likely to escalate even more quickly over at least the next 5 years as we transition from a predominantly fee-for-service model in­ to some form of performance or “value”-based Dawn Holcombe, model. Programs in pilot MBA, FACMPE, ACHE versions now across the country will provide direction, but none of these are likely to emerge as the “one” solution.

Despite the proliferation of “quality” metrics and programs that have emerged in the last 5 years, we see in the article, “Institute of Medicine Recommends Measures to Achieve High-Quality Cancer Care” (page 29) that the Institute of Medicine (IOM) has found that we are in a crisis of quality as a specialty—with little progress to report since the IOM’s last review of cancer quality in 1999. How can this be? Some would blame the lack of financial support; others the fragmentation that continues to plague the healthcare delivery system. Still others would point to lags in technology, or the inconsistency of documentation and its monitoring and tracking. It is undeniably true that each practice or cancer center in the country seems to have built their own platform (even those who use the same vendor as a group down the street). Is it no wonder, then, that the patients with cancer who pay for the care we provide lament the lack of information and definition of “value-based” care?

Dozens of conferences in 2013 addressed quality, value, evidence, and reform in oncology. They were presented from the perspective of the community, the integrated centers, the payers, specialty pharmacies, employers, and leading cancer-based organizations. We are

8

I

making progress, but clearly we are still all describing different parts of the same elephant, and haven’t yet figured out how to combine these diverse perspectives into a singular vision.

One common issue that has been raised in all of these discussions is the exchange of financial resources—a “cost” or “reimburse-

Good oncology practices, both private and hospital-based, will become meticulous about resource management. We, out of necessity, will turn the delivery models upside down.

ment,” depending upon your own perspective. As I move between the payer and provider worlds, I still hear all too often a palpable disconnect between the expectations for what level of financial resources is appropriate, and how those resources will be allocated.

How do we reconcile the disconnect between the expectations for better pay for performance, quality, and value, and the concurrent expectations for finding savings in the clearly unsustainable costs for healthcare in the United States?

The simple answer is that we are not going to reconcile those disparate views. There is no more money, and discussions of shared savings are self-limiting at best. At some point, someone (probably the government)

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

is going to announce that “x” amount of dollars will be paid for care, and providers will have to scramble to accommodate that amount.

Good oncology practices, both private and hospital-based, will become meticulous about resource management. We, out of necessity, will turn the delivery models upside down. We are not there yet. Models for reform in 2013 have been more about building the “right” models for solid oncology care. Models that evolve for the future will probably be more focused on “manageable models with limited resources” for oncology care.

It is interesting to contrast the business model of dental practices with medical practices. My sister works for a dental practice in New Hampshire. Even the front desk staff knows the costs of opening the doors each day, the resources necessary to provide each service, and the payment ranges for each service. Schedules are carefully managed so that the mix of services that are brought to each doctor each day helps to keep the practice doors open. Additionally, the doctors and the staff work together as a well-oiled machine to keep the doctors doing only what they are trained to do and get paid to do—putting their hands in a patient’s mouth and providing care. You will rarely see one of the doctors chasing charts, patients, or equipment—or waiting. The staff, working as a team, jumps in and provides full support. We haven’t always managed that operational precision in medical practices, but I predict that we will, out of necessity, very soon.

The IOM report on cancer quality raises some interesting points about patient engagement and what pa­ tients should start to expect from Continued on page 13

NOW APPROVED FOR PREVIOUSLY TREATED MCL

INDICATION - IMBRUVICA™ (ibrutinib) is indicated for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This indication is based on overall response rate. An improvement in survival or disease-related symptoms has not been established.

Learn more at www.IMBRUVICA.com IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Hemorrhage - 5% of patients with MCL had ≥ Grade 3 bleeding events (subdural hematoma, gastrointestinal bleeding, and hematuria). Bleeding events including bruising of any grade occurred in 48% of patients with MCL treated with 560 mg daily. The mechanism for the bleeding events is not well understood. Consider the benefit-risk of ibrutinib in patients requiring antiplatelet or anticoagulant therapies and the benefit-risk of withholding ibrutinib for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections - Fatal and non-fatal infections have occurred. At least 25% of patients with MCL had infections ≥ Grade 3, according to NCI Common Terminology Criteria for Adverse Events (CTCAE). Monitor patients for fever and infections and evaluate promptly.

Myelosuppression - Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients. These included neutropenia (29%), thrombocytopenia (17%) and anemia (9%). Monitor complete blood counts monthly.

Renal Toxicity - Fatal and serious cases of renal failure have occurred. Treatmentemergent increases in creatinine levels up to Please review the Brief Summary of full Prescribing Information on the following page. © Pharmacyclics, Inc. 2013 © Janssen Biotech, Inc. 2013 11/13

K08BR13037D

1.5 times the upper limit of normal occurred in 67% of patients and from 1.5 to 3 times the upper limit of normal in 9% of patients.

Periodically monitor creatinine levels.

Maintain hydration.

Second Primary Malignancies - Other malignancies (5%) have occurred in patients with MCL who have been treated with IMBRUVICA™, including skin cancers (4%) and other carcinomas (1%).

Embryo-Fetal Toxicity - Based on findings in animals, IMBRUVICA™ can cause fetal harm when administered to a pregnant woman.

Advise women to avoid becoming pregnant while taking IMBRUVICA™. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS - The most commonly occurring adverse reactions (≥ 20%) in the clinical trial were thrombocytopenia*, diarrhea (51%), neutropenia*, anemia*, fatigue (41%), musculoskeletal pain (37%), peripheral edema (35%), upper respiratory tract infection (34%), nausea (31%), bruising (30%), dyspnea (27%), constipation (25%), rash (25%), abdominal pain (24%), vomiting (23%) and decreased appetite (21%).

*Treatment-emergent decreases (all grades) of platelets (57%), neutrophils (47%) and hemoglobin (41%) were based on laboratory measurements and adverse reactions.

The most common Grade 3 or 4 nonhematological adverse reactions (≥ 5%) were pneumonia (7%), abdominal pain (5%), atrial fibrillation, diarrhea (5%), fatigue (5%), and skin infections (5%). Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients. Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111).

The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients.

DRUG INTERACTIONS CYP3A Inhibitors - Avoid concomitant administration with strong or moderate inhibitors of CYP3A. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA™ dose.

CYP3A Inducers - Avoid co-administration with strong CYP3A inducers.

SPECIAL POPULATIONS - Hepatic Impairment - Avoid use in patients with baseline hepatic impairment.

Brief Summary of Prescribing Information for IMBRUVICATM (ibrutinib) IMBRUVICATM (ibrutinib) capsules, for oral use See package insert for Full Prescribing Information INDICATIONS AND USAGE IMBRUVICA is indicated for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This indication is based on overall response rate. An improvement in survival or disease-related symptoms has not been established [see Clinical Studies (14.1) in full Prescribing Information].

CONTRAINDICATIONS None WARNINGS AND PRECAUTIONS Hemorrhage: Five percent of patients with MCL had Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, and hematuria). Overall, bleeding events including bruising of any grade occurred in 48% of patients with MCL treated with 560 mg daily.

The mechanism for the bleeding events is not well understood.

Consider the benefit-risk of ibrutinib in patients requiring antiplatelet or anticoagulant therapies.

Consider the benefit-risk of withholding ibrutinib for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding [see Clinical Studies (14.1) in full Prescribing Information].

Infections: Fatal and non-fatal infections have occurred with IMBRUVICA therapy. At least 25% of patients with MCL had infections Grade 3 or greater NCI Common Terminology Criteria for Adverse Events (CTCAE) [See Adverse Reactions]. Monitor patients for fever and infections and evaluate promptly.

Myelosuppression: Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients. These included neutropenia (29%), thrombocytopenia (17%) and anemia (9%). Monitor complete blood counts monthly.

Renal Toxicity: Fatal and serious cases of renal failure have occurred with IMBRUVICA therapy. Treatment-emergent increases in creatinine levels up to 1.5 times the upper limit of normal occurred in 67% of patients and from 1.5 to 3 times the upper limit of normal in 9% of patients. Periodically monitor creatinine levels. Maintain hydration.

Second Primary Malignancies: Other malignancies (5%) have occurred in patients with MCL who have been treated with IMBRUVICA, including skin cancers (4%), and other carcinomas (1%).

Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Ibrutinib caused malformations in rats at exposures 14 times those reported in patients with MCL receiving the ibrutinib dose of 560 mg per day. Reduced fetal weights were observed at lower exposures. Advise women to avoid becoming pregnant while taking IMBRUVICA. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations].

ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: • Hemorrhage [see Warnings and Precautions] • Infections [see Warnings and Precautions] • Myelosuppression [see Warnings and Precautions] • Renal Toxicity [see Warnings and Precautions] • Second Primary Malignancies [see Warnings and Precautions] Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to IMBRUVICA in a clinical trial that included 111 patients with previously treated MCL treated with 560 mg daily with a median treatment duration of 8.3 months.

The most commonly occurring adverse reactions (≥ 20%) were thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting and decreased appetite (See TableTables 1 and 2).

The most common Grade 3 or 4 non-hematological adverse reactions (≥ 5%) were pneumonia, abdominal pain, atrial fibrillation, diarrhea, fatigue, and skin infections.

Adverse reactions from the MCL trial (N=111) using single agent IMBRUVICA 560 mg daily occurring at a rate of ≥ 10% are presented in Table 1.

IMBRUVICATM (ibrutinib) capsules Table 1: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with Mantle Cell Lymphoma (N=111) System Organ Class

Preferred Term

Diarrhea Nausea Constipation Abdominal pain Vomiting Stomatitis Dyspepsia Infections and Upper respiratory tract infestations infection Urinary tract infection Pneumonia Skin infections Sinusitis General disorders and Fatigue Peripheral edema administrative site Pyrexia conditions Asthenia Bruising Skin and subcutaneous tissue Rash Petechiae disorders Musculoskeletal and Musculoskeletal pain Muscle spasms connective tissue Arthralgia disorders Respiratory, thoracic Dyspnea Cough and mediastinal Epistaxis disorders Metabolism and Decreased appetite nutritional disorders Dehydration Nervous system Dizziness disorders Headache

Gastrointestinal disorders

All Grades Grade 3 or 4 (%) (%) 5 51 0 31 0 25 5 24 0 23 1 17 0 11 34 14 14 14 13 41 35 18 14 30 25 11 37 14 11 27 19 11 21 12 14 13

0 3 7 5 1 5 3 1 3 0 3 0 1 0 0 4 0 0 2 4 0 0

Table 2: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils in Patients with MCL (N=111)

Platelets Decreased Neutrophils Decreased Hemoglobin Decreased

Percent of Patients (N=111) All Grades (%) Grade 3 or 4 (%) 57 17 47 29 41 9

* Based on laboratory measurements and adverse reactions Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111). The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients.

Patients with MCL who develop lymphocytosis greater than 400,000/mcL have developed intracranial hemorrhage, lethargy, gait instability, and headache. However, some of these cases were in the setting of disease progression.

Forty percent of patients had elevated uric acid levels on study including 13% with values above 10 mg/dL. Adverse reaction of hyperuricemia was reported for 15% of patients.

DRUG INTERACTIONS Ibrutinib is primarily metabolized by cytochrome P450 enzyme 3A. CYP3A Inhibitors: In healthy volunteers, co-administration of ketoconazole, a strong CYP3A inhibitor, increased Cmax and AUC of ibrutinib by 29- and 24-fold, respectively. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 – 1400 mg) given for 28 days with single dose AUC values of 1445 ± 869 ng • hr/mL which is approximately 50% greater than steady state exposures seen at the highest indicated dose (560 mg).

Avoid concomitant administration of IMBRUVICA with strong or moderate inhibitors of CYP3A. For strong CYP3A inhibitors used short-term (e.g., antifungals and antibiotics for 7 days or less, e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin) consider interrupting IMBRUVICA therapy during the duration of inhibitor use. Avoid strong CYP3A inhibitors that are needed chronically. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

IMBRUVICATM (ibrutinib) capsules

IMBRUVICATM (ibrutinib) capsules

Patients taking concomitant strong or moderate CYP3A4 inhibitors should be monitored more closely for signs of IMBRUVICA toxicity [see Dosage and Administration (2.4) in full Prescribing Information].

Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain moderate inhibitors of CYP3A [see Dosage and Administration (2.4), and Clinical Pharmacology (12.3) in full Prescribing Information].

CYP3A Inducers: Administration of IMBRUVICA with strong inducers of CYP3A decrease ibrutinib plasma concentrations by approximately 10-fold.

Avoid concomitant use of strong CYP3A inducers (e.g., carbamazepine, rifampin, phenytoin and St. John’s Wort). Consider alternative agents with less CYP3A induction [see Clinical Pharmacology (12.3) in full Prescribing Information].

USE IN SPECIFIC POPULATIONS Pregnancy: Pregnancy Category D [see Warnings and Precautions].

Risk Summary: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. If IMBRUVICA is used during pregnancy or if the patient becomes pregnant while taking IMBRUVICA, the patient should be apprised of the potential hazard to the fetus.

Animal Data: Ibrutinib was administered orally to pregnant rats during the period of organogenesis at oral doses of 10, 40 and 80 mg/kg/day. Ibrutinib at a dose of 80 mg/kg/day was associated with visceral malformations (heart and major vessels) and increased post-implantation loss. The dose of 80 mg/kg/day in animals is approximately 14 times the exposure (AUC) in patients with MCL administered the dose of 560 mg daily. Ibrutinib at doses of 40 mg/kg/day or greater was associated with decreased fetal weights.

The dose of 40 mg/kg/day in animals is approximately 6 times the exposure (AUC) in patients with MCL administered the dose of 560 mg daily.

Nursing Mothers: It is not known whether ibrutinib 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 IMBRUVICA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: The safety and effectiveness of IMBRUVICA in pediatric patients has not been established.

Geriatric Use: Of the 111 patients treated for MCL, 63% were 65 years of age or older. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse events (atrial fibrillation and hypertension), infections (pneumonia and cellulitis) and gastrointestinal events (diarrhea and dehydration) occurred more frequently among elderly patients.

Renal Impairment: Less than 1% of ibrutinib is excreted renally. Ibrutinib exposure is not altered in patients with Creatinine clearance (CLcr) > 25 mL/min. There are no data in patients with severe renal impairment (CLcr < 25 mL/min) or patients on dialysis [see Clinical Pharmacology (12.3) in full Prescribing Information].

Hepatic Impairment: Ibrutinib is metabolized in the liver and significant increases in exposure of ibrutinib are expected in patients with hepatic impairment. Patients with serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) were excluded from IMBRUVICA clinical trials. There is insufficient data to recommend a dose of IMBRUVICA in patients with baseline hepatic impairment [see Clinical Pharmacology (12.3) in full Prescribing Information].

Females and Males of Reproductive Potential: Advise women to avoid becoming pregnant while taking IMBRUVICA because IMBRUVICA can cause fetal harm [see Use in Specific Populations].

PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information) • Hemorrhage: Inform patients of the possibility of bleeding, and to report any signs or symptoms (blood in stools or urine, prolonged or uncontrolled bleeding).

Inform the patient that IMBRUVICA may need to be interrupted for medical or dental procedures [see Warnings and Precautions].

• Infections: Inform patients of the possibility of serious infection, and to report any signs or symptoms (fever, chills) suggestive of infection [see Warnings and Precautions].

• Renal toxicity: Inform patients of the possibility of renal toxicity. Advise patients to maintain adequate hydration [see Warnings and Precautions].

• Second primary malignancies: Inform patients that other malignancies have occurred in patients with MCL who have been treated with IMBRUVICA, including skin cancers and other carcinomas [see Warnings and Precautions].

• Embryo-fetal toxicity: Advise women of the potential hazard to a fetus and to avoid becoming pregnant [see Warnings and Precautions].

• Inform patients to take IMBRUVICA orally once daily according to their physician’s instructions and that the capsules should be swallowed whole with a glass of water without being opened, broken, or chewed at approximately the same time each day [see Dosage and Administration (2.1) in full Prescribing Information].

• Advise patients that in the event of a missed daily dose of IMBRUVICA, it should be taken as soon as possible on the same day with a return to the normal schedule the following day. Patients should not take extra capsules to make up the missed dose [see Dosage and Administration (2.5) in full Prescribing Information].

• Advise patients of the common side effects associated with IMBRUVICA [see Adverse Reactions]. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION. • Advise patients to inform their health care providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions].

• Advise patients that they may experience loose stools or diarrhea, and should contact their doctor if their diarrhea persists.

Active ingredient made in China.

Distributed and Marketed by: Pharmacyclics, Inc. Sunnyvale, CA USA 94085 and Marketed by: Janssen Biotech, Inc. Horsham, PA USA 19044 Patent http://www.imbruvica.com IMBRUVICA™ is a trademark owned by Pharmacyclics, Inc. ©Pharmacyclics, Inc. 2013 K08BR13131B

Issued: November 2013

Manager–Physician Communication

Tension at the Top…Continued from page 1 penalties from CMS auditors as well as the Health Insurance and Portability and Ac­­ countability Act, the Health Information Technology for Eco­no­ mic and Clinical Health Act, the Office of Inspector General, the Ruth Linné Lander, FACMPE Employee Retirement Income Security Act, the US Department of Labor, and state and local authorities, are al­ways present and increasing.

Facing the transition to Inter­ national Classification of Diseases, Tenth Revision, Clinical Modification and fulfilling meaningful use re­quire­ ments for electronic health records are the focus for the near future. High-deductible health plans and a future of bundled payments to try to bend the untenable growth in the healthcare spending curve also tug on us.

If you live in a highly populated area, hospital systems are jockeying for turf and this is affecting the situation, too.

Internally, staff wants to keep up with their existing standard of living with pay raises and health insurance that doesn’t put onerous burdens on their take-home pay. They are insecure with the news of hospital buyouts of physician practices, group closures, outsourced business, and more global problems such as the debt ceiling, which all make reassurances of their job security very important.

Spending money to empower staff or boost morale is a difficult sell to practice owners. Replacing staff or combining jobs is on the table.

Physicians and staff both feel the pressure of precertifications and other medical insurance policies.

The costs of drugs and medical supplies are ever-changing.

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At times like these, the shortcomings of both physician owners and practice managers become exposed. There are several choices at this point. A healthy choice is admitting your inadequacies and getting up to speed in areas where knowledge is lacking for either the physician or the manager. If time is short, admitting your need and getting outside help in the area(s)

Like growing a plentiful garden, several ingredients are needed to foster a healthy culture so that managers and ownerphysicians do not go to their separate corners. There needs to be good seed for the garden to grow. of immediate need would be positive, too. But, unfortunately, what can often happen are unhealthy decisions being made. Either the physician or the manager do not admit their lack of knowledge or understanding and retreat to their corners, and then the problems really begin.

For the manager, modeling leadership is hard when they feel inadequate internally. They continue to try to take care of and please their staff, their physicians, and outside forces, but trying to do that for too long in this state can bring on burnout and cause managers to abruptly leave the job. Sometimes managers escape to another job,

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

hoping it will be different, but it is rarely different. Sometimes managers just keep treading water, hoping things will change, but they don’t and then they are forced out of the job.

How do we stop this vicious cycle? Like growing a plentiful garden, several ingredients are needed to foster a healthy culture so that managers and owner-physicians do not go to their separate corners.

There needs to be good seed for the garden to grow.

1

First and foremost, the manager must be good seed—the right person in the right job. Taking enough time for decision-making before hiring is vital for possible long-term employment. Checking the manager’s credentials before he or she is hired is a given, but exploring how the manager’s style of operating will fit into the group’s culture should not be overlooked before a job offer is made.

A wrong fit can show up in many ways and cause lots of trouble down the road.

2

Good communication is a vital ingredient between physician and nonphysician leadership. Physicians need to stop and commit enough time to really listen to their managers’ concerns— not a random hallway conversation or a quick meeting while watching the clock.

3

Another ingredient is the need for physicians to respect and appreciate their managers as the assets they are—entrusted with overseeing the practice so it not only remains viable, but that it thrives. A hierarchy in which managers care for the staff and owner-physicians care for the managers is ideal. Instead of allowing more Continued on page 13

From the Editor

Leaving 2013 Behind Continued from page 8 a practice. In 2014, we will hopefully look at those expectations and retool our operations so that we can respond to those expectations.

That may be the catalyst that gets all of us—payers, providers, government, pharmacy, etc—out of the cycle we have been in during the recent years of pilots, several of which are now discovering that they are unattainable or unsustainable without the continuation of start-up funding (which is an unrealistic expectation). At some

point, we will find common ground and a way to make the changes

the patients who need us. Perhaps retooling with more transparency around the costs and using resources in the most effective manner will get us there faster.

The year 2014 will be a watershed year. Hopefully, the lessons we have learned in 2013 will provide the catalyst. We have good practices, and good care, but we can’t keep practicing as we have. Your leadership will be essential. Have a wonderful holiday season, rest up, and get ready to take charge in 2014. l

There is no more money, and discussions of shared savings are self-limiting at best. that are needed without new cash infusion and without penalizing

Manager–Physician Communication

Tension at the Top…Continued from page 12 and more to be piled on the managers to their breaking point, the physicians need to take time to see their managers almost like patients and try to keep their expectations in line with a balanced life for the managers. Throwing money or titles at an overworked manager is not the right ingredient, and it won’t pay off in the long run.

4

Another mistake that owner-physicians make is second-guessing a good manager after having outside conversations with other colleagues where appleto-apple comparisons are just not applicable. Patient demographics can be different, physician competition can be different, managed care penetration can be different,

to mention just a few possible variances. In addition, there are the

physicians will believe the sales pitches and not listen to their own staff who may have concerns. If any of these examples occur, the practice manager is left doing cleanup, explaining actions and trying to get understanding from the physicians on the group’s course. This is wasted time.

Either the physician or the manager do not admit their lack of knowledge or understanding and retreat to their corners, and then the problems really begin.

Conclusion As the decades go by and I get ready to retire, I look over the decades and think of examples from around the country on this topic. I am left with a final, unoriginal thought: It would be so much more powerful and productive if physicians and managers really worked together for the common good. l

many consultants promising physicians the moon hoping that the

CALL TO ACTION

Join our LinkedIn group! See page 55 for details.

December 2013

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Take a bite out of G-CSF acquisition costs*

*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 (tbo-filgrastim) Injection is a leukocyte growth factor indicated for reduction TM

in the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Important Safety Information » Splenic rupture: Splenic rupture, including fatal cases, can occur following the administration of human granulocyte colony-stimulating factors (hG-CSFs). Discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture in patients who report upper abdominal or shoulder pain after receiving GRANIX.

» Acute respiratory distress syndrome (ARDS): ARDS can occur in patients receiving hG-CSFs. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS.

» Allergic reactions: Serious allergic reactions, including anaphylaxis, can occur in patients receiving hG-CSFs. Reactions can occur on initial exposure. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim.

NOW AVAILABLE

GRANIX is a new option in short-acting G-CSF therapy TM

» GRANIX demonstrated a 71% reduction in duration of severe neutropenia (DSN) vs placebo1 – GRANIX significantly reduced DSN when compared to placebo (1.1 days vs 3.8 days; p<0.001)1 – Efficacy was evaluated in a multinational, multicenter, randomized, controlled, Phase III study of chemotherapy-naïve patients with high-risk breast cancer receiving doxorubicin (60 mg/m2 IV bolus)/docetaxel (75 mg/m2)1

» Safety was evaluated in 3 Phase III clinical trials1

Important Safety Information (continued) » 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 colonystimulating 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. GRANIX TM (tbo-filgrastim) Injection Prescribing Information. North Wales, PA: Teva Pharmaceuticals; 2013.

©2013 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. GRANIX is a trademark of Teva Pharmaceutical Industries Ltd. All rights reserved. FIL-40191 October 2013.

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 nonUS-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: Sicor Biotech UAB Vilnius, Lithuania U.S. License No. 1803 Distributed by: Teva Pharmaceuticals USA, Inc. North Wales, PA 19454 Product of Israel FIL-40045 July 2013 This brief summary is based on TBO-003 GRANIX full Prescribing Information.

Best Practices

Exclusive Provider Organizations: Will…Continued from page 1 (EPO) is a health insurance plan with some aspects of a health maintenance organization (HMO) and some aspects of a preferred provider organization (PPO).

The rise of the EPO is a response by insurance companies to potential reduced income through controlled premiums. In seeking additional paths to profit, payers are narrowing their networks to include only providers who fit their algorithm of high patient satisfaction, high preventive care, controlled test ordering, chronic disease management, and controlled hospital admissions.

How interesting to take “the best of the best” and then say “pay them less than everyone else!”

What Are the Hallmarks of an EPO? • May be very attractive to subscribers due to lower premiums and lower copays • There is a big emphasis on preventive care and staying healthy • Subscribers may be required to choose a primary care physician • Subscribers may need referrals for specialist care, even if within the EPO network • Payments are based on fee-for-service, not capitation as with HMOs • There may be some out-of-network benefits for subscribers or subscribers may be responsible for 100% of out-of-network services

• Providers can expect lower reimbursement, but expect payers to promise high volumes of pa­tients due to the restriction of the network • Payers may also lease their EPO network to other plans and payers

single payer to comprise more than 30% of your revenue, you could find yourself at the mercy of a single payer. Who is to say what algorithm any plan might devise that would eliminate you or Mary Pat Whaley, your practice?

FACMPE, CPC Perform an analysis of what accepting the EPO contract could mean for your practice. If the EPO is replacing an existing PPO, substitute the reimbursement you received in the past 12 months for that PPO with what the EPO would pay. Can you live with that revenue?

If the EPO is going to be so prevalent that you can’t possibly turn down participation, what will you do to offset that decrease in revenue? Will you accept as many patients that come your way? Will you add nonphysician providers to increase your capacity for seeing patients without the expense of an additional physician? (Does the EPO credential midlevel providers or would the midlevels work under physicians as supervising physicians?) Will you revisit in-house lab or other ancillary services?

Or, will you stand up like Howard Beale and say, “We’re mad as hell and we’re not going to take this anymore?” l

I recommend that practices limit each payer to no more than 30%.

What Should a Physician Do When Presented with an EPO Contract?

If the selling point of the EPO is an influx of new patients at a reduced rate, or the ability to keep your existing patients at a reduced rate, you should consider very carefully if this is the plan for you.

I recommend that practices limit each payer to no more than 30%.

If you keep each payer to no more than 30% and the network drops you (as we have recently seen with UnitedHealthcare Medicare Advantage plans narrowing their networks), or if a local employer changes medical insurance plans, you could recover. If you allow any

WEB POLL QUESTION Are you prepared for the transition to ICD-10?

Read Karna W. Morrow’s article, “Let the Transition Begin,” in the November issue and visit OPM’s LinkedIn group to join the discussion.

December 2013

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Best Practices

Physicians Push to Increase Awareness of Cancer Overdiagnosis and Overtreatment

By Rosemary Frei, MSc

S

everal prominent physicians are pushing to increase physician awareness of cancer overdiagnosis and overtreatment.

In a recent article, 3 oncologists outlined recommendations made at a March 2012 expert meeting convened by the National Cancer Institute to evaluate ways of reducing treatment or intervention for indolent disease (Esserman LJ, et al.

JAMA.2013;310:797-798.).

The trio penned the “Viewpoint” article to highlight the fact that conditions such as Barrett’s esophagus, ductal carcinoma in situ (DCIS) in the breast, and stand-alone rising prostate-specific antigen (PSA) are often aggressively treated when the evidence—and at least 2 sets of clinical guidelines—indicates that delayed and/or less frequent screening, coupled with less intervention for findings that are likely to represent indolent conditions, may produce similar outcomes.

“Although no physician has the intention to overtreat or overdiagnose cancer, screening and patient awareness have increased the chance of identifying a spectrum of cancers, some of which are not life-threatening,” the authors cautioned in their paper.

Laura J. Esserman, MD, Director of the Carol Franc Buck Breast Care Center, University of California San Francisco, and lead author, emphasized this message in a telephone interview with Oncology Practice Management. She was reflecting her views as well as those of the 2 other authors, Ian M. Thompson, Jr, MD, Glenda and Gary Woods Distinguished Chair in Genitourinary Oncology at The University of Texas Health

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Science Center at San Antonio, and Brian J. Reid, MD, PhD, at the Fred Hutchinson Cancer Research Center, Seattle, Washington.

“Words matter—the word cancer strikes fear in people’s hearts, and we want to make sure that we have the ability to make people aware that, for some conditions, less treatment is the right treatment.”

—Laura J. Esserman, MD

“Words matter—the word cancer strikes fear in people’s hearts, and we want to make sure that we have the ability to make people aware that, for some conditions, less treatment is the right treatment,” said Dr Esserman. “In some cases, there should be a change in words that we use to describe the condition—with the word cancer being reserved for lesions with a reasonable likelihood of lethal progression if left untreated—and in other cases, we have the opportunity to do less screening and treatment, safely.”

Task Force Led the Way The United States Preventive Services Task Force (USPSTF) was one of the first large American organizations to point out that screening only women at risk for breast

ONCOLOGY PRACTICE MANAGEMENT

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cancer—and also once every 2 years rather than annually—is associated with similar outcomes to more frequent screening. It also is associated with reduced biopsy rates, and potentially less overdiagnosis and overtreatment.

The members of the group re­­ viewed the evidence to arrive at their 2009 recommendations (Ann Intern Med. 2009;151:716-726).

They determined that the harms of routine breast cancer screening before age 50 years and after age 75 years outweigh the benefits. The harms include anxiety and unnecessary biopsies in the face of results that turn out to be false positives, and treatment of conditions that would not become clinically apparent during a woman’s lifetime.

Based on the weight of scientific evidence, they also recommended that routine screening mammography should not be carried out in most women aged 40 to 49 years without a conversation about risk and benefit, except when individual women at higher risk and their physicians agree it would be beneficial.

USPSTF members also recommended that mammography be carried out only every other year in women aged 50 to 74 years.

They further recommended against teaching women how to perform breast self-examination.

These recommendations continue to draw strong criticism from groups such as the American College of Radiology.

As a result, physicians have been slow to act on the USPSTF’s message—as shown, for example, by a recently published paper indicating mammography rates did not decrease Continued on page 20

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

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

Primary Endpoint

Secondary Endpoints

• Overall response rate

• • • • • • • •

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

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

NCT#01889186 Reference: ClinicalTrials.gov.

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

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

Best Practices

Physicians Push to Increase Awareness of…Continued from page 18 among women aged 40 years and older between 2008 and 2011 (Pace LE, et al. Cancer. 2013;119:2518-2523).

Nancy Keating, MD, MPH, Associate Professor of Medicine at Brigham and Women’s Hospital, Boston, Massachusetts, led the mammography rates study. She said mammography rates may have dropped somewhat since 2011, but that physicians and patients still need to be warned of the significant dangers of detecting and treating lesions that are not harmful.

“Millions of women have been diagnosed with DCIS, a precancerous lesion that is typically treated aggressively, and now consider themselves to be cancer survivors— when they never even had cancer in the first place,” Dr Keating told Oncology Practice Management.

“The USPSTF team didn’t focus on overdiagnosis but rather focused on other harms, such as anxiety. But a lot of patients aren’t that concerned about anxiety—rather, when we say, ‘We may remove your breast for something that may not harm you’—that’s a bigger deal.”

She said the onus is on individual physicians to communicate to patients the benefits and harms of screening in a way that’s clear and understandable. This is one of the other main points brought out by Dr Esserman and her coauthors.

“Physicians, patients, and the general public must recognize that overdiagnosis is common and occurs more frequently with [routine] cancer screening,” particularly with breast, prostate, lung, and thyroid cancers, they state. “Strategies to reduce detection of indolent disease include reducing low-yield diagnostic evaluations appropriately, reducing the frequency of screening exams, focusing screening on highrisk groups, and raising the threshold for recall and biopsy.”

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In addition, they call for the creation of observational registries for low-malignant-potential lesions, to help develop the knowledge base and technologies needed to accurately discriminate between dangerous and non–life-threatening lesions.

“Routine screening has resulted in unnecessary treatment in our country, because diagnosis always leads to treatment.”

—H. Ballentine Carter, MD

AUA Following Suit It is now well known that many of the prostate lesions flagged by increased PSA levels alone are slowgrowing and indolent. Because millions of men have been overtested and overtreated when watchful waiting would have sufficed, the American Urological Association (AUA) issued new prostate cancer screening guidelines for asymptomatic, average-risk men earlier this year (http://www.auanet.org/education/ guidelines/prostate-cancer-detec tion.cfm).

The organization now recommends against routine PSA testing in average-risk men who are either under age 55 years or over age 70 years. Furthermore, the association recommends that men aged 55 to 69 years should talk to their doctors before deciding whether to undergo PSA testing and, if they opt to go ahead, to have the test every 2 years rather than annually.

“Routine screening has resulted

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

in unnecessary treatment in our country, because diagnosis always leads to treatment, and we need to find a way to reduce that using a more targeted screening approach,” AUA guideline panel chair H. Ballentine Carter, MD, Professor of Urology and Oncology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, told Oncology Practice Management. “We also need to be more circumspect about who does and does not get treated once an anomaly is detected. And I think there’s a paucity of information about whether the new tissue-marker tests are beneficial—we’re trigger-happy in terms of marketing such tests when there’s no absolute proof of benefit.”

Dr Esserman and her colleagues applaud the AUA’s initiative.

“Other groups can follow the process ignited by the leadership in the field of urology for how to delineate and test, and for less-aggressive options for patients with very lowrisk lesions,” she said.

ASCO Weighs In Richard L. Schilsky, MD, Chief Medical Officer of the American Society of Clinical Oncology (ASCO), responded to a request for comment from Oncology Practice Management acknowledging the views on both sides of this issue.

Dr Schilsky said ASCO believes Dr Esserman and her colleagues’ objectives are “laudable” but that patients need to be reassured that early detection is still critically important.

“We do not yet have the ability to say which screen-detected cancers will be indolent, or slow-growing, and which will be aggressive. Until we have better ways of predicting the behavior of these ‘indolent’ tumors,

Continued on page 25

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•Benefit verification •Prior authorization •Appeal support • Delivery coordination of Jakafi

•Co-pay assistance •Free medication programs • Referrals and assistance with independent not-for-profit organizations

PATIENT EDUCATION AND SUPPORT

• Access to trained nurses • Educational information to help teach your patients about their condition and Jakafi Patient packet

•

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

IncyteCARES: ASSISTING PROVIDERS AND PATIENTS IN OBTAINING ACCESS TO JAKAFI Enrollment sent to

95% of patients had insurance coverage for

Patients without insurance coverage were screened for patient assistance eligibility

94% of prior authorizations were approved for

86% of commercially insured patients had co-pays of less than $100/month

Information is based upon 1421 patients enrolled in IncyteCARES between April 1, 2012 and April 1, 2013.

91% of patients referred to the IncyteCARES commercial co-pay assistance program were eligible for assistance Important Safety Information (continued)

•Risk of Infection: Assess patients for signs and symptoms of infection and initiate

appropriate treatment promptly. Serious infections should have resolved before starting therapy with Jakafi • The three most frequent non-hematologic adverse reactions were bruising, dizziness and headache Please see additional Important Safety Information and the Brief Summary of Full Prescribing Information within this ad.

Jakafi is a registered trademark of Incyte Corporation. © 2013, Incyte Corporation. All rights reserved. RUX-1227f 07/13

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

Neutropenia 18.7 5.2 1.9 4.0 0.7 CONTRAINDICATIONS None.

WARNINGS AND PRECAUTIONS Thrombocytopenia, Anemia and Neutropenia Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia. [see Dosage and Administration (2.1) in Full Prescribing Information]. Thrombocytopenia was generally reversible and was usually managed by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary [see Dosage and Administration (2.2) in Full Prescribing Information, and Adverse Reactions]. Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi. Severe neutropenia (ANC less than 0.5 X 109/L) was generally reversible. Withhold Jakafi until recovery [see Adverse Reactions]. Perform a pretreatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated [see Dosage and Administration (2.2) in Full Prescribing Information, and Adverse Reactions]. Risk of Infection Serious bacterial, mycobacterial, fungal and viral infections may occur.

Active serious infections should have resolved before starting therapy with Jakafi. Observe patients receiving Jakafi for signs and symptoms of infection and initiate appropriate treatment promptly. PML Progressive multifocal leukoencephalopathy (PML) has been reported with ruxolitinib treatment for myelofibrosis. If PML is suspected, stop Jakafi and evaluate. Herpes Zoster Advise patients about early signs and symptoms of herpes zoster and to seek treatment as early as possible if suspected [see Adverse Reactions].

ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: • Myelosuppression [see Warnings and Precautions]; • Risk of Infection [see Warnings and Precautions] 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 practice. The safety of Jakafi was assessed in 617 patients in six clinical studies with a median duration of follow-up of 10.9 months, including 301 patients with myelofibrosis in two Phase 3 studies. In these two Phase 3 studies, patients had a median duration of exposure to Jakafi of 9.5 months (range 0.5 to 17 months), with 88.7% of patients treated for more than 6 months and 24.6% treated for more than 12 months. One hundred and eleven (111) patients started treatment at 15 mg twice daily and 190 patients started at 20 mg twice daily. In a double-blind, randomized, placebo-controlled study of Jakafi, 155 patients were treated with Jakafi. The most frequent adverse drug reactions were thrombocytopenia and anemia [see Table 2]. Thrombocytopenia, anemia and neutropenia are dose related effects. The three most frequent non-hematologic adverse reactions were bruising, dizziness and headache [see Table 1]. Discontinuation for adverse events, regardless of causality, was observed in 11.0% of patients treated with Jakafi and 10.6% of patients treated with placebo.

Following interruption or discontinuation of Jakafi, symptoms of myelofibrosis generally return to pretreatment levels over a period of approximately 1 week. There have been isolated cases of patients discontinuing Jakafi during acute intercurrent illnesses after which the patient’s clinical course continued to worsen; however, it has not been established whether discontinuation of therapy contributed to the clinical course in these patients. When discontinuing therapy for reasons other than thrombocytopenia, gradual tapering of the dose of Jakafi may be considered [see Dosage and Administration (2.9) in Full Prescribing Information]. Table 1 presents the most common adverse reactions occurring in patients who received Jakafi in the double-blind, placebo-controlled study during randomized treatment.

Table 1: Adverse Reactions Occurring in Patients on Jakafi in the Double-blind, Placebo-controlled Study During Randomized Treatment Jakafi Placebo (N=155) (N=151) Adverse All All Grade 3 Grade 4 Grades Grade 3 Grade 4 Reactions Gradesa (%) (%) (%) (%) (%) (%) Bruisingb 23.2 0.6 0 14.6 0 0 Dizzinessc 18.1 0.6 0 7.3 0 0 Headache 14.8 0 0 5.3 0 0 Urinary Tract Infectionsd 9.0 0 0 5.3 0.7 0.7 Weight Gaine 7.1 0.6 0 1.3 0.7 0 Flatulence 5.2 0 0 0.7 0 0 Herpes Zosterf 1.9 0 0 0.7 0 0 a National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 b includes contusion, ecchymosis, hematoma, injection site hematoma, periorbital hematoma, vessel puncture site hematoma, increased tendency to bruise, petechiae, purpura c includes dizziness, postural dizziness, vertigo, balance disorder, Meniere’s Disease, labyrinthitis d includes urinary tract infection, cystitis, urosepsis, urinary tract infection bacterial, kidney infection, pyuria, bacteria urine, bacteria urine identified, nitrite urine present e includes weight increased, abnormal weight gain f includes herpes zoster and post-herpetic neuralgia

Description of Selected Adverse Drug Reactions Anemia In the two Phase 3 clinical studies, median time to onset of first CTCAE Grade 2 or higher anemia was approximately 6 weeks. One patient (0.3%) discontinued treatment because of anemia. In patients receiving Jakafi, mean decreases in hemoglobin reached a nadir of approximately 1.5 to 2.0 g/dL below baseline after 8 to 12 weeks of therapy and then gradually recovered to reach a new steady state that was approximately 1.0 g/dL below baseline. This pattern was observed in patients regardless of whether they had received transfusions during therapy. In the randomized, placebo-controlled study, 60% of patients treated with Jakafi and 38% of patients receiving placebo received red blood cell transfusions during randomized treatment. Among transfused patients, the median number of units transfused per month was 1.2 in patients treated with Jakafi and 1.7 in placebo treated patients. Thrombocytopenia In the two Phase 3 clinical studies, in patients who developed Grade 3 or 4 thrombocytopenia, the median time to onset was approximately 8 weeks. Thrombocytopenia was generally reversible with dose reduction or dose interruption. The median time to recovery of platelet counts above 50 X 109/L was 14 days. Platelet transfusions were administered to 4.7% of patients receiving Jakafi and to 4.0% of patients receiving control regimens. Discontinuation of treatment because of thrombocytopenia occurred in 0.7% of patients receiving Jakafi and 0.9% of patients receiving control regimens.

Patients with a platelet count of 100 X 109/L to 200 X 109/L before starting Jakafi had a higher frequency of Grade 3 or 4 thrombocytopenia compared to patients with a platelet count greater than 200 X 109/L (16.5% versus 7.2%). Neutropenia In the two Phase 3 clinical studies, 1.0% of patients reduced or stopped Jakafi because of neutropenia. Table 2 provides the frequency and severity of clinical hematology abnormalities reported for patients receiving treatment with Jakafi or placebo in the placebo-controlled study.

Grade 4 (%) 0 3.3 1.3

a Presented values are worst Grade values regardless of baseline b National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0

Additional Data from the Placebo-controlled Study 25.2% of patients treated with Jakafi and 7.3% of patients treated with placebo developed newly occurring or worsening Grade 1 abnormalities in alanine transaminase (ALT). The incidence of greater than or equal to Grade 2 elevations was 1.9% for Jakafi with 1.3% Grade 3 and no Grade 4 ALT elevations. 17.4% of patients treated with Jakafi and 6.0% of patients treated with placebo developed newly occurring or worsening Grade 1 abnormalities in aspartate transaminase (AST). The incidence of Grade 2 AST elevations was 0.6% for Jakafi with no Grade 3 or 4 AST elevations.

16.8% of patients treated with Jakafi and 0.7% of patients treated with placebo developed newly occurring or worsening Grade 1 elevations in cholesterol. The incidence of Grade 2 cholesterol elevations was 0.6% for Jakafi with no Grade 3 or 4 cholesterol elevations.

DRUG INTERACTIONS Drugs That Inhibit or Induce Cytochrome P450 Enzymes Ruxolitinib is predominantly metabolized by CYP3A4. Strong CYP3A4 inhibitors: The Cmax and AUC of ruxolitinib increased 33% and 91%, respectively, with Jakafi administration (10 mg single dose) following ketoconazole 200 mg twice daily for four days, compared to receiving Jakafi alone in healthy subjects. The half-life was also prolonged from 3.7 to 6.0 hours with concurrent use of ketoconazole. The change in the pharmacodynamic marker, pSTAT3 inhibition, was consistent with the corresponding ruxolitinib AUC following concurrent administration with ketoconazole. When administering Jakafi with strong CYP3A4 inhibitors a dose reduction is recommended [see Dosage and Administration (2.7) in Full Prescribing Information]. Patients should be closely monitored and the dose titrated based on safety and efficacy. Mild or moderate CYP3A4 inhibitors: There was an 8% and 27% increase in the Cmax and AUC of ruxolitinib, respectively, with Jakafi administration (10 mg single dose) following erythromycin, a moderate CYP3A4 inhibitor, at 500 mg twice daily for 4 days, compared to receiving Jakafi alone in healthy subjects. The change in the pharmacodynamic marker, pSTAT3 inhibition was consistent with the corresponding exposure information. No dose adjustment is recommended when Jakafi is coadministered with mild or moderate CYP3A4 inhibitors (eg, erythromycin). CYP3A4 inducers: The Cmax and AUC of ruxolitinib decreased 32% and 61%, respectively, with Jakafi administration (50 mg single dose) following rifampin 600 mg once daily for 10 days, compared to receiving Jakafi alone in healthy subjects. In addition, the relative exposure to ruxolitinib’s active metabolites increased approximately 100%. This increase may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition. No dose adjustment is recommended when Jakafi is coadministered with a CYP3A4 inducer. Patients should be closely monitored and the dose titrated based on safety and efficacy.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies of Jakafi in pregnant women. In embryofetal toxicity studies, treatment with ruxolitinib resulted in an increase in late resorptions and reduced fetal weights at maternally toxic doses.

Jakafi should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30 or 60 mg/kg/day in rats and 10, 30 or 60 mg/kg/day in rabbits. There was no evidence of teratogenicity. However, decreases of approximately 9% in fetal weights were noted in rats at the highest and maternally toxic dose of 60 mg/kg/day. This dose results in an exposure (AUC) that is approximately 2 times the clinical exposure at the maximum recommended dose of 25 mg twice daily. In rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. This dose is approximately 7% the clinical exposure at the maximum recommended dose. In a pre- and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. There were no drug-related adverse findings in pups for fertility indices or for maternal or embryofetal survival, growth and development parameters at the highest dose evaluated (34% the clinical exposure at the maximum recommended dose of 25 mg twice daily).

Nursing Mothers It is not known whether ruxolitinib is excreted in human milk. Ruxolitinib and/or its metabolites were excreted in the milk of lactating rats with a concentration that was 13-fold the maternal plasma. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Jakafi, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use The safety and effectiveness of Jakafi in pediatric patients have not been established. Geriatric Use Of the total number of myelofibrosis patients in clinical studies with Jakafi, 51.9% were 65 years of age and older. No overall differences in safety or effectiveness of Jakafi were observed between these patients and younger patients. Renal Impairment The safety and pharmacokinetics of single dose Jakafi (25 mg) were evaluated in a study in healthy subjects [CrCl 72-164 mL/min (N=8)] and in subjects with mild [CrCl 53-83 mL/min (N=8)], moderate [CrCl 38-57 mL/min (N=8)], or severe renal impairment [CrCl 15-51 mL/min (N=8)]. Eight (8) additional subjects with end stage renal disease requiring hemodialysis were also enrolled. The pharmacokinetics of ruxolitinib was similar in subjects with various degrees of renal impairment and in those with normal renal function. However, plasma AUC values of ruxolitinib metabolites increased with increasing severity of renal impairment. This was most marked in the subjects with end stage renal disease requiring hemodialysis. The change in the pharmacodynamic marker, pSTAT3 inhibition, was consistent with the corresponding increase in metabolite exposure. Ruxolitinib is not removed by dialysis; however, the removal of some active metabolites by dialysis cannot be ruled out. When administering Jakafi to patients with moderate (CrCl 30-59 mL/min) or severe renal impairment (CrCl 15-29 mL/min) with a platelet count between 100 X 109/L and 150 X 109/L and patients with end stage renal disease on dialysis a dose reduction is recommended [see Dosage and Administration (2.8) in Full Prescribing Information]. Hepatic Impairment The safety and pharmacokinetics of single dose Jakafi (25 mg) were evaluated in a study in healthy subjects (N=8) and in subjects with mild [Child-Pugh A (N=8)], moderate [Child-Pugh B (N=8)], or severe hepatic impairment [Child-Pugh C (N=8)]. The mean AUC for ruxolitinib was increased by 87%, 28% and 65%, respectively, in patients with mild, moderate and severe hepatic impairment compared to patients with normal hepatic function. The terminal elimination half-life was prolonged in patients with hepatic impairment compared to healthy controls (4.1-5.0 hours versus 2.8 hours). The change in the pharmacodynamic marker, pSTAT3 inhibition, was consistent with the corresponding increase in ruxolitinib exposure except in the severe (Child-Pugh C) hepatic impairment cohort where the pharmacodynamic activity was more prolonged in some subjects than expected based on plasma concentrations of ruxolitinib. When administering Jakafi to patients with any degree of hepatic impairment and with a platelet count between 100 X 109/L and 150 X 109/L, a dose reduction is recommended [see Dosage and Administration (2.8) in Full Prescribing Information].

Jakafi is a registered trademark of Incyte Corporation. All rights reserved.

U.S. Patent No. 7,598,257 © 2011-2013 Incyte Corporation. All rights reserved.

Issued: June 2013 RUX-1216

Best Practices

Physicians Push to Increase Awareness of…Continued from page 20 we should continue to treat them as indicated by the results of clinical trials in order to prevent spread, recurrence, or death,” Dr Schilsky noted.

He added that changing the established nomenclature is premature, but that “we urge further research on these issues, and careful analyses and collaboration throughout the oncology community.

ASCO welcomes any opportunity to participate in this vitally impor­ tant discussion.”

Dr Esserman and her colleagues agree. “Research and evidence are key to quality cancer care.

Learning when to do less safely is as impor­tant as learning when and how to do more—that is how we can improve the quality of life of

those diagnosed with cancer,” Dr Esserman told Oncology Practice

ical and mental toll of unnecessary screening and treatment. I think

“We do not yet have the ability to say which screen-detected cancers will be indolent, or slowgrowing, and which will be aggressive.”

—Richard L. Schilsky, MD

Management. “We don’t want to forego the opportunity to continue to push forward to reduce the phys-

we can all agree that is a laudable goal—and one that is achievable if we work together.” l

340B Drug Pricing Program

Shift to Hospital-Based Oncology Inadvertently Spurred by the 340B Drug Pricing Program

By Rosemary Frei, MSc

C

ommunity oncology clinics are disappearing at a rate of about 20% a year, according to a report released in mid2013 by the Community Oncology Alliance.1 In their stead, the number and size of hospital systems are increasing.

The deleterious results include reduced access to oncology services in rural or remote regions of the country, and runaway costs on the part of payers. The original vision of the federal government in the 1970s to bring high-quality care to cancer patients in every corner of the country is being rapidly wiped

away from memory.

A significant part of this problem can be traced to the 340B Drug Pricing Program, which was created in 1992 to solve the problem of high drug costs resulting from the Medicaid Drug Rebate Program that was created in 1990.

The intent of 340B was to ensure that patients who were uninsured or indigent could receive adequate medical treatment by discounting the cost of drugs in facilities that serve high numbers of these types of patients.

But an Avalere Health report published in early 2013 document-

December 2013

ed that there are gaping holes in the program.2 As a result, and already as far back as 2006, fully 34% of 340B-enrolled hospitals had a lower percentage of uncompensated care as a percentage of total revenues than the Internal Revenue Service–reported average for hospitals, which was 7%.2 And yet, as of a year ago, about a third of all hospitals in the United States were in the 340B program; collectively, they represented 46% of outpatient medication spending at all hospital facilities in the United States.2 Whether the 340B program— Continued on page 26

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340B Drug Pricing Program

Shift to Hospital-Based Oncology…Continued from page 25 which is run by the Office of Pharmacy Affairs under the Health Resources and Services Administration (HRSA) umbrella—is failing to meet its original mandate because of the government’s lack of willingness or lack of resources is not easy to determine. What is easy for some to determine, though, is who the winners and losers are.

“Who loses are the patients. And who wins are the large hospital systems that are enticing private practices to merge into their big systems, because every time they acquire a physician that means another $2.5 million to $4 million per year of cancer drugs,” Ted Okon, BSc, MBA, Executive Director of the Community Oncology Alliance, told Oncology Practice Management.

“When you apply a large discount on that [large dollar value of cancer drugs] because of the 340B program, that’s a lot of money that immediately falls to the bottom line.

340B is a much-needed, important program, but a lack of oversight and greed are causing significant abuse.”

The Scope of the Problem In a June 2013 report, the Community Oncology Alliance found that in the previous 15 KEY POINTS • Between March 2012 and June 2013, there was a 20% increase in the number of clinics that closed, and a 20% increase in practices that had been purchased by a hospital or had some sort of agreement with a hospital • Between 1998 and 2011, the number of hospitals and clinics enrolled in the 340B program doubled from 8035 to 16,572 • As of a year ago, about 33% of all hospitals in the United States were in the 340B program

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months there had been a 20% increase in the number of clinics that had closed, and a concomitant 20% increase in practices with a hospital agreement or that had been purchased by a hospital.1 Hospitals are very actively en­

rural referral centers, sole community hospitals, and critical-access hospitals. Indeed, 639 such facilities jumped on the 340B bandwagon in the first year after the criteria were expanded.2 The bulk of these, 554, were critical-access hospitals.

“Who loses are the patients. And who wins are the large hospital systems that are enticing private practices to merge into their big systems.”

—Ted Okon, BSc, MBA

gaged in acquiring oncologists and oncologist clinics—and at the same time rushing to enroll in 340B. Community practitioners are barred from enrolling in 340B. The number of hospitals and clinics enrolled in 340B—known in government-speak as “340B entities” or “covered entities”—doubled between 1998 and 2011, from 8035 to 16,572.3 The Avalere Health report—paid for by the Community Oncology Alliance, the Biotechnology Industry Orga­ nization, the Pharmaceutical Research and Manufacturers of America, the National Community Pharmacists Association, the Pharmaceutical Care Management Association, and the National Patient Advocate Foundation— documents that a total of 1673 facilities accounted for the latter figure.

The pace was particularly pronounced in 2010 and 2011. This was due, in large part, to the Affordable Care Act’s expansion of the 340B Drug Pricing Program to cover the outpatient facilities of freestanding cancer hospitals,

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

Another 60 were sole community hospitals, 23 were rural referral centers, and 2 were freestanding cancer hospitals.

These numbers are projected to grow, with the number of facilities signed on to 340B far outpacing the number of uninsured Americans.

The Congressional Budget Office has estimated that the number of uninsured Americans is projected to drop by 45% between early 2013 and early 2019, while the increase in facilities benefiting from 340B will likely keep galloping upward.2 Facilities that benefit also selfpolice, with the onus being on them to notify the government if they become ineligible for 340B. Concomitantly, the fraction of chemotherapy administered in the community setting has fallen from 87% in 2005 to 67% at the end of 2011, according to a 2013 report

by The Moran Company (written communication, May 29, 2013).

“What’s widely acknowledged around Washington, DC, is that the current administration

340B Drug Pricing Program

believes they can control costs more by favoring fewer large, integrated health systems as opposed to a medical delivery system dominated by individual physicians and physician groups,” Mr Okon observed. “But then everybody loses—especially patients with cancer who are faced with higher costs—except for the large hospital systems.”

GAO and Avalere Health Reviews of 340B As a result of the dizzying drive upward in the number of 340B entities, the Government Accountability Office (GAO) reviewed the program. Its findings were published in September 2011.3 Among those findings, 13 of the 29 covered entities that the GAO interviewed had generated revenue from the 340B program that actually exceeded their drug-related costs.3 It also found that HRSA’s oversight was not enough to provide “reasonable assurance” that the covered entities and drug manufacturers were in compliance with the 340B program requirements, including the requirement that drugs purchased at 340B prices would be transferred only to eligible patients.3 The GAO also found that use of the 340B program is on the rise in hospitals, where the risk of improper purchase and use of such drugs is higher, attributable in part to the fact that hospitals treat all patients, regardless of whether they are or are not eligible for 340B drugs.3 HRSA was found to engage in few activities that helped to oversee the 340B program.3 Therefore, the GAO recommended that HRSA take steps to strengthen its oversight of program participation as well as compliance with program requirements.3 This was echoed and expanded in the Avalere Health report.2 Since the GAO report was published, HRSA has begun taking steps to improve its oversight of the program

(eg, officials overseeing the 340B program are now auditing the enrollees and issuing clarifications of definitions of such things as the eligibility of accountable care organizations) there is still a plethora of obvious problem areas. The Avalere Health report states that these problems include the fact that all outpatients of 340B facilities, both insured and

reaching additional low-income patients, or offering new services.”4 The marketplace is indeed mature: this past July, the 20th Annual 340B Coalition Annual Conference took place in Washington, DC, availing attendees with information on how to benefit from the program. At 1 of the conferences a presenter recommended, among other ways to profit from the 340B program, that facilities change chemotherapy protocols to make the most of the difference between the cost and the reimbursement for the medications.

Among those findings, 13 of the 29 covered entities that the GAO interviewed had generated revenue from the 340B program that actually exceeded their drug-related costs.

Reports Confirm Significantly Higher Costs of HospitalBased Cancer Care The differences in cost are highlighted by 2 reports produced in August 2013. Although the reports are not on the topic of the effects of 340B, they do confirm the patterns of an upward push in pricing of hospital-based oncology care. One of the reports was prepared by Milliman, Inc.5 It was commissioned by Genentech.

“Genentech supports patient access to care in all settings. Our primary concern is ensuring that patients who may benefit from our medicines are able to access them, regardless of where they are being treated.

We believe that patients currently treated in community clinics should continue to have access to community-based care,” Charlotte Arnold, spokesperson for Genentech, South San Francisco, CA told Oncology Practice Management.

The Milliman report’s authors compared the costs of chemotherapy in a hospital outpatient setting and in a physician office for commercially insured patients. They used data from Truven Health Analytics from 2009 to 2011 for non–smallcell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer. Their analysis revealed: • The portion of chemotherapy

uninsured, are allowed to be treated with medications bought via the 340B program. Another problem is the resultant market distortion, with physician practices being swallowed by 340B entities—a phenomenon that is “prevalent in the fields of oncology and cardiology.”2 Indeed, the market is so distorted that an entire industry has grown up around providing information on enrolling in and benefiting from the 340B program. For example, a document produced in May 2011 by the National Association of Community Health Centers “is designed to help health centers take advantage of this program,” noting that “use of the 340B program can lead to significant cost savings and revenue generation for health centers.”4 It helpfully points out that “health centers may use the savings in a variety of ways, such as providing medications at a reduced cost or at no cost to some patients, expanding their formulary,

December 2013

Continued on page 28

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340B Drug Pricing Program

Shift to Hospital-Based Oncology…Continued from page 27 that is delivered in the hospital outpatient setting increased between 2009 and 2010 for all 3 types of cancer, rising most sharply in the case of NSCLC, from 18.9% to 23.9%, and also very rapidly in breast cancer, from 18.7% to 20.9%5 • Cost-per-episode for chemotherapy infusions was significantly higher in the hospital outpatient setting than in the physician office setting; the biggest difference was in metastatic NSCLC, at $122,909 versus $82,849 (48.4% higher for the hospital outpatient setting), and the smallest difference was in adjuvant CRC, at $101,060 versus $79,058 (27.8% higher for the hospital outpatient setting)5 • The cost across all sessions in an episode ranged from 39% to 100% higher for the hospital outpatient setting; again, patients with metastatic NSCLC patients incurred the biggest cost difference, at $76,814 versus $38,535 (100% higher), while patients with adjuvant CRC had the smallest difference, at $73,029 versus $52,441 (39.3% higher)5 • The largest contributors to these cost differences were “other” costs on the chemotherapy session day and cytotoxic chemotherapy and biologic drug costs, followed by radiation oncology, imaging, and laboratory services5 • The unit cost for chemotherapy drugs was always significantly higher in the hospital outpatient setting. For patients with metastatic breast cancer, a carboplatin injection averaged $925 in the hospital outpatient setting and $361 in the community setting (256% higher in the hospital outpatient setting). For patients with metastatic CRC, the cetux-

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imab injection was $7363 in the hospital outpatient setting and $3338 in the physician office setting (221% higher in the hospital outpatient setting)5 The other analysis was by employees of The Moran Company, which was paid for by the Community

These numbers are projected to grow, with the number of facilities signed on to 340B far outpacing the number of uninsured Americans.

Oncology Alliance and comprised Medicare data from 2009 to 2011.6 They also found that chemotherapy costs are higher when administered in hospital outpatient departments than in community clinics, with an approximately 50% differential on an annual basis. In addition, the authors documented that patients are given more chemotherapy sessions in hospitals, averaging 9% to 12% more chemotherapy days per beneficiary.

Ms Arnold said that Genentech has recommended a policy proposal that would have Medicare, like approximately half of state Medicaid programs, pay hospitals for the average acquisition cost (AAC) of drugs purchased at the 340B price.

Currently, Medicare pays the average sales price plus a percentage, which is higher than the AAC. “If Medicare reimbursed 340Bparticipating hospitals and clinics by using AAC, a calculation that Medicare can obtain under the current system, the government can save much-needed dollars and hope-

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

fully help extend the solvency of the Medicare program,” Ms Arnold said.

“Under our proposal, Genentech would still pay the same level of 340B discounts that we currently pay. We believe the government could save more than $10 billion over the next 10 years without adjusting payments to the government grantees and public hospitals that serve our nation’s truly indigent population, and without causing currently covered entities to drop out.”

Addressing the Difficulties The American Society of Clinical Oncology Board has commissioned a task force to examine the 340B program and to develop a position on the current state of affairs. The American Cancer Society neither has an official position nor is developing one.

Mr Okon believes the situation deserves far more attention.

“We have a real cancer-care crisis in this country that few people understand. And it’s getting worse by the day.” l References

1. Community Oncology Practice Impact Report.

The changing landscape of cancer care. June 25, 2013. www.communityoncology.org/UserFiles/Com munity_Oncology_Practice_Impact_Report_6-2513F.pdf. Accessed December 3, 2013.

2. Avalere Health. The 340B drug discount program: a review and analysis of the 340B program. 2013. www.bio.org/sites/default/files/340B%20White%20 Paper%20FINAL.pdf. Accessed December 3, 2013.

3. United States Government Accountability Office Report to Congressional Committees. Drug pricing: manufacturer discounts in the 340B program offer benefits, but federal oversight needs improvement. www.gao.gov/assets/330/323702.pdf. Accessed December 3, 2013.

4. National Association of Community Health Centers. Understanding the 340B program: A primer for health centers. May 2011. https://nachc.com/ client/documents/5.11%20340%20Manual%20 Primer%20for%20Health%20Centers2.pdf. Accessed December 3, 2013.

5. Fitch K, Iwasaki K, Pyenson B. Comparing episode of cancer care costs in different settings: An actuarial analysis of patients receiving chemotherapy. August 2013. www.milliman.com/uploaded Files/insight/2013/chemotherapy-site-of-service.pdf.

Accessed December 3, 2013.

6. The Moran Company. Cost differences in cancer care across settings. August 2013. https://media.gractions. comE5820F8C11F80915AE699A1BD4FA0948B6 285786/adebd67d-dcb6-46e0-afc3-7f410de24657.pdf.

Accessed December 3, 2013.

IOM Call to Action

Institute of Medicine Recommends Measures to Achieve High-Quality Cancer Care

By Rosemary Frei, MSc

I

n September, the Institute of Medicine (IOM) released its report, “Delivering HighQuality Cancer Care: Charting a New Course for a System in Crisis,” which included recommendations aimed at ensuring that there is accessible, affordable, and high-caliber oncology care in the United States for the foreseeable future.

But with the shifting fiscal landscape in the country, including the recent tussles of the government shutdown over Obamacare and raising the federal debt ceiling, as well as scheduled cuts to the Medicare Physician Fee Schedule, is it foreseeable whether the funds will be made available to achieve those laudable objectives?

Patrick Cobb, MD, who is president of the Community Oncology Alliance and was not a member of the committee that wrote the report, has doubts.

“The recommendations are going to require a significant financial

KEY POINTS • The annual cancer incidence has surpassed 1.6 million and the prevalence has reached approximately 14 million • The cost of cancer care rose from $72 billion in 2004 to $125 billion in 2010, and is on track to reach $173 billion within 7 years • The number of Americans aged 65 years and older is projected to double between now and 2030 • There will be an estimated 18 million cancer survivors in 2022

investment by private payers, by government, by universities, by hospitals, and by private clinics—

the initiative and start the ball rolling with respect to things that are in the best interests of our

“With the fiscal environment we have now at the federal and state levels, I don’t think there’s going to be a financial commitment to making these things happen.”

—Patrick Cobb, MD

and with the fiscal environment we have now at the federal and state levels, I don’t think there’s going to be a financial commitment to making these things happen,” Dr Cobb, who is a hematologist in private practice affiliated with the St. Vincent Frontier Cancer Center in Billings, Montana, told Oncology Practice Management.

He also said that the report’s proposal to shift cancer care reimbursement away from fee-for-service to rewarding best practices will be “incredibly difficult” to accomplish.

Others, however, are optimistic that a path forward can be found.

“We need to figure out ways to reduce costs and make effective treatments more universally available,” said Ismail Jatoi, MD, PhD, FACS, professor and chief of the division of surgical oncology and endocrine surgery at the Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio, and also not a member of the report committee. “I think doctors can take

December 2013

patients. We can’t rely on government because they may not be able to do it.”

Ensuring Quality in the Face of Ballooning Demand In 1999, another IOM report, “Ensuring Quality Cancer Care,” addressed gaps in providing ideal cancer treatment to every patient in the United States. Since then, however, the gaps have grown rather than shrunk. The annual cancer incidence has surpassed 1.6 million and the prevalence has reached approximately 14 million. At the same time, the cost of care rose from $72 billion in 2004 to $125 billion in 2010, and is on track to reach $173 billion within 7 years.

Meanwhile, the number of Americans who are 65 years of age and older is projected to double between now and 2030. This group will account for a large portion of the increased cancer burden, including diagnoses, deaths, and survivors. There will be 18 mil-

Continued on page 34

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Indication XTANDI® (enzalutamide) capsules is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.

Important Safety Information Contraindications-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.

Warnings and Precautions-In the randomized clinical trial, seizure occurred in 0.9% of patients on XTANDI. No patients on the placebo arm experienced seizure. Patients experiencing a seizure were permanently discontinued from therapy. All seizures resolved. Patients with a history of seizure, taking medications known to decrease the seizure threshold, or with other risk factors for seizure were excluded from the clinical trial. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others.

Adverse Reactions-The most common adverse drug reactions (≥5%) reported in patients receiving XTANDI in the randomized clinical trial were asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and in 6% on placebo (no Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients and 2% on placebo. One percent of XTANDI patients compared to 0.3% on placebo died from infections or sepsis. Falls or injuries related to falls occurred in 4.6% of XTANDI patients vs 1.3% 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% 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. Co-administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If co-administration of XTANDI cannot be avoided, reduce the dose of XTANDI. Co-administration of XTANDI with strong or moderate CYP3A4 and CYP2C8 inducers can alter the plasma exposure of XTANDI and should be avoided if possible.

Effect of XTANDI on Other Drugs: XTANDI is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. Avoid CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs.

If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see adjacent pages for brief summary of Full Prescribing Information.

© 2013 Astellas Pharma US, Inc. All rights reserved. 013A-700-7126 05/13 Printed in USA

XtandiHCP.com

XTANDI, Astellas, and the flying star logo are registered trademarks of Astellas Pharma Inc. XTANDI Access ServicesSM is a component of Astellas Access ServicesSM.

(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

IOM Call to Action

Institute of Medicine Recommends…Continued from page 29 lion cancer survivors in 2022, the authors of the new report estimate.

“We presented our report in the frame of a crisis—that if we don’t get our act together we’re going to be in deep trouble in terms of being able to deliver care the way we’re delivering it now to an increased number of patients,” Patricia A. Ganz, MD, director of the division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center, University of California, Los Angeles, and the chair of the committee that wrote the report, told Oncology Practice Management.

“We need to increase the efficiency, quality, and patient-centeredness of cancer care. Currently we have a very inefficient, uncoordinated healthcare system that’s driven by the fee-for-service environment.”

The way to accomplish this, according to Dr Ganz and the other committee members, is through a 6-pronged strategy aimed at attaining engaged patients; an adequately staffed, trained, and coordinated workforce; evidence-based cancer care; a learning healthcare information technology (IT) system for cancer; translation of evidence into

clinical practice, quality measurement, and performance improvement; and accessible and affordable cancer care.

The report asserts that the main ways to achieve these objectives are: • Funding from government and other sources both to improve

ment models by the Centers for Medicare & Medicaid Services and other payers • Improving end-of-life care via clinician training in end-oflife communication and more emphasis on palliative care, psychosocial support, and timely

“We presented our report in the frame of a crisis—that if we don’t get our act together we’re going to be in deep trouble in terms of being able to deliver care the way we’re delivering it now to an increased number of patients.”

—Patricia A. Ganz, MD

the development and dissemination of decision aids for patients that provide understandable information on all aspects of cancer care and to increase clinicians’ communication skills, and development of innovative pay-

referral to hospices • Improving coordination be­­ tween members of the cancer care team, eliminating reimbursement and scope-of-practice barriers to this level of coordiContinued on page 36

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IOM Call to Action

Institute of Medicine Recommends…Continued from page 34 nation, and federal government funding of the National Health Care Workforce Commission • Ensuring that all cancer care clinicians have appropriate core competencies • Expanding the breadth and depth of data collected in randomized controlled trials and observational studies on cancer care for older adults and people with several comorbidities • Developing an “ethically sound” learning healthcare IT system that allows real-time analysis of data from patients with cancer in a broad array of care settings • Coordinating efforts between government and professional societies to develop a national quality reporting program for cancer care • Reducing disparities in access to cancer care for vulnerable and underserved populations • Increasing the affordability of cancer care by leveraging existing efforts to reform payment and eliminate waste

Can It Be Done?

“This is an ambitious list of goals.

But there are none that don’t reso-

nate with anyone who’s either a cancer caregiver or who has had a family member with cancer,” said Walter J. Curran, MD, Executive Director of the Winship Cancer Institute of Emory University, Atlanta, GA, and not a member of the report committee. He cited, in particu-

“This is an ambitious list of goals. But there are none that don’t resonate with anyone who’s either a cancer caregiver or who has had a family member with cancer.”

—Walter J. Curran, MD

lar, the importance of making sure patients are provided with clinical and cost information associated with treatment options, and of expanding the breadth and depth of cancer research data. “This document has

come out when there’s a federal shortage of research funding. But there are still research dollars; it’s a matter of how they’re prioritized.”

Drs Curran and Jatoi believe that the committee hit all the right notes, including the emphasis on increasing both the cohesiveness of cancer care teams and the understanding of how best to support patients in their choices of treatment.

However, Dr Cobb noted that only 1 member of the report committee represented community oncology: Michael Neuss, MD, who was in private practice in Cincinnati for 25 years before joining the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, where he is now a professor and chief medical officer.

Dr Cobb believes the report “is a very good place to start. But now comes the hard part—determining and implementing the individual steps that are needed to make the recommendations a reality, especially for a community oncologist in Billings, Montana, who sees 25 patients in his office every day.

You’ve got to make things less complicated rather than more complicated. And that’s a real challenge.” l

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ONCOLOGY PRACTICE MANAGEMENT

I December 2013

Wealth Management With Lawrence B. Keller

Checklist to Cut Your 2013 Taxes

By Andrew D. Schwartz, CPA; and Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF

A

lthough 2013 tax rates have increased for certain high-income taxpayers, there is still time to take advantage of several tax-saving opportunities before December 31. Below are 10 ways to cut your 2013 tax bill and a few things to consider when planning for 2014.

1

Increase your 401(k) and 403(b) contributions if you haven’t been contributing at the maximum rate all year. This year you can put up to $17,500 into your 401(k) or 403(b) plan. Anyone aged ≥50 years by December 31 can put away an additional $5500 (for a total of $23,000).

Contributing to a 401(k) or 403(b) plan at work is one of the best tax shelters available to you during your working years. You might also start thinking about setting your 2014 retirement savings goals.

2

If you’re self-employed, consider setting up a Solo 401(k) by December 31. A Solo 401(k) plan allows a self-employed person to reach the $51,000 retirement plan maximum with less income than with a SEP-IRA. It also allows a person aged ≥50 years to put an additional $5500 (for a total of $56,500) into a retirement plan for 2013.

3

Take a look at your withholdings and instruct your employer to withhold additional taxes if you haven’t had enough taxes withheld during the year to avoid an underpayment penalty. Look at the Internal Revenue Service’s (IRS) withholding calculator online to set your withholdings for 2014.

4

Consider selling your investments held in nonretirement accounts that have decreased in

8

value. Your capital losses can offset other capital gains realized during the year (including those from your mutual funds). Excess losses can then be used to offset up to $3000 of wages and other income.

However, make sure to wait at least 31 days before buying back any security sold at a loss, or the IRS will disallow the loss under the “wash sale” rules.

For gifts of money, making your donation by credit card before December 31 allows you to deduct the donation on this year’s return, even if you don’t pay your credit card bill until 2014. You always have the option of Lawrence B. Keller donating appreciated investments to charities. You get to claim your donation based on the value of the assets donated, without paying any capital gains taxes on the appreciation.

5

Consider selling your investments that have increased in value if you are in the 2 lowest tax brackets.

You should consider this because the long-term capital gains rate for you will be 0%. You can then buy back those securities, and the “cost-basis” will be the higher amount. This strategy will save you taxes in the future when you sell these securities.

Just make sure that the capital gains realized do not push you out of the 10% or 15% tax brackets, or you will be taxed on those gains that fall outside of those tax brackets.

9

Prepay your projected state tax shortfall if you will be itemizing your deductions and not subject to the alternative minimum tax. Because of the higher tax rates enacted for 2013, there is a better chance that you won’t be subject to the alternative minimum tax (AMT) this year.

10

Prepay and pay off your medical bills if your total medical expenses exceed 10% of your income and you itemize. Please note that this threshold remains 7.5% for people aged >65 years, whereas the threshold for everyone increased from 7.5% to 10%.

During December, you should evaluate whether you will save any taxes by postponing 2013 income or deductions into 2014 or by accelerating 2014 income or deductions into 2013. Although many factors should be evaluated before making your final decision, a few items to keep in mind include: • For 2013, a single person will itemize once allowable deductions exceed $6100 and a married couple will itemize once allow-

6

Send in your January 2014 mortgage payment early enough so it will be processed before December 31, 2013. By sending in your payment a few weeks early, you can deduct the interest portion of that payment a full year earlier.

7

Clean out your closets and donate your clothing and household items to a charitable organization, because noncash contributions are deductible if you itemize.

Don’t forget to get a receipt, and you should make a list of each item donated, along with its condition, and take a few pictures as well. Remember, only donations of clothing and household items that are in “good condition or better” qualify for a deduction.

December 2013

Continued on page 40

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Wealth Management

Checklist to Cut Your 2013 Taxes…Continued from page 37 able deductions exceed $12,200 • A taxpayer is no longer subject to Social Security or to self-employment taxes once wages and net self-employment earnings exceed $113,700 in 2013 and $117,000 in 2014 • The AMT exemption amounts have been permanently “patched” for 2013 and for future years. For 2013, the exemption amounts are $51,900 for single individuals and heads of household and $80,800 for married couples filing a joint return and surviving spouses. For tax year 2014, the amount is $52,800 ($82,100 for married couples filing jointly) • Obamacare surtaxes will continue to affect higher earners with a 3.8% surtax on net investment income and an additional Medicare tax of 0.9% • Miscellaneous itemized deductions, such as unreimbursed employee business expenses, are only deductible to the extent that they exceed 2% of your adjusted gross income. Items paid with credit cards are deductible in the year that they are charged • You should plan for a continuation of the 39.6% tax bracket for the highest earners (individuals earning more than $406,750 and married couples earning more than $457,600 in 2014), the phase out of personal exemptions, a limitation on itemized deductions, and a 20% tax rate on long-term capital gains and qualified dividends.

Don’t Forget About IRAs Even if you are covered under a retirement plan at work, you and your spouse can each contribute up to $5500 into a traditional IRA or Roth IRA for 2013 and 2014, as long as your combined wages and net self-employment income exceed the

40

I

total amount contributed. Anyone aged ≥50 years can contribute an extra $1000, increasing the total allowable contribution to $6500.

Here is some good news for people looking to contribute to a Roth IRA. The amount you can earn and still contribute to a Roth has increased by $3000 for married couples and by $2000 for single individuals. When the phase out begins, the income amounts for single individuals is $114,000 and for married couples, $181,000. At the end of the phase out, the income amounts become $129,000 for individuals and $191,000 for married couples.

Even if you are covered under a retirement plan at work, you and your spouse can each contribute up to $5500 into a traditional IRA or Roth IRA for 2013 and 2014.

If your income is too high for a Roth IRA, don’t forget that the rules changed a few years back, eliminating the income limitation as of 2010 for people converting their IRAs to a Roth IRA. This tax law change provides high-income taxpayers with a great opportunity to get money into these tax-free investment accounts.

For more information, please check out the article, “Think You Earn Too Much Money to Contribute to a Roth IRA? Guess Again,” which appeared in the March 2013 issue of Oncology Practice Management.

In addition, if you are married

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

and your spouse is not covered under either an employer-sponsored or self-employed retirement plan during the year, the 2013 phaseout range for your spouse making a deductible IRA contribution has increased to $181,000 to $191,000, which is identical to the Roth IRA phase-out limits.

Concusion This article provides 10 potential tax-saving opportunities for 2013 and a few things to consider in 2014. The key is to take the time to evaluate which of these concepts, if any, may work in your situation.

Almost everyone is familiar with the old adage about life’s 2 certainties: taxes, like death, are inevitable. But why pay more in taxes than you have to? In fact, Judge Billings Learned Hand once said “Anyone may so arrange his affairs that his taxes shall be as low as possible; he is not bound to choose that pattern which will best pay the Treasury; there is not even a patriotic duty to increase one’s taxes.” l About the Authors Andrew D. Schwartz, CPA, is a part­ ner in the Boston CPA firm Schwartz & Schwartz, P.C. and is the founder of the MDTAXES Network (www.mdtaxes. com), a national network of CPAs who specialize in tax and accounting services for healthcare professionals and their practices. He can be reached for ques­ tions or comments at 800-471-0045 or by e-mail at Andrew@mdtaxes.com.

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

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

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

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

Printed in USA

V-10-0196

11/10

Drug Coding Supplied by RJ Health Systems

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

The following sections include: • Associated ICD-9-CM codes used for the classification of lymphoma • Drugs that have been FDA approved in the treatment of lymphoma • Drugs that are Compendia-listed for off-label use for lymphoma 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 lymphoma. However, drugs in the FDA-approved section are FDA approved for at least 1 of the lymphoma ICD-9-CM codes but may also have Compendia-listed uses as well

Associated ICD-9-CM codes for the treatment of lymphoma: The following fifth-digit subclassification is for use with categories 200-202:

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 200 Lymphosarcoma and reticulosarcoma and other specified malignant tumors of lymphatic tissue

200.0 Reticulosarcoma

200.1 Lymphosarcoma

200.2 Burkitt’s tumor or lymphoma

200.3 Marginal zone lymphoma

200.4 Mantle cell lymphoma

200.5 Primary central nervous system lymphoma

200.6 Anaplastic large cell lymphoma

200.7 Large cell lymphoma

200.8 Other named variants

Lymphoma (malignant):

lymphoplasmacytoid type

mixed lymphocytic-histiocytic (diffuse)

Lymphosarcoma, mixed cell type (diffuse)

Reticulolymphosarcoma (diffuse) 201 Hodgkin’s disease

201.0 Hodgkin’s paragranuloma

201.1 Hodgkin’s granuloma

201.2 Hodgkin’s sarcoma

201.4 Lymphocytic-histiocytic predominance

42

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ONCOLOGY PRACTICE MANAGEMENT

I December 2013

Drug Coding

201.5 Nodular sclerosis

Hodgkin’s disease, nodular sclerosis: NOS

cellular phase

201.6 Mixed cellularity

201.7 Lymphocytic depletion

Hodgkin’s disease, lymphocytic depletion: NOS

diffuse fibrosis

reticular type

201.9 Hodgkin’s disease, unspecified

Hodgkin’s: Malignant:

disease NOS: lymphogranuloma

lymphoma NOS: lymphogranulomatosis 202 Other malignant neoplasms of lymphoid and histiocytic tissue

202.0 Nodular lymphoma

202.1 Mycosis fungoides

202.2 Sézary’s disease

202.3 Malignant histiocytosis

202.4 Leukemic reticuloendotheliosis

202.5 Letterer-Siwe disease

202.6 Malignant mast cell tumors

202.7 Peripheral T-cell lymphoma

202.8 Other lymphomas

Lymphoma (malignant) NOS diffuse Excludes: benign lymphoma (229.0)

202.9 Other and unspecified malignant neoplasms of lymphoid and histiocytic tissue

Follicular dendritic cell sarcoma

Interdigitating dendritic cell sarcoma

Langerhans cell sarcoma

Malignant neoplasm of bone marrow NOS

FDA-approved for lymphoma

Compendia listed off-label uses for lymphoma

Possible CPT ® administration codes

Generic (brand) name

HCPCS code: code description

acyclovir (Zovirax)

J0133: Injection, acyclovir, 5 mg

√

96365

acyclovir (Zovirax)

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

√

n/a

aldesleukin (Proleukin)

J9015: Injection, aldesleukin, per single-use vial

√

96409

bacillus Calmette-Guerin (BCG vaccine)

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

√

90471, 90472

December 2013

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Drug Coding

44

I

FDA-approved for lymphoma

Compendia listed off-label uses for lymphoma

Possible CPT ® administration codes

Generic (brand) name

HCPCS code: code description

bacillus Calmette-Guerin (Tice BCG, TheraCys)

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

bendamustine (Treanda)

J9033: Injection, bendamustine hydrochloride 1 mg

√

96413

betamethasone (Celestone)

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

√

N/A

betamethasone acetate and betamethasone sodium phosphate (Celestone Soluspan)

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

√

11900, 11901, 20600, 20605, 20610, 96372

bexarotene (Targretin)

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

√

N/A

bleomycin (Blenoxane)

J9040: Injection, bleomycin sulfate, 15 units

√

96401, 96409

bortezomib (Velcade)

J9041: Injection, bortezomib, 0.1 mg

√

96409

brentuximab vedotin (Adcetris)

J9042: Injection, brentuximab vedotin, 1 mg

√

96413

carboplatin (Paraplatin)

J9045: Injection, carboplatin, 50 mg

carmustine (BiCNU)

J9050: Injection, carmustine, 100 mg

√

96413, 96415

chlorambucil (Leukeran)

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

√

N/A

chlorambucil (Leukeran)

S0172: Chlorambucil, oral, 2 mg

√

N/A

cisplatin (Platinol AQ)

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

√

96409, 96413, 96415

cladribine (Leustatin)

J9065: Injection, cladribine, per 1 mg

√

96413, 96415

cortisone (Cortef)

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

√

N/A

cyclophosphamide (Cytoxan)

J8530: Cyclophosphamide, oral, 25 mg

√

N/A

cyclophosphamide (Cytoxan)

J9070: Cyclophosphamide, 100 mg

√

96409, 96413, 96415

cytarabine (Cytosar-U)

J9100: Injection, cytarabine, 100 mg

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

√

√

√

51720

96409, 96413, 96415

96409, 96413, 96415, 96450

Drug Coding

FDA-approved for lymphoma

Compendia listed off-label uses for lymphoma

Possible CPT ® administration codes

Generic (brand) name

HCPCS code: code description

dacarbazine (DTIC-Dome)

J9130: Dacarbazine, 100 mg

daunorubicin (Cerubidine)

J9150: Injection, daunorubicin, 10 mg

√

96409, 96413

daunorubicin citrate liposome (DaunoXome)

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

√

96413

dexamethasone (Decadron)

J8540: Dexamethasone, oral, 0.25 mg

√

N/A

dexamethasone (Decadron)

J1100: Injection, dexamethasone sodium phosphate, 1 mg

√

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

doxorubicin (Adriamycin PFS)

J9000: Injection, doxorubicin hydrochloride, 10 mg

√

96409

doxorubicin hydrochloride liposomal (Doxil)

J9002: Injection, doxorubicin hydrochloride, liposomal, doxil, 10 mg (code no longer payable

by Medicare effective 7/1/13)

√

96413

doxorubicin hydrochloride liposomal (Doxil)

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

√

96413

epirubicin (Ellence)

J9178: Injection, epirubicin hydrochloride, 2 mg

√

96409, 96413

etanercept (Enbrel)

J1438: Injection, etanercept, 25 mg (code may be used for Medicare when drug administered under the direct supervision of a physician; not for use when drug is self-administered)

√

96372

etoposide (Vepesid)

J8560: Etoposide, oral, 50 mg

√

N/A

etoposide (Toposar)

J9181: Injection, etoposide, 10 mg

√

96413, 96415

fludarabine (Fludara)

J9185: Injection, fludarabine phosphate, 50 mg

√

96413

gallium nitrate (Ganite)

J1457: Injection, gallium nitrate, 1 mg

√

96365, 96366

ganciclovir (Cytovene)

J1570: Injection, ganciclovir sodium, 500 mg

√

96365

gemcitabine (Gemzar)

J9201: Injection, gemcitabine hydrochloride, 200 mg

√

96413

hydrocortisone (Solu-Cortef)

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

96409, 96413

√

96365, 96366, 96372, 96374

√

December 2013

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Drug Coding

46

I

FDA-approved for lymphoma

Compendia listed off-label uses for lymphoma

Possible CPT ® administration codes

Generic (brand) name

HCPCS code: code description

hydroxyurea (Hydrea)

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

√

N/A

hydroxyurea (Hydrea)

S0176: Hydroxyurea, oral, 500 mg

√

N/A

ibritumomab tiuxetan for yttrium Y-90 (Zevalin Y-90)

A9543: Yttrium Y-90 ibritumomab tiuxetan, therapeutic, per treatment dose, up to 40 millicuries

√

79403

ibrutinib (Imbruvica)

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

√

N/A

ibrutinib (Imbruvica)

C9399*: Unclassified drugs or biological (hospital OPPS use only)

√

N/A

idarubicin (Idamycin PFS)

J9211: Injection, idarubicin hydrochloride, 5 mg

√

96409

ifosfamide (Ifex)

J9208: Injection, ifosfamide, 1 gram

√

96413, 96415

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

interferon alfa-n3 (Alferon N)

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

iodine I-131 (Bexxar)

A9544: Iodine I-131 tositumomab, diagnostic, per study dose

irinotecan (Camptosar)

J9206: Injection, irinotecan, 20 mg

lenalidomide (Revlimid)

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

√

N/A

lenalidomide (Revlimid)

C9399*: Unclassified drugs or biological (hospital OPPS use only)

√

N/A

leucovorin calcium (Wellcovorin)

J0640: Injection, leucovorin calcium, per 50 mg

lomustine (CeeNU)

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

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

√

96365

√ √

√ √

11900, 11901

96413, 96415

96372, 96374, 96409 N/A

Drug Coding

Compendia listed off-label uses for lymphoma

Generic (brand) name

HCPCS code: code description

FDA-approved for lymphoma

lomustine (CeeNU)

S0178: Lomustine, oral, 10 mg

√

lymphocyte immune globulin antithymocyte globulin (Atgam)

J7504: Lymphocyte immune globulin, antithymocyte globulin, equine, parenteral, 250 mg

mechlorethamine (Mustargen)

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

melphalan (Alkeran)

J8600: Melphalan, oral, 2 mg

√

N/A

melphalan (Alkeran)

J9245: Injection, melphalan hydrochloride, 50 mg

√

96409, 96413

mercaptopurine (Purinethol)

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

√

N/A

mercaptopurine (Purinethol)

S0108: Mercaptopurine, oral, 50 mg

√

N/A

methotrexate

J8610: Methotrexate, oral, 2.5 mg

√

N/A

methotrexate

J9250: Methotrexate sodium, 5 mg

√

96372, 96374, 96401, 96409, 96450

methotrexate

J9260: Methotrexate sodium, 50 mg

√

96372, 96374, 96401, 96409, 96450

methylprednisolone (Medrol)

J7509: Methylprednisolone, oral, per 4 mg

√

N/A

methylprednisolone acetate (Depo-Medrol)

J1020: Injection, methylprednisolone acetate, 20 mg

√

11900, 11901, 20600, 20605, 20610, 96372

methylprednisolone actetate (Depo-Medrol)

J1030: Injection, methylprednisolone acetate, 40 mg

√

11900, 11901, 20600, 20605, 20610, 96372

methylprednisolone acetate (Depo-Medrol)

J1040: Injection, methylprednisolone acetate, 80 mg

√

11900, 11901, 20600, 20605, 20610, 96372

methylprednisolone sodium succinate (Solu-Medrol)

J2920: Injection, methylprednisolone sodium succinate, up to 40 mg

√

96365, 96366, 96372, 96374

methylprednisolone sodium succinate (Solu-Medrol)

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

√

96365, 96366, 96372, 96374

mitoxantrone (Novantrone)

J9293: Injection, mitoxantrone hydrochloride, per 5 mg

nelarabine (Arranon)

J9261: Injection, nelarabine, 50 mg

oxaliplatin (Eloxatin)

J9263: Injection, oxaliplatin, 0.5 mg

N/A √

96365, 96366

96409

√

√

96409, 96413 96413, 96415

√ √

December 2013

Possible CPT ® administration codes

I

96413, 96415

www.OncPracticeManagement.com

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Drug Coding

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FDA-approved for lymphoma

Compendia listed off-label uses for lymphoma

Possible CPT ® administration codes

Generic (brand) name

HCPCS code: code description

paclitaxel (Taxol)

J9265: Injection, paclitaxel, 30 mg

√

96413, 96415

pegaspargase (Oncaspar)

J9266: Injection, pegaspargase, per single-dose vial

√

96401, 96413, 96415

pentostatin (Nipent)

J9268: Injection, pentostatin, per 10 mg

√

96409, 96413

pralatrexate (Folotyn)

J9307: Injection, pralatrexate, 1 mg

√

96409

prednisolone (Millipred, Prelone)

J7510: Prednisolone, oral, per 5 mg

√

N/A

prednisone (eg, Orasone, Deltasone)

J7506: Prednisone, oral, per 5 mg

√

N/A

procarbazine (Matulane)

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

√

N/A

procarbazine (Matulane)

S0182: Procarbazine hydrochloride, oral, 50 mg

√

N/A

rituximab (Rituxan)

J9310: Injection, rituximab, 100 mg

√

96413, 96415

romidepsin (Istodax)

J9315: Injection, romidepsin, 1 mg

√

96413, 96415

temsirolimus (Torisel)

J9330: Injection, temsirolimus, 1 mg

√

96413

teniposide (Vumon)

Q2017: Injection, teniposide, 50 mg

√

96413, 96415

thiotepa (Thiotepa)

J9340: Injection, thiotepa, 15 mg

√

51720, 96409

tositumomab (Bexxar 131 Iodine)

A9545: Iodine I-131 tositumomab, therapeutic, per treatment dose

√

79403

vinblastine (Velban)

J9360: Injection, vinblastine sulfate, 1 mg

√

96409

vincristine (Vincasar PFS)

J9370: Vincristine sulfate, 1 mg

√

96409

vinorelbine (Navelbine)

J9390: Injection, vinorelbine tartrate, per 10 mg

vorinostat (Zolinza)

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

zidovudine (Retrovir)

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

√

N/A

zidovudine (Retrovir)

S0104: Zidovudine, oral, 100 mg

√

N/A

ONCOLOGY PRACTICE MANAGEMENT

I December 2013

√

N/A

√

96409

Drug Coding

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

Please note: Check with payer regarding correct placement of medication information.

References HCPCS Level II Expert 2013 • Current Procedural Terminology (CPT ®) 2013 (copyright 2013 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association) • ICD-9-CM for Professionals Volumes 1 & 2, 2013 • FDA-approved indication (from product Prescribing Information) • Compendia references available upon request • www.

ReimbursementCodes.com powered by RJ Health Systems International, LLC, Rocky Hill, Connecticut • CMS (Centers for Medicare & Medicaid Services) CPT ® indicates Current Procedural Terminology; HCPCS, Healthcare Common Procedure Coding System: OPPS, outpatient prospective payment system

This information was supplied by:

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

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register today 4th annual conference

May 6-9, 2014 loews hollywood hotel • los angeles, ca

www.avbcconline.org

December 2013

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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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Clinical Trial Tracker

Clinical Trials Underway for Pediatric, Adolescent, and Young Adult Patients with Cancer

T

he following clinical trials are currently recruiting pediatric, adolescent, and young adult patients with cancer for inclusion in several investigations targeting blood and brain cancers in this population.

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

1

Autologous T-Lymphocytes Genetically Targeted to the B-Cell Specific Antigen CD19 in Patients with Relapsed B-Cell Acute Lymphoblastic Leukemia This phase 1 study will test the safety of giving pediatric and young adult patients with relapsed B-cell acute lymphoblastic leukemia special cells made from their own blood called “modified T-cells.” The goal of the study is to find a safe dose of these modified T-cells for patients whose leukemia has returned to the bone marrow.

To be eligible for infusion of modified T-cells during the treatment arm of this study, patients must be younger than 26 years of age and have a history of relapsed/refractory CD19-specific B-cell acute lymphoblastic leukemia involving the marrow. It is important for physicians to note that on this particular protocol, ≥25% blasts by morphology and/or flow cytometry constitute a bone marrow relapse. In addition, the patients must have experienced ≥2 relapses, with an early first marrow relapse after complete remission (CR) at <18 months. Additionally, an intermediate/late first marrow relapse (first CR >18 months from

first CR) with poor initial response (≥5% blasts by morphology and/or flow cytometry) following reinduction chemotherapy also constitutes a bone marrow relapse.

For additional inclusion and exclusion criteria, contact the principal investigator, Kevin Curran, MD, at 212-639-5836. The trial is being conducted at Memorial Sloan-Kettering Cancer Center, New York, New York.

The NLM Identifier is NCT01860937.

Source: ClinicalTrials.gov, October 17, 2013.

mine the maximum tolerated dose of GNKG168 in relapsed ALL and AML patients.

For inclusion into the study, pa­ tients must be ≥1 and ≤21 years of age when originally diagnosed with ALL or AML, and they must have previously histologically confirmed ALL or AML at their original diagnosis or previous relapse.

Additionally, the patients must be in complete remission with less than 5% blasts in the bone marrow.

The trial is being conducted by the Therapeutic Advances in Childhood Leukemia Consortium.

Contact Jeannette van der Giessen at 323-361-8725 for more information, including inclusion/exclusion criteria and study sites. The NLM Identifier is NCT01743807.

Source: ClinicalTrials.gov, October 17, 2013.

2

GNKG168 in Patients with Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia GNKG168, an investigational drug, is a Toll-like receptor (TLR) agonist, which is a novel approach to stimulating an effective anti­­ tumor immune response because they are able to stimulate both innate and adaptive immune responses. In this phase 1 trial, GNKG168 will be studied in patients with relapsed and refractory acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) who are younger than 21 years of age.

Patients in the study would be in morphologic remission but be positive for minimum residual disease.

There will be 2 strata: patients who have received hematopoietic stem cell transplant and patients who have not. GNKG168 will be administered as a 60-minute intravenous infusion. One 14-day cycle consists of a 5-day treatment period followed by a 9-day rest period, and patients will receive 2 cycles before evaluation. The primary objective of the study is to deter-

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Safety Study of CPX-351 in Children with Relapsed Acute Myeloid Leukemia (AML) In this phase 1 study of children and adolescents 1 to 30 years of age, a drug called CPX-351 will be tested in different doses to assess the drug’s pharmacokinetics, toxicity, and tolerability in pediatric and young adults with relapsed/refractory hematologic malignancies to see which dose is safer in the study population.

CPX-351 has not yet been approved by the US Food and Drug Administration; it has only been used in research studies. The drug is made up of 2 chemotherapy drugs that patients may have already received, cytarabine and daunorubicin, which are now packaged together. The drug has previously been Continued on page 52

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Clinical Trial Tracker

Clinical Trials Underway for Pediatric…Continued from page 51 tested in adults. Pediatric and young adult patients with blood cancers such as leukemia and lymphoma are being recruited for the study.

These patients must have already been treated with standard chemotherapy, but have disease that is still growing or has come back.

The subjects will receive a single course of CPX-351 administered on days 1, 3, and 5. The study will first be open to children in a dose-exploration phase, and then be available to an expanded cohort, which will be open to children and young adults once a tolerable dose has been determined.

Also in this study, researchers will collect blood samples for special pharmacokinetic studies that will measure how much CPX-351 remains in the body over time.

These studies require the collection of several blood samples before and after the participants are given the study drug.

The single-institution study is conducted at Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. Celator Pharmaceuticals, Inc is the study sponsor. For more information, including full inclusion/exclusion criteria, contact Laura Fossett, MS, at 513-636-2799. The NLM Iden­tifier is NCT01943682. Source: Clinical Trials.gov, October 17, 2013.

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Fixed versus Flexible Filgrastim to Accelerate Bone Marrow Re­­­­covery after Chemotherapy This randomized phase 3 trial will study the flexible administration of filgrastim after combination chemo­ therapy to see how well it works compared with the fixed administration of filgrastim in decreasing the side effects of chemotherapy in younger patients (1 to 25 years of age) with cancer.

Because filgrastim is customarily used on a fixed schedule starting

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early after initiation of chemotherapy and there are data that these early doses may not be needed, this study is testing a new flexible schedule of filgrastim with the goal to optimize its use by reducing the number of painful shots, the cost of treatment, and the drug’s side effects in children with cancer receiving chemotherapy.

The study is being conducted at the Barbara Ann Karmanos Cancer Institute, Detroit, MI, by the National Cancer Institute. For more information, including full inclusion and exclusion criteria, contact Maxim Y. Yankelevich at 313-745-5515 or myankele@med. wayne.edu. The NLM Identifier is NCT01987596. Source: Clinical Trials.gov, Novem­ber 26, 2013.

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Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients with Newly Diagnosed Diffuse Pontine Gliomas This phase 2/3 trial is studying the side effects and optimal dose of veliparib given together with radiation therapy and temozolomide to see how well it works in treating younger patients (21 years of age and younger) who are newly diagnosed with diffuse pontine gliomas.

Veliparib may stop the growth of tumor cells by blocking some of the enzymes that are needed for cell growth, and when used together with radiation therapy and chemotherapy, such as temozolomide, the drug may kill more tumor cells.

The study aims to identify the maximum tolerated dose or recommended phase 2 dose of veliparib that can be safely administered concurrently with radiation therapy, followed by maintenance therapy with veliparib and temozolomide. It will study the plasma pharmacokinetics of veliparib during combination veliparib and radiation therapy. It

ONCOLOGY PRACTICE MANAGEMENT

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will also study the feasibility of intrapatient dose escalation of temozolomide during maintenance therapy with veliparib and temozolomide.

For inclusion into the study, patients with newly diagnosed diffuse intrinsic pontine gliomas, which are defined as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons, are eligible without histologic confirmation.

Patients with brain stem tumors that do not meet these criteria or with brain stem tumors that are not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma. Patients with juvenile pilocytic astrocytoma, pilomyxoid astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible.

The study is being conducted by the National Cancer Institute.

Patricia A. Baxter, Texas Children’s Hospital, is the principal investigator. She can be contacted by e-mail at burton@bcm.edu. The study sites are in: Washington, DC; Chicago, IL; Bethesda, MD; Durham, NC; Philadelphia, PA; Pittsburgh, PA; Memphis, TN; and Houston, TX. The NLM Identifier is NCT01514201.

Source: Clinical Trials.gov, October 17, 2013.

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MK-1775 and Local Radiation Therapy in Treating Newly Diagnosed, Diffuse Intrinsic Pontine Gliomas This phase 1 trial is studying the side effects and best dose of MK-1775, a WEE1 inhibitor, when given together with local radiation therapy to treat pediatric and young adult patients (37 months to 21 years of age) with newly diagnosed, Continued on page 54

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Clinical Trial Tracker

Clinical Trials Underway for Pediatric…Continued from page 53 diffuse intrinsic pontine gliomas (DIPGs). MK-1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The trial will also define and describe the toxicities of MK-1775 when given concurrently with radiation therapy in children with newly diagnosed DIPGs. Patients with newly diagnosed DIPGs, which are defined as tumors with a pontine epicenter and diffuse involvement of the pons, are eligible without histologic confirmation.

Patients with brain stem tumors

that do not meet these criteria or are not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma, gliosarcoma, or anaplastic mixed glioma; patients with pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible.

The National Cancer Institute is conducting the study. Sabine Mueller, MD, PhD, assistant professor of neurology, pediatrics, and

neurosurgery at the University of California San Francisco School of Medicine, Department of Pediatrics, is the principal investigator. She can be contacted at 415-476-3831 or muellers@neuropeds.ucsf.edu.

The study sites are in: Arcadia, CA; Orange, CA; San Francisco, CA; Atlanta, GA; Indianapolis, IN; Minneapolis, MN; St. Louis, MO; Cincinnati, OH; Pittsburgh, PA; and Memphis, TN. The NLM Identifier is NCT01922076. Source: ClinicalTrials.gov, October 17, 2013. l

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Patient-Provider Access

The Government Shutdown May Have Long-Ranging Effects

By Sydney Abbott, JD Manager Provider, Economics and Public Policy, Association of Community Cancer Centers

S

ince the passage of the Budget Control Act, which was designed to control spending by capping defense and nondefense discretionary spending, there have been attempts to avoid the dramatic cuts established by the law to achieve certain spending targets.

Specifically, a bipartisian, bicameral committee was created in 2011 to find a balanced deficit reduction plan, which we now know did not happen and ultimately led to the sequester going into effect in 2013.

Sequestration impacts healthcare by cutting funding to the Centers for Medicare & Medicaid Services (CMS), the Centers for Disease Control and Prevention, the National Institutes of Health, and the Affordable Care Act programs. While each of these cuts impacts community oncology, this article addresses exclusively the 2% across-the-board reduction to Medicare reimbursement.

The 2% across-the-board Medicare sequester, which applies to everything billed to Medicare—including drugs—has been squeezing the oncology community since the CMS implemented it in April of 2013.

Shortly after the sequester began, the Association of Community Cancer Centers (ACCC) surveyed its membership across various sites of care and found that nearly 60% of the respondents reported being impacted by the reduction in reimbursement.

In October, when sequestration hit the 6-month mark, the ACCC conducted a follow-up survey of its membership to see how cancer programs were coping and whether the picture that had been painted at the start of the sequester still stood. The results of the follow-up survey highlight some

interesting points about how the sequester is still impacting community oncology care.

Two thirds of the survey respondents report being impacted by the sequester. Of those impacted, 84% are making adjustments to operating expenses, including reducing staff

yet made changes in the follow-up survey, 25% responded that they did not expect to make changes in the future, compared with the 14% who reported the same in the original survey.

This may be good news, in that it may be possible that more cancer programs are finding ways to adjust to these reimbursement reductions without making changes to patient care.

Taken together, the results of these 2 surveys show that more cancer facilities are being negatively impacted as a result of the sequester, and that the cuts have impacts far beyond Medicare patients—they extend to all patients with cancer, cancer center staffs, and supportive care programs. Additionally, these surveys show that many ACCC members are resourceful and are coming up with innovative solutions to continue to care for their patients.

However, providers are also at the end of their rope—community oncology care cannot be cut further and the sequester must be reversed to preserve patient access to the supportive care services that relieve barriers to care, increase value, and help to reduce long-term costs.

The ACCC continues to encourage Congress to protect patient access to care by protecting community cancer care reimbursement, and will continue to push for a reasonable solution to the Medicare sequester. As always, we will keep members up to date on changes to this important issue. l

Providers are at the end of their rope— community oncology care cannot be cut further. hours or not replacing staff when they resign. The follow-up survey results show that the fastest growing area seeing cuts is nonrevenue-generating programs, such as patient navigation services. Reducing these services hinders the quality of care for all patients with cancer because these programs help patients with financial issues, dietary requirements, cultural barriers, health literacy, and other needs. Because these programs assist all of the patients in a particular cancer program, it is not surprising that 75% of the respondents said that the sequester is impacting every single one of their patients, regardless of the fact that the 2% reduction in reimbursement is only applied to Medicare claims directly. This is an increase of 15% from the initial survey on this question, which indicates that some of the broader implications of sequestration are just now beginning to surface.

Interestingly, of those who had not

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ZYTIGA® (abiraterone acetate) Tablets Brief Summary of Prescribing Information.

INDICATIONS AND USAGE ZYTIGA is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.

CONTRAINDICATIONS Pregnancy: ZYTIGA can cause fetal harm when administered to a pregnant woman. ZYTIGA is not indicated for use in women. ZYTIGA is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss [see Use in Specific Populations].

WARNINGS AND PRECAUTIONS Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess: ZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1) in full Prescribing Information]. In the two randomized clinical trials, grade 3 to 4 hypertension occurred in 2% of patients, grade 3 to 4 hypokalemia in 4% of patients, and grade 3 to 4 edema in 1% of patients treated with ZYTIGA [see Adverse Reactions].

Co-administration of a corticosteroid suppresses adrenocorticotropic hormone (ACTH) drive, resulting in a reduction in the incidence and severity of these adverse reactions. Use caution when treating patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, e.g., those with heart failure, recent myocardial infarction or ventricular arrhythmia. Use ZYTIGA with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with left ventricular ejection fraction < 50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) was not established because these patients were excluded from these randomized clinical trials [see Clinical Studies (14) in full Prescribing Information]. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with ZYTIGA. Adrenocortical Insufficiency: Adrenal insufficiency occurred in the two randomized clinical studies in 0.5% of patients taking ZYTIGA and in 0.2% of patients taking placebo. Adrenocortical insufficiency was reported in patients receiving ZYTIGA in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of adrenocortical insufficiency, particularly if patients are withdrawn from prednisone, have prednisone dose reductions, or experience unusual stress. Symptoms and signs of adrenocortical insufficiency may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA. If clinically indicated, perform appropriate tests to confirm the diagnosis of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations [see Warnings and Precautions].

Hepatotoxicity: In the two randomized clinical trials, grade 3 or 4 ALT or AST increases (at least 5X ULN) were reported in 4% of patients who received ZYTIGA, typically during the first 3 months after starting treatment. Patients whose baseline ALT or AST were elevated were more likely to experience liver test elevation than those beginning with normal values. Treatment discontinuation due to liver enzyme increases occurred in 1% of patients taking ZYTIGA. No deaths clearly related to ZYTIGA were reported due to hepatotoxicity events.

Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced ZYTIGA dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the ULN, or the bilirubin rises above three times the ULN, interrupt ZYTIGA treatment and closely monitor liver function.

Re-treatment with ZYTIGA at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN [see Dosage and Administration (2.2) in full Prescribing Information].

The safety of ZYTIGA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown.

Increased ZYTIGA Exposures with Food: ZYTIGA must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state. The safety of these increased exposures when multiple doses of abiraterone acetate are taken with food has not been assessed [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

ZYTIGA® (abiraterone acetate) Tablets ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: • Hypertension, Hypokalemia, and Fluid Retention due to Mineralocorticoid Excess [see Warnings and Precautions].

• Adrenocortical Insufficiency [see Warnings and Precautions].

• Hepatotoxicity [see Warnings and Precautions].

• Increased ZYTIGA Exposures with Food [see Warnings and Precautions].

Clinical Trial Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Two randomized placebo-controlled, multicenter clinical trials enrolled patients who had metastatic castration-resistant prostate cancer who were using a gonadotropin-releasing hormone (GnRH) agonist or were previously treated with orchiectomy. In both Study 1 and Study 2 ZYTIGA was administered at a dose of 1,000 mg daily in combination with prednisone 5 mg twice daily in the active treatment arms. Placebo plus prednisone 5 mg twice daily was given to control patients.

The most common adverse drug reactions (≥10%) reported in the two randomized clinical trials that occurred more commonly (>2%) in the abiraterone acetate arm were fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.

The most common laboratory abnormalities (>20%) reported in the two randomized clinical trials that occurred more commonly (≥2%) in the abiraterone acetate arm were anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.

Study 1: Metastatic CRPC Following Chemotherapy: Study 1 enrolled 1195 patients with metastatic CRPC who had received prior docetaxel chemotherapy. Patients were not eligible if AST and/or ALT ≥ 2.5X ULN in the absence of liver metastases. Patients with liver metastases were excluded if AST and/or ALT > 5X ULN. Table 1 shows adverse reactions on the ZYTIGA arm in Study 1 that occurred with a ≥2% absolute increase in frequency compared to placebo or were events of special interest. The median duration of treatment with ZYTIGA was 8 months.

Table 1: Adverse Reactions due to ZYTIGA in Study 1 ZYTIGA with Placebo with Prednisone (N=791) Prednisone (N=394) System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Musculoskeletal and connective tissue disorders Joint swelling/discomfort2 29.5 4.2 23.4 4.1 Muscle discomfort3 26.2 3.0 23.1 2.3 General disorders 4 Edema 26.7 1.9 18.3 0.8 Vascular disorders Hot flush 19.0 0.3 16.8 0.3 Hypertension 8.5 1.3 6.9 0.3 Gastrointestinal disorders Diarrhea 17.6 0.6 13.5 1.3 Dyspepsia 6.1 0 3.3 0 Infections and infestations Urinary tract infection 11.5 2.1 7.1 0.5 Upper respiratory tract infection 5.4 0 2.5 0 Respiratory, thoracic and mediastinal disorders Cough 10.6 0 7.6 0 Renal and urinary disorders Urinary frequency 7.2 0.3 5.1 0.3 Nocturia 6.2 0 4.1 0 Injury, poisoning and procedural complications Fractures5 5.9 1.4 2.3 0 Cardiac disorders Arrhythmia6 7.2 1.1 4.6 1.0 Chest pain or chest 7 discomfort 3.8 0.5 2.8 0 Cardiac failure8 2.3 1.9 1.0 0.3 1 Adverse

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

ZYTIGA® (abiraterone acetate) Tablets

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4 Includes

1 Adverse

terms Edema, Edema peripheral, Pitting edema, and Generalized edema 5 Includes all fractures with the exception of pathological fracture 6 Includes terms Arrhythmia, Tachycardia, Atrial fibrillation, Supraventricular tachycardia, Atrial tachycardia, Ventricular tachycardia, Atrial flutter, Bradycardia, Atrioventricular block complete, Conduction disorder, and Bradyarrhythmia 7 Includes terms Angina pectoris, Chest pain, and Angina unstable.

Myocardial infarction or ischemia occurred more commonly in the placebo arm than in the ZYTIGA arm (1.3% vs. 1.1% respectively).

8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased Table 2 shows laboratory abnormalities of interest from Study 1. Grade 3-4 low serum phosphorus (7%) and low potassium (5%) occurred at a greater than or equal to 5% rate in the ZYTIGA arm.

Table 2: Laboratory Abnormalities of Interest in Study 1 Abiraterone (N=791) Placebo (N=394) Laboratory All Grades Grade 3-4 All Grades Grade 3-4 Abnormality (%) (%) (%) (%) Hypertriglyceridemia 62.5 0.4 53.0 0 High AST 30.6 2.1 36.3 1.5 Hypokalemia 28.3 5.3 19.8 1.0 Hypophosphatemia 23.8 7.2 15.7 5.8 High ALT 11.1 1.4 10.4 0.8 High Total Bilirubin 6.6 0.1 4.6 0 Study 2: Metastatic CRPC Prior to Chemotherapy Study 2 enrolled 1088 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy. Patients were ineligible if AST and/or ALT ≥ 2.5X ULN and patients were excluded if they had liver metastases.

Table 3 shows adverse reactions on the ZYTIGA arm in Study 2 that occurred with a ≥ 2% absolute increase in frequency compared to placebo.

The median duration of treatment with ZYTIGA was 13.8 months.

Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % General disorders Fatigue 39.1 2.2 34.3 1.7 Edema2 25.1 0.4 20.7 1.1 Pyrexia 8.7 0.6 5.9 0.2 Musculoskeletal and connective tissue disorders Joint swelling/ discomfort3 30.3 2.0 25.2 2.0 Groin pain 6.6 0.4 4.1 0.7 Gastrointestinal disorders Constipation 23.1 0.4 19.1 0.6 Diarrhea 21.6 0.9 17.8 0.9 Dyspepsia 11.1 0.0 5.0 0.2 Vascular disorders Hot flush 22.3 0.2 18.1 0.0 Hypertension 21.6 3.9 13.1 3.0 Respiratory, thoracic and mediastinal disorders Cough 17.3 0.0 13.5 0.2 Dyspnea 11.8 2.4 9.6 0.9 Psychiatric disorders Insomnia 13.5 0.2 11.3 0.0 Injury, poisoning and procedural complications Contusion 13.3 0.0 9.1 0.0 Falls 5.9 0.0 3.3 0.0 Infections and infestations Upper respiratory tract infection 12.7 0.0 8.0 0.0 Nasopharyngitis 10.7 0.0 8.1 0.0 Renal and urinary disorders Hematuria 10.3 1.3 5.6 0.6 Skin and subcutaneous tissue disorders Rash 8.1 0.0 3.7 0.0

2 Includes 3 Includes

events graded according to CTCAE version 3.0 terms Edema peripheral, Pitting edema, and Generalized edema terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness

Table 4 shows laboratory abnormalities that occurred in greater than 15% of patients, and more frequently (>5%) in the ZYTIGA arm compared to placebo in Study 2. Grade 3-4 lymphopenia (9%), hyperglycemia (7%) and high alanine aminotransferase (6%) occurred at a greater than 5% rate in the ZYTIGA arm.

Table 4: Laboratory Abnormalities in > 15% of Patients in the ZYTIGA Arm of Study 2 Abiraterone (N = 542) Placebo (N = 540) 1-4 Grade 3-4 Grade 1-4 Grade 3-4 Laboratory Abnormality Grade % % % % Hematology Lymphopenia 38.2 8.7 31.7 7.4 Chemistry Hyperglycemia1 56.6 6.5 50.9 5.2 High ALT 41.9 6.1 29.1 0.7 High AST 37.3 3.1 28.7 1.1 Hypernatremia 32.8 0.4 25.0 0.2 Hypokalemia 17.2 2.8 10.2 1.7 1Based on non-fasting blood draws Cardiovascular Adverse Reactions: In the combined data for studies 1 and 2, cardiac failure occurred more commonly in patients treated with ZYTIGA compared to patients on the placebo arm (2.1% versus 0.7%). Grade 3-4 cardiac failure occurred in 1.6% of patients taking ZYTIGA and led to 5 treatment discontinuations and 2 deaths. Grade 3-4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and one death due to cardiac failure in the placebo group.

In Study 1 and 2, the majority of arrhythmias were grade 1 or 2. There was one death associated with arrhythmia and one patient with sudden death in the ZYTIGA arms and no deaths in the placebo arms. There were 7 (0.5%) deaths due to cardiorespiratory arrest in the ZYTIGA arms and 3 (0.3%) deaths in the placebo arms. Myocardial ischemia or myocardial infarction led to death in 3 patients in the placebo arms and 2 deaths in the ZYTIGA arms.

DRUG INTERACTIONS Effects of Abiraterone on Drug Metabolizing Enzymes: ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug [see Clinical Pharmacology (12.3) in full Prescribing Information].

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

Drugs that Inhibit or Induce CYP3A4 Enzymes: Based on in vitro data, ZYTIGA is a substrate of CYP3A4. The effects of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) on the pharmacokinetics of abiraterone have not been evaluated, in vivo. Avoid or use with caution, strong inhibitors and inducers of CYP3A4 during ZYTIGA treatment [see Clinical Pharmacology (12.3) in full Prescribing Information].

USE IN SPECIFIC POPULATIONS Pregnancy: Pregnancy Category X [see Contraindications].: ZYTIGA can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no adequate and well-controlled studies with ZYTIGA in pregnant women and ZYTIGA is not indicated for use in women, it is important to know that maternal use of a CYP17 inhibitor could affect development of the fetus. Abiraterone acetate caused developmental toxicity in pregnant rats at exposures that were lower than in patients receiving the recommended dose. ZYTIGA is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with ZYTIGA.

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

In an embryo-fetal developmental toxicity study in rats, abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6-17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/ day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients.

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

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

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

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

No dosage adjustment is necessary for patients with baseline mild hepatic impairment. In patients with baseline moderate hepatic impairment (ChildPugh Class B), reduce the recommended dose of ZYTIGA to 250 mg once daily. If elevations in ALT or AST >5X ULN or total bilirubin >3X ULN occur in patients with baseline moderate hepatic impairment, discontinue ZYTIGA treatment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in full Prescribing Information].

The safety of ZYTIGA in patients with baseline severe hepatic impairment has not been studied. These patients should not receive ZYTIGA. For patients who develop hepatotoxicity during treatment, interruption of treatment and dosage adjustment may be required [see Dosage and Administration (2.2) in full Prescribing Information, Warnings and Precautions, and Clinical Pharmacology (12.3) in full Prescribing Information].

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

OVERDOSAGE There have been no reports of overdose of ZYTIGA during clinical studies.

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

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

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

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

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

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

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

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

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

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

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

Manufactured by: Patheon Inc. Mississauga, Canada Manufactured for: Janssen Biotech, Inc. Horsham, PA 19044 © Janssen Biotech, Inc. 2012 Revised: December 2012 2000005445 K08Z121174A

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

IMPORTANT SAFETY INFORMATION

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Contraindications ZYTIGA® (abiraterone acetate) is not indicated for use in women. ZYTIGA® can cause fetal harm (Pregnancy Category X) when administered to a pregnant woman and is contraindicated in women who are or may become pregnant.

Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in blood pressure, hypokalemia, or fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition.

Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure (in study 1) or NYHA Class II to IV heart failure (in study 2) because these patients were excluded from these randomized clinical trials. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly.

Adrenocortical Insufficiency (AI) AI was reported in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®.

Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.

Hepatotoxicity Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). Measure serum transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function.

Increased ZYTIGA® Exposures with Food ZYTIGA® must be taken on an empty stomach. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.

Adverse Reactions The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.

The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.

Drug Interactions ZYTIGA® is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. Avoid co-administration with CYP2D6 substrates that have a narrow therapeutic index. If an alternative cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate. In vitro, ZYTIGA® inhibits CYP2C8. There are no clinical data on its use with drugs that are substrates of CYP2C8. Patients should be monitored closely for signs of toxicity related to the CYP2C8 substrate if used concomitantly with abiraterone acetate.

Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. The effects of strong CYP3A4 inhibitors or inducers on the pharmacokinetics of abiraterone have not been evaluated, in vivo. Strong inhibitors and inducers of CYP3A4 should be avoided or used with caution during treatment with ZYTIGA®.

Use in Specific Populations Do not use ZYTIGA® in patients with baseline severe hepatic impairment (Child-Pugh Class C).

Please see Brief Summary of Prescribing Information on adjacent pages.

© Janssen Biotech, Inc. 2013

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Our goal is to make access to ZYTIGA®(abiraterone acetate) simple, convenient, and easy.

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Support for your patients:

• Rapid assessment of patient eligibility/coverage • Prior authorization support • Concise benefit summary • Identification of specialty pharmacy provider

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ACCESS TO ZYTIGA® SIMPLIFIED FOR YOU AND YOUR PATIENTS Also available online at janssenaccessone.com

Please see Important Safety Information on back, and Brief Summary of Prescribing Information on adjacent pages.

Patient insurance benefit investigation is provided as a service by TheraCom, LLC and The Lash Group, Inc., under contract for Janssen Biotech, Inc. In this regard, TheraCom, LLC, and The Lash Group, Inc., assist healthcare professionals in the determination of whether treatment could be covered by the applicable third-party payer based on coverage guidelines provided by the payer and patient information provided by the healthcare provider under appropriate authorization following the provider’s exclusive determination of medical necessity.

Importantly, insurance verification is the ultimate responsibility of the provider. Third-party reimbursement is affected by many factors. Therefore, TheraCom, LLC, The Lash Group, Inc., and Janssen Biotech make no representation or guarantee that full or partial insurance reimbursement or any other payment will be available. This information is provided as an information service only. While TheraCom, LLC, and The Lash Group, Inc., try to provide correct information, they and Janssen Biotech make no representations or warranties, expressed or implied, as to the accuracy of the information. In no event shall TheraCom, LLC, The Lash Group, Inc., or Janssen Biotech or its employees or agents be liable for any damages resulting from or relating to the services. All providers and other users of this information agree that they accept responsibility for the use of this service.

Janssen Biotech assumes no responsibility for, and does not guarantee the quality, scope, or availability of the services including but not limited to reimbursement support services, patient education, and other support services. Each provider, not Janssen Biotech, is responsible for the services they provide. These support services have no independent value to providers apart from the product and are included within the cost of the product. © Janssen Biotech, Inc. 2013

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