Urology Practice Management December 2014

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

DECEMBER 2014

www.UroPracticeManagement.com

New Practice Guideline for Systemic Therapy in Men with Metastatic Prostate Cancer

By Rosemary Frei, MSc

VOLUME 3 • NUMBER 6

Enzalutamide Improves Survival After ADT in Patients with CRPC

By Robert Osborne

Orlando, FL—Treatment with enzalutamide (Xtandi) after progression with androgen-deprivation therapy (ADT) led to a significant improvement in survival for men with metastatic castration-resistant prostate cancer (mCRPC), according to a new randomized trial reported at the 2014

American Urological Association annual meeting.

Patients randomized to placebo had a median radiographic progression-free survival (PFS; primary end point) of 3.9 months, whereas the median had not been reached in the enzalutamide Continued on page 20

Where Did My Data Go?

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

A

Ethan Basch, MD, MSc

new guideline for systemic therapy in men with metastatic castration-resistant prostate cancer (mCRPC) is based on a literature review of recent publications and outlines the survival and quality-of-life benefits/toxicity effects of each recommendation (Basch Continued on page 11

T

here is no denying the trend of medical oncology practices being acquired by hospitals, whether through professional service agreements, employer–employee agreements, or something in between. The 2013 Community Oncology Practice Impact Report1—published by the Community

Oncology Alliance— shows that in the past 6 years, 469 (35%) of 1338 responding practices have been acquired, and the rate of acquisition has increased 20% in the 15 months since the 2012 report.

Across the country, educational sesContinued on page 14

ES r: C e UR blower SO istle loy E R Wh mp 6

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M ta t’ Do HU attle Wha to © 2014 Engage Healthcare Communications, LLC

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

Call for Papers

Do you have a practice management story to share

?

In your background as a urology practice manager, it’s likely there’s one business experience—and maybe more—that practice managers across the nation would want to read about.

High-interest topics include: the solution you found to a practice management challenge, reimbursement, your experience with EMR, Medicare audits, a memorable encounter that shaped the way you now run your business and/or practice medicine, or how you successfully integrated ancillary products and services into your practice as a revenue generator.

Send us your ideas!

Submit a 600- to 1500-word original article to Urology Practice Management that your fellow practice managers will want to read.

Submit to: info@the-lynx-group.com UPM_73114

In mCRPC therapy…

Is there more to the story?

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

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

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

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

Increased ZYTIGA® Exposures With Food—ZYTIGA® must be taken on an empty stomach. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken.

Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.

Adrenocortical Insufficiency (AI)—AI was reported in patients receiving ZYTIGA® in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA®. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.

Hypertension, Hypokalemia, and Fluid Retention Due to Mineralocorticoid Excess—Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in blood pressure, hypokalemia, or fluid retention. ZYTIGA® may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) because these patients were excluded from these randomized clinical trials.

Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly. mCRPC=metastatic castration-resistant prostate cancer; AST=aspartate aminotransferase; ALT=alanine aminotransferase.

Please see additional Important Safety Information on the next page.

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

For men with mCRPC who progressed on ADT

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

More than 1,000 days.

And every day tells a story.

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

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

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

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

IMPORTANT SAFETY INFORMATION (cont) Increased ZYTIGA® Exposures With Food—ZYTIGA® must be taken on an empty stomach. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken.

Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.

Hepatotoxicity—Monitor liver function and modify, withhold, or discontinue ZYTIGA® dosing as recommended (see Prescribing Information for more information). Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA®, every two weeks for the first three months of treatment, and monthly thereafter.

Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop.

Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA® treatment and closely monitor liver function. *Study Design: ZYTIGA®, in combination with prednisone, was evaluated in a phase 3, randomized, double-blind, placebo-controlled, multicenter trial in patients with mCRPC who had not received prior chemotherapy (N=1,088). Patients were using a luteinizing hormone-releasing hormone (LHRH) agonist or were previously treated with orchiectomy. In the ZYTIGA® arm, patients received ZYTIGA® 1,000 mg orally once daily + prednisone 5 mg orally twice daily. In the placebo arm, patients received placebo orally once daily + prednisone 5 mg orally twice daily. In this study, the co-primary efficacy end points were overall survival (OS) and radiographic progression-free survival.

ADT=androgen-deprivation therapy.

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

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

B:11.125 in

003307-130924

S:10.375 in

T:10.875 in

Drug Interactions—Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA® treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA® dosing frequency only during the co-administration period [see Dosage and Administration (2.3)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

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

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

Learn more today at

www.zytigahcp.com.

Every day tells a story.

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

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

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

WARNINGS AND PRECAUTIONS Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess: ZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1) in full Prescribing Information].

In the two randomized clinical trials, grade 3 to 4 hypertension occurred in 2% of patients, grade 3 to 4 hypokalemia in 4% of patients, and grade 3 to 4 edema in 1% of patients treated with ZYTIGA [see Adverse Reactions].

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

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

Measure serum transaminases (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced ZYTIGA dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop.

Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the ULN, or the bilirubin rises above three times the ULN, interrupt ZYTIGA treatment and closely monitor liver function.

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

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

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

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

• Adrenocortical Insufficiency [see Warnings and Precautions].

• Hepatotoxicity [see Warnings and Precautions].

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

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

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

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

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

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

Table 1: Adverse Reactions due to ZYTIGA in Study 1 ZYTIGA with Placebo with Prednisone (N=791) Prednisone (N=394) System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Musculoskeletal and connective tissue disorders Joint swelling/ discomfort2 29.5 4.2 23.4 4.1 Muscle discomfort3 26.2 3.0 23.1 2.3 General disorders Edema4 26.7 1.9 18.3 0.8 Vascular disorders Hot flush 19.0 0.3 16.8 0.3 Hypertension 8.5 1.3 6.9 0.3 Gastrointestinal disorders Diarrhea 17.6 0.6 13.5 1.3 Dyspepsia 6.1 0 3.3 0 Infections and infestations Urinary tract infection 11.5 2.1 7.1 0.5 Upper respiratory tract infection 5.4 0 2.5 0 Respiratory, thoracic and mediastinal disorders Cough 10.6 0 7.6 0 Renal and urinary disorders Urinary frequency 7.2 0.3 5.1 0.3 Nocturia 6.2 0 4.1 0 Injury, poisoning and procedural complications Fractures5 5.9 1.4 2.3 0 Cardiac disorders Arrhythmia6 7.2 1.1 4.6 1.0 Chest pain or chest discomfort7 3.8 0.5 2.8 0 Cardiac failure8 2.3 1.9 1.0 0.3

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

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

Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 (continued) ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) System/Organ Class All Grades1 Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Renal and urinary disorders Hematuria 10.3 1.3 5.6 0.6 Skin and subcutaneous tissue disorders Rash 8.1 0.0 3.7 0.0 1 Adverse events graded according to CTCAE version 3.0 2 Includes terms Edema peripheral, Pitting edema, and Generalized edema 3 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness

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

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

8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased 4 Includes

Table 2 shows laboratory abnormalities of interest from Study 1. Grade 3-4 low serum phosphorus (7%) and low potassium (5%) occurred at a greater than or equal to 5% rate in the ZYTIGA arm.

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

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

The median duration of treatment with ZYTIGA was 13.8 months.

Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) 1 System/Organ Class All Grades Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % General disorders Fatigue 39.1 2.2 34.3 1.7 Edema2 25.1 0.4 20.7 1.1 Pyrexia 8.7 0.6 5.9 0.2 Musculoskeletal and connective tissue disorders Joint swelling/ discomfort3 30.3 2.0 25.2 2.0 Groin pain 6.6 0.4 4.1 0.7 Gastrointestinal disorders Constipation 23.1 0.4 19.1 0.6 Diarrhea 21.6 0.9 17.8 0.9 Dyspepsia 11.1 0.0 5.0 0.2 Vascular disorders Hot flush 22.3 0.2 18.1 0.0 Hypertension 21.6 3.9 13.1 3.0 Respiratory, thoracic and mediastinal disorders Cough 17.3 0.0 13.5 0.2 Dyspnea 11.8 2.4 9.6 0.9 Psychiatric disorders Insomnia 13.5 0.2 11.3 0.0 Injury, poisoning and procedural complications Contusion 13.3 0.0 9.1 0.0 Falls 5.9 0.0 3.3 0.0 Infections and infestations Upper respiratory tract infection 12.7 0.0 8.0 0.0 Nasopharyngitis 10.7 0.0 8.1 0.0

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

Table 4: Laboratory Abnormalities in >15% of Patients in the ZYTIGA Arm of Study 2 Abiraterone (N=542) Placebo (N=540) Laboratory Grade 1-4 Grade 3-4 Grade 1-4 Grade 3-4 Abnormality % % % % Hematology Lymphopenia 38.2 8.7 31.7 7.4 Chemistry Hyperglycemia1 56.6 6.5 50.9 5.2 High ALT 41.9 6.1 29.1 0.7 High AST 37.3 3.1 28.7 1.1 Hypernatremia 32.8 0.4 25.0 0.2 Hypokalemia 17.2 2.8 10.2 1.7 1Based on non-fasting blood draws Cardiovascular Adverse Reactions: In the combined data for studies 1 and 2, cardiac failure occurred more commonly in patients treated with ZYTIGA compared to patients on the placebo arm (2.1% versus 0.7%).

Grade 3-4 cardiac failure occurred in 1.6% of patients taking ZYTIGA and led to 5 treatment discontinuations and 2 deaths. Grade 3-4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and one death due to cardiac failure in the placebo group.

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

Post Marketing Experience The following additional adverse reactions have been identified during post approval use of ZYTIGA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Respiratory, Thoracic and Mediastinal Disorders: non-infectious pneumonitis.

DRUG INTERACTIONS Drugs that Inhibit or Induce CYP3A4 Enzymes: Based on in vitro data, ZYTIGA is a substrate of CYP3A4.

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

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

Effects of Abiraterone on Drug Metabolizing Enzymes: ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine).

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

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

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

OVERDOSAGE Human experience of overdose with ZYTIGA is limited.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

In This Issue

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 Editorial Directors Dalia Buffery dbuffery@the-lynx-group.com Anne M. Cooper acooper@the-lynx-group.com

Associate Editor Lara J. Lorton Copyeditor Jessica Cheng Editorial Assistant Cara Guglielmon Production Manager Marie RS Borrelli The Lynx Group President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Human Resources Jennine Leale Associate Director, Content Strategy & Development John Welz Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistant Lora LaRocca Director, Digital Media Anthony Romano Jr Digital Media Specialist Charles Easton IV Web Content Manager Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Sangenito Senior Project Managers Alyson Bruni Jini Gopalaswamy Project Manager Deanna Martinez Project Coordinator Mike Kodada IT Manager Kashif Javaid Administrative Services Team Leader 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

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

FEATURES New Practice Guideline for Systemic Therapy in Men with Metastatic Prostate Cancer.......................................................... 1

By Rosemary Frei, MSc

Enzalutamide Improves Survival After ADT in Patients with CRPC...................................................................................................... 1

By Robert Osborne

Where Did My Data Go?............................................................................ 1

By Teri U. Guidi, MBA, FAAMA

Quality Care for Patients with Cancer ............................................... 12 Interview with Linda Bosserman, MD, FACP

Continued on page 10

MISSION STATEMENT Urology 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 urology patients deserve, providers must master the ever-changing business of urology. Urology Practice Management offers process solutions for members of the urology care team—medical, surgical, and radiation urologists, as well as executives, administrators, and coders/billers—to assist them in reimbursement, staffing, electronic health records, REMS, and compliance with state and federal regulations.

Urology Practice Management™, ISSN 2374-0752 (print); 2374-0760 (online), is published 6 times a year by Engage Healthcare Communications, LLC, 1249 South River Road, Cranbury, NJ 08512. Copyright © 2014 by Engage Healthcare Communications, LLC. All rights reserved. Urology Practice Management™ is a trademark of Engage Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or 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 Urology 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 Urology 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.

POSTMASTER: Correspondence regarding subscriptions or change of address should be directed to CIRCULATION DIRECTOR, Urology Practice Management™, 1249 South River Road, 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.

December 2014

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In This Issue

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

Continued from page 9

Patient Portals Improve Healthcare, but Are Still Works in Progress........................................................................................................................................ 21

By Chase Doyle

Disaster Planning for the Medical Office, Part 2.................................................................................. 22

By Mariana S-B Lamb, MS, with contributions from Richard Levine, MD

Ten Tips to Cut Your 2014 Taxes............................................................................................................... 24

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

Tattletale or Whistleblower: What’s an Employer to Do?................................................................... 26

By Robert D. Orzechowski, MBA, SPHR

2014 Election Is in the Books: What Will It Mean for Healthcare in 2015?........................................ 27

By Leah Ralph

EDITORIAL ADVISORY BOARD Neil Baum, MD Practicing Urologist New Orleans, LA Cheris Craig, MBA, CMPE Chief Administrative Officer Urology of Greater Atlanta, LLC Atlanta, GA Michael deWitt Clayton, MD, FACS Urology Associates of San Luis Obispo, CA

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UROLOGY PRACTICE MANAGEMENT

James A. Sylora, MD Urologist AUS–Midwest Urology Evergreen Park, IL

Jonathan Oppenheimer, MD, FCAP Medical Director, Chief Pathologist Oppenheimer Urologic Reference Laboratory Nashville, TN

Sean M. Weiss, CCP-P, CCA-P, ACS-EM, CPC, CPC-P Vice President & Chief Compliance Officer DecisionHealth/ Professional Services Gaithersburg, MD

Jonathan Rubenstein, MD Director of Coding and Compliance Chesapeake Urology Baltimore, MD

Rick Janss, MBA, CMPE Practice Administrator Clinical Urology Associates Gadsden, AL

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John McMann, MS Administrator Advanced Urology Specialists, LLC Oxford, FL

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December 2014

Prostate Cancer

New Practice Guideline for Systemic…Continued from the cover E, et al. J Clin Oncol. 2014 Sept 8.

Epub ahead of print).

Jointly issued by the American So­­ ciety of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO), the new guideline considers new systemic therapies for mCRPC, including abiraterone acetate (Zytiga), enzalutamide (Xtandi), and radium-223 (Xofigo).

“Something different about this guideline is that quality of life and toxicity have been elevated in the recommendations themselves—the patient experience is prioritized,” said lead investigator Ethan Basch, MD, MSc, Co-Chair of the ASCO/ CCO Expert Panel that developed the guideline, and Associate Professor of Medicine and Public Health, University of North Carolina at Chapel Hill. “In addition, the strength of the evidence and the strength of the recommendations are transparent.”

The new document builds on previous guidelines and a review of 25 new randomized controlled trials. According to the new recommendations: • Continuous androgen-deprivation therapy (ADT) via medication or surgery should be continued indefinitely, even if other therapies are added (benefit: moderate; harm: moderate; evidence: weak; recommendation: moderate) • Abiraterone acetate + prednisone, radium-223 in men with primarily bone metastases, or enzalutamide should be used in addition to ADT (all—benefit: moderate; harm: low; evidence: strong; recommendation: strong) • Docetaxel (Taxotere) + prednisone also should be used in

–– Antiandrogens, such as bicalu­ tamide (Casodex), flu­ tamide (Eulexin), or nilutamide (Nilandron) –– Ketoconazole –– Low-dose corticosteroid monotherapy • Bevacizumab (Avastin), estramustine (Emcyt), and sunitinib (Sutent) should not be used, because they do not increase survival or improve quality of life • Palliative care should be offered to all patients receiving any treatment, particularly those with symptoms or quality-of-life reduction.

“Our recommendation of early initiation of palliative care—which is distinct from end-of-life care—is an important part of the guideline,” Dr Basch said. “Palliative care is now looked at as beneficial and appropriate across this population, including for patients who may have a long time to live with metastatic cancer. Survival time with metastatic prostate cancer has increased with the availability of new drugs, and now it is recognized that we have to focus on support of the patients and their families and caregivers.”

He noted that cost and costeffectiveness were not taken into consideration in the recommendations, although cost was included in a table in the guideline and in the discussion. Dr Basch said it is important to have more postmarketing data to continue to ascertain the rate of serious adverse events in clinical practice. The team also did not recommend particular sequences or drug combinations, because of an insufficient evidence base for that, he said. l

“Something different about this guideline is that quality of life and toxicity have been elevated in the recommendations themselves—the patient experience is prioritized.”

—Ethan Basch, MD, MSc

addition to ADT (benefit: moderate; harm: moderate; evidence: strong; recommendation: moderate) • Other therapies to consider: –– Sipuleucel-T (Provenge) in asymp­tomatic or in minimally symptomatic men –– Cabazitaxel (Jevtana) and prednisone in men whose disease has progressed with docetaxel –– Mitoxantrone (Novantrone) + prednisone

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Interview with the Innovators

Quality Care for Patients with Cancer Interview with Linda Bosserman, MD, FACP, President, Wilshire Oncology Medical Group

T

he interview featured in this arti­ cle was conducted with Linda Bosserman, MD, FACP, at the 2014 conference of the Association for Value-Based Cancer Care.

Q: What are the main value-­ based concerns for oncologists in the United States?

Linda Bosserman (LB), MD, FACP: On­­cologists are very concerned that the treatments they give to patients are actually going to improve their health. As we learn more about the growing costs of cancer care and the burden of patient copayments, we’re looking at, “Do we really understand the full impact of the treatment we’re giving to patients?” That means the outcome as far as progression-free survival and overall survival, as well as toxicities, side effects, the costs of those, and the ­­costs to the patient of the overall regimen.

Q: Should oncologists concern themselves with cost issues, or is this beyond their clinical focus?

LB: In today’s environment, there is no way an oncologist can avoid understanding cost issues if we’re going to help our patients evaluate the regimens we’re recommending, the total treatment course, short-term and longterm toxicity, what the outcome is, and what their cost is going to be.

Q: Are you concerned with the level of copayment that is faced by many patients with cancer?

LB: As an active clinical oncologist and practice president [Wilshire Oncology Medical Group, Rancho Cucamonga, CA], I can tell you that patients’ copayments are a daily issue that our doctors, our staff, and I deal with. Particularly, even in senior advantage plans, patients are being

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UROLOGY PRACTICE MANAGEMENT

asked for 20% copayments on increasingly expensive regimens; for many this is unaffordable. It’s not just a chemotherapy, biologic therapy, or oral drug copayment. It’s copayments for visits and for multiple treatment courses that are really becoming unaffordable to patients. More and more of our patients are coming back and saying, “I can’t afford that regimen.

What are the alternatives? What are the costs?” We as physicians have had to learn it. Our staff has had to learn it.

In today’s environment, there is no way an oncologist can avoid understanding cost issues if we’re going to help our patients evaluate the regimens we’re recommending, the total treatment course, short-term and longterm toxicity, what the outcome is, and what their cost is going to be.

Q: What can and should be done to alleviate the cost burden on patients with cancer?

LB: When you look at the growing burden of individual patients paying for cancer care, we need to come together as payers, providers, the pharmaceutical industry, the

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December 2014

government, and ask, “Why do cancer patients have an unfair burden of copayments compared with other diseases, and what is a fair copayment for which treatments?” If we were an ideal world in a value-based system, we might have no copayments for things that were highly effective and increase cure, or markedly improve survival and quality of life. Perhaps as we got into further lines of treatment with lesser, even questionable benefit, there would be more responsibility on the part of the patient. There are many ideas out there, but we have to come up with a solution, because right now it’s becoming unaffordable for patients in America.

Q: There is a growing push toward involving patients in treatment decisions. Should this apply to oncology, or does the fact that cancer is often a life-and-death situation change the equation?

LB: As an oncologist who has practiced for 35 years, and in the ­ community where I really know my patients, when you listen to patients, you learn they want to be actively involved, they and their family, or a combination. Sometimes they appoint a family member, but they want to know the truth. They have marketing material, they go on the Internet, but they want to know from their doctor, “What is my health, what is my disease, what is the comprehensive treatment program, what can I expect from that short term and long term, and what will be my health outcome? Also, what is my copayment responsibility for this package?” In our practice, we have found it is essential that every patient who goes for individual chemotherapy teaching also has sepa-

Interview with the Innovators

rate financial teaching. People don’t understand their health plans. They don’t understand their copayment responsibilities. They need to have a plan, think about that with their families, and make arrangements, or, when available, apply for copayment assistance.

Q: Is there one theme that underlies patient care no matter where it is delivered in the United States?

LB: There’s one theme that ought to underlie everything we do.

We in medicine went into medicine to improve our patients’ health, to use our scientific knowledge, our years of training (12-14 years for an oncologist), to work with our patients, meet their needs, educate them, and walk with them through the path of their treatment, whether it’s for prevention, cure, or end of life, to improve their health, or relieve their suffering. We have to get back to that as the main value.

Q: There is continued concern regarding the consequences of community practices being absorbed into hospital settings. How does the setting in which care is offered impact the quality of care?

LB: We’re hearing a lot about this change in the care side for oncology patients. Traditionally, 85% of patients in the past 10 years in America have received most of their treatment in the community.

It was the largest side of clinical research, often with academic partnerships, and often using academic centers for super specialty, tertiary, or quaternary care. With the financial changes, we saw across the country a third of practices out of practice last year, and I believe this year will be even greater. It’s very regional. In Southern California, I’m not sure there will be many practitioners left within 2 years. They’re going to join academic centers, hospitals, or systems. In the big picture,

this could ideally become very beneficial to patients. If you look at the Kaiser system in California, which has 40% market share, it’s a completely integrated system. Between the pharmacy, medical benefits,

or C. Right now, consumers have no way to know if the care they’re getting is in their best interest and for their best outcome.

Q: What can physicians and practice managers do to boost awareness and participation in clinical trials?

LB: Our administration and team members promote clinical trials at the practice level. We also encourage patients to find out about clinical trials. In reality, the ClinicalTrials.gov website does not work well. I’ve done searches and tried to find active-treatment protocols for patients. It’s more complicated than patients can sort through themselves…then when you think you have active clinical trials, and you make phone calls, you find out that they’re not available. That system, as a core nationally, needs to be improved. As we educate patients about clinical trials, we find they’re very open to them, but they want the trial to be integrated into their health plan, into their treatment routine, and as close to home as possible. It’s a very important value to patients, but the system itself needs to be revamped, even though we’re making people aware of it at the practice level.

Linda Bosserman, MD, FACP

We all work as a team and try to divide the work to improve access, discussion, education, and treatment for our patients. No one doctor can do all this, and the team approach is critical.

Q: What tips would you share with members of the patient’s healthcare team—nurses, navigators, physician assistants, nurse practitioners—to facilitate access to care for their patients?

LB: Most of us, whether we’re in an academic or community practice, are working with a team approach: teams of medical oncologists, surgeons, radiation oncologists, plastic surgeons, and physical therapists, but also within our team in the practice. At the practice level we have secretaries who do intake, financial analysis, access, and authorization. We have medical assistants who enter data and talk to patients about medications

physicians, surgeons, oncologists, radiation oncologists, supportive care, rehabilitation, hospice, and survivorship, it’s all integrated on behalf of that patient. We’re seeing several systems come together in some regional markets to compete with each other. Ultimately, a patient could understand the health outcomes, survival rates, quality of life, and cost in system A versus B

December 2014

Continued on page 15

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Data Management

Where Did My Data Go? Continued from the cover sions at numerous oncology-focused society meetings and articles published in oncology-focused journals abound with topics on this subject.

The vast majority of these presentations and publications discuss issues such as why a practice should consider acquisition, how an agreement should be structured, how compensation can be calculated, and so forth. Only a few thus far have told the detailed story of what actually happens once the ink on an alignment deal has dried.

When any business owner sells to someone else, there will be significant changes for the previous owner as well as for staff. In the acquisition of a medical oncology practice, this is also true. Staff members will likely experience changes in compensation and performance expectations; physicians will cede some degree of control over daily operations; and payer and purchasing contracts will need to be changed. And, in all likelihood, data systems will change.

The typical medical oncology practice has numerous data systems for insurance verification, scheduling, electronic medical records (EMRs), drug inventory handling, clinical trials, billing, and overall practice management. It is rare that a hospital will simply adopt a practice’s systems.

Instead, new systems will be used, and with that comes a subtle change in control for physicians and practice managers who had been accustomed to having complete access to all of the detailed data residing in their various systems.

When a hospital takes over those systems and converts them to different data systems, what happens to the old data? Unfortunately, in the best cases, the historical data are accessible, but difficult to compare with new data. In the worst cases, much of the data are simply lost for good. Let’s explore some of the

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impact that a hospital acquisition can have on data.

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UROLOGY PRACTICE MANAGEMENT

The loss of a patient’s scheduling history can be frustrating, al­­though not disastrous, since the information likely also resides, albeit less conveniently organized, in the medical record. Similarly, losing built-in scheduling templates creates headaches for staff members who may have to recreate those in a new system. This is irritating, but not insurmountable.

2

Most practices today have EMRs; however, transferring data from one EMR to another can be very expensive if software interfaces must be purchased. Where interface is not possible, the transfer can be difficult, and there can be a nearly devastating impact: the information may have to be reentered into a new system. The time required to make this transfer is enormous, as staff members comb through the old system or through paper copies and painstakingly enter it into the new system. That time is compounded by what may be a steep learning curve for new software.

3

Since most acquisitions include moving a practice’s infusion business, including pharmacy, to a hospital’s domain, losing drug inventory data may not be a huge issue. Still, the hospital’s pharmacy systems often are not accessible to physicians, causing physicians to lose touch with their own utilization of various drugs. This, in turn, can thwart efforts to track adherence to guidelines or participation in quality programs like the Quality Oncology Practice Initiative (QOPI).

4

The loss of the above software system data (scheduling, EMRs, pharmacy) can prove calamitous for a clinical trials program. Data managers

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December 2014

may lose all of the data necessary to monitor and report adherence to protocol requirements for physical exams, test orders and results, and treatments delivered. Without this information, compensation from study sponsors could be withheld.

5

Losing historical billing data may not seem, at first glance, to be a concern; however, it may have an impact on physician compensation.

While a hospital cannot legally compensate physicians based directly on the infusion revenue that they generate, if the hospital’s staff are not properly trained and skilled in—and the billing system not designed for— the complexities associated with coding and billing for oncology services, revenue may suffer. That revenue is, at least in part, a source of funding for physician compensation and may affect physicians’ total income once an alignment agreement is implemented. In addition, the loss of historical billing data can also hamper efforts to track productivity.

6

Practice management systems are, in many ways, the backbone of a private practice; however, such systems do not generally exist in a hospital setting. Of particular concern is the lost ability to track all work relative value units (wRVUs).

In an office-based setting, there are wRVUs associated with technical charge codes for the administration of drugs of all kinds, such as hydrations, infusions, and injections. In a hospital setting, it is literally impossible to attribute specific technical services to any individual provider.

Therefore, physician productivity as measured by wRVUs will be lower when the infusion business transfers. In fact, data from the Oncology Management Consulting Group demonstrate an average wRVU differential of 17%. In other words,

Data Management

approximately 17% of a physician’s wRVUs come from the administration of treatments. This must be carefully examined prior to completing compensation packages that are based on wRVUs, particularly if benchmarked against external data.

The loss of historical data of any kind brings with it the loss of the ability to follow trends. Those trends may be as simple as tracking a patient’s no-show history, or they can be as highly complex and important as trending clinical and diagnostic data.

What, then, can a practice do to minimize the potentially catastrophic impact of a change in data systems?

Obviously, in the ideal world, all of a practice’s data would be uploaded in a perfect format to new systems. But complete transfer of all data is not usually possible.

Therefore, the practice should first be certain to retain access to its existing systems for a reasonable amount of time after a transition. This may result in unanticipated costs for software licenses, hardware, and technical support. Second, consider “printing” all data to electronic files that could be utilized in the dire event of a total loss of functioning software.

Software vendors may be able to do this, or the practice may need to

engage temporary staff—either way, this step will likely incur unanticipated costs.

Finally, for any practice staff members who will be transitioning to the new systems, ensure that the hospital provides adequate training and support, and that the hospital clearly recognizes that staff and physician productivity will be hampered by steep learning curves. l

Reference

1. Community Oncology Alliance. Community Oncology Practice Impact Report: The Changing Landscape of Cancer Care. www.communityoncology. org/pdfs/Community%20Oncology%20Practice%20 Impact%20Report%206-24-13F.pdf. Published June 25, 2013. Accessed November 3, 2014.

Quality Care for Patients…Continued from page 13 and their vital signs. We have nurses who deliver chemotherapy.

We have advanced practice practitioners, otherwise known as nurse practitioners, and physician assistants, the physicians themselves, and our administrators. We all work as a team and try to divide the work to

Q: What are the advantages of Commission on Cancer accreditation? What are the disadvantages of not being accredited?

LB: Accreditation is important as setting standards….Hospitals use the Commission on Cancer to certify their programs. It has certainly encouraged community hospitals to put resources toward the work, elevating the work of tumor boards, the documentation, educational outreach for the community, having special cancer screening days in the community and at academic centers. While I think it’s important, I don’t think patients pay much attention to the level of accreditation. As the money has dried up at the community hospitals, I have seen a significant cutback in their willingness to put up funding for the certification that no one’s requiring. Setting standards is wonderful, so we can all be on the page together and try to do our best as teams, but it also has to have realistic funding. l

improve access, discussion, education, and treatment for our patients.

No one doctor can do all this, and the team approach is critical. That’s often a challenge to explain to patients and make sure they’re comfortable with the whole team being there to meet their needs.

INTERVIEW HIGHLIGHTS • In the current healthcare environment, oncologists cannot avoid understanding patients’ cost concerns when evaluating recommended treatment regimens.

• For many patients, copayments for cancer treatments, including medicines and patient visits, are unaffordable.

• Patients and family members want to be actively involved in the treatment process; it is essential that every patient who receives chemotherapy teaching also receives financial teaching so he or she better understands the costs associated with his or her treatment.

• Recent trends indicate that community cancer centers will continue to merge with larger academic centers or hospitals, which may allow for more integrated systems of cancer care.

• Patients are interested in participating in clinical trials; however, they would like the trial to be integrated into their health plan and treatment routine, and to be close to their home.

• A team approach to cancer care is critical; it is important to explain this approach to patients and ensure they are comfortable with it.

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Your Patients, Your Practice…

Helping Your Practice This comprehensive financial assistance program offers ongoing support across the reimbursement spectrum to help you help your patients.

Complete Provider Assistance Benefits verification Prior authorization tracking Regionally dedicated case managers Local access and reimbursement specialists Denied claims assistance Indication XTANDI (enzalutamide) capsules is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Important Safety Information Contraindications XTANDI (enzalutamide) capsules can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant.

Warnings and Precautions In Study 1, conducted in patients with metastatic castration-resistant prostate cancer (CRPC) who previously received docetaxel, seizure occurred in 0.9% of patients who were treated with XTANDI and 0% treated with placebo. In Study 2, conducted in patients with chemotherapy-naïve metastatic CRPC, seizure occurred in 0.1% of patients who were treated with XTANDI and 0.1% treated with placebo. Patients experiencing a seizure were permanently discontinued from therapy and all seizure events resolved. There is no clinical trial experience re-administering XTANDI to patients who experienced a seizure, and limited clinical trial experience in patients with predisposing factors for seizure. Study 1 excluded the use of concomitant medications that may lower threshold, whereas Study 2 permitted the use of these medications.

Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity during which sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Adverse Reactions The most common adverse reactions (≥ 10%) reported from the two combined clinical trials that occurred more commonly (≥ 2% over placebo) in the XTANDI-treated patients were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/ vertigo.

Other Adverse Reactions include: • Laboratory Abnormalities: In the two studies, Grade 1-4 neutropenia occurred in 15% of patients treated with XTANDI (1% Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade 3-4). The incidence of Grade 1-4 thrombocytopenia was 6% of patients treated with XTANDI (0.3% Grade 3-4) and 5% of patients on placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of patients treated with XTANDI (0.2% Grade 3-4) and 16% of patients treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients treated with XTANDI

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

Medicare/Medicaid Referrals to Independent Copay Foundations†

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(0.1% Grade 3-4) and 2% of patients treated with placebo (no Grade 3-4).

• Infections: In Study 1, 1% of XTANDI versus 0.3% of placebo patients and in Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.

• Falls: In the two studies, falls including fall-related injuries occurred in 9% of XTANDI patients vs 4% treated with placebo. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients and included non-pathologic fractures, joint injuries, and hematomas.

• Hypertension: In the two studies, hypertension was reported in 11% of patients receiving XTANDI and 4% of patients receiving placebo. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of XTANDI or placebo treated patients.

Drug Interactions • Effect of Other Drugs on XTANDI – Administration of strong CYP2C8 inhibitors can increase the plasma exposure to XTANDI. Co-administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible.

If co-administration of XTANDI cannot be avoided,

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reduce the dose of XTANDI. Co-administration of XTANDI with strong or moderate CYP3A4 and CYP2C8 inducers may alter the plasma exposure of XTANDI and should be avoided if possible.

• Effect of XTANDI on Other Drugs – XTANDI is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. Avoid CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

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

XTANDI Support SolutionsSM, a component of Astellas Access ServicesSM 1-855-8XTANDI (1-855-898-2634); Fax 1-855-982-6341; XTANDISupportSolutions.com ©2014 Astellas Pharma US, Inc. All rights reserved. 076-0329-PM 9/14 Printed in USA XTANDI, Astellas, and the flying star logo are trademarks of Astellas Pharma, Inc.

XTANDI® (enzalutamide) capsules for oral use Initial U.S. Approval: 2012 BRIEF SUMMARY OF PRESCRIBING INFORMATION The following is a brief summary. Please see the package insert for full prescribing information.

INDICATIONS AND USAGE

Grade 3 and higher adverse reactions were reported among 47% of XTANDI-treated patients and 53% of placebo-treated patients. Discontinuations due to adverse events were reported for 16% of XTANDI-treated patients and 18% of placebo-treated patients. The most common adverse reaction leading to treatment discontinuation was seizure, which occurred in 0.9% of the XTANDI-treated patients compared to none (0%) of the placebo-treated patients. Table 1 shows adverse reactions reported in Study 1 that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm.

Table 1. Adverse Reactions in Study 1 (cont.)

Respiratory Disorders

Table 1. Adverse Reactions in Study 1

Seizure In Study 1, which enrolled patients who previously received docetaxel, 7 of 800 (0.9%) patients treated with XTANDI experienced a seizure and no patients treated with placebo experienced a seizure. Seizure occurred from 31 to 603 days after initiation of XTANDI. In Study 2, 1 of 871 (0.1%) chemotherapy-naive patients treated with XTANDI and 1 of 844 (0.1%) patients treated with placebo experienced a seizure. Patients experiencing seizure were permanently discontinued from therapy and all seizure events resolved. There is no clinical trial experience readministering XTANDI to patients who experienced seizure.

Limited safety data are available in patients with predisposing factors for seizure because these patients were generally excluded from the trials. These exclusion criteria included a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation. Study 1 excluded the use of concomitant medications that may lower the seizure threshold, whereas Study 2 permitted the use of these medications.

Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

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

Two randomized clinical trials enrolled patients with metastatic prostate cancer that has progressed on androgen deprivation therapy (GnRH therapy or bilateral orchiectomy), a disease setting that is also defined as metastatic CRPC. In both studies, patients received XTANDI 160 mg orally once daily in the active treatment arm or placebo in the control arm. All patients continued androgen deprivation therapy. Patients were allowed, but not required, to take glucocorticoids.

The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the XTANDI-treated patients from the two randomized clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo.

Study 1: Metastatic Castration-Resistant Prostate Cancer Following Chemotherapy Study 1 enrolled 1199 patients with metastatic CRPC who had previously received docetaxel. The median duration of treatment was 8.3 months with XTANDI and 3.0 months with placebo. During the trial, 48% of patients on the XTANDI arm and 46% of patients on the placebo arm received glucocorticoids.

0.1

1.3

0.3

26.4

5.3

24.3

4.0

Arthralgia 20.5 Musculoskeletal 15.0 Pain Muscular 9.8 Weakness Musculoskeletal 2.6 Stiffness Gastrointestinal Disorders

2.5

17.3

1.8

1.3

11.5

0.3

Table 2. Adverse Reactions in Study 2

1.5

6.8

1.8

0.3

0.3

0.0

21.8

1.1

17.5

0.3

Hot Flush

20.3

0.0

10.3

0.0

Hypertension

6.4

2.1

2.8

1.3

Grade 1-4a (%)

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

3.3

CTCAE v4 Includes asthenia and fatigue.

Includes dizziness and vertigo.

Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention. e Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis. f Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

Study 2: Chemotherapy-naive Metastatic CastrationResistant Prostate Cancer Study 2 enrolled 1717 patients with metastatic CRPC who had not received prior cytotoxic chemotherapy, of whom 1715 received at least one dose of study drug. The median duration of treatment was 17.5 months with XTANDI and 4.6 months with placebo. Grade 3-4 adverse reactions were reported in 44% of XTANDItreated patients and 37% of placebo-treated patients.

Discontinuations due to adverse events were reported for 6% of XTANDI-treated patients and 6% of placebo-treated patients. The most common adverse reaction leading to treatment discontinuation was fatigue/asthenia, which occurred in 1% of patients on each treatment arm. Table 2 includes adverse reactions reported in Study 2 that occurred at a ≥ 2% higher frequency in the XTANDI arm compared to the placebo arm.

XTANDI N = 800

XTANDI is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC).

Pregnancy XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss [see Use in Specific Populations (8.1)].

Epistaxis a b c d

General Disorders Asthenic Conditionsb Peripheral Edema

Placebo N = 399

Grade Grade Grade 3-4 1-4 3-4 (%) (%) (%)

50.6

9.0

44.4

9.3

15.4

1.0

13.3

0.8

Musculoskeletal And Connective Tissue Disorders Back Pain

Diarrhea Vascular Disorders

Nervous System Disorders Headache

12.1

0.9

5.5

0.0

Dizzinessc Spinal Cord Compression and Cauda Equina Syndrome Paresthesia Mental Impairment Disordersd Hypoesthesia

9.5

0.5

7.5

0.5

XTANDI N = 871 Grade 1-4a (%)

Grade 3-4 (%)

Placebo N = 844 Grade 1-4 (%)

Grade 3-4 (%)

General Disorders Asthenic 46.9 3.4 33.0 2.8 Conditionsb Peripheral 11.5 0.2 8.2 0.4 Edema Musculoskeletal And Connective Tissue Disorders Back Pain

28.6

2.5

22.4

3.0

Arthralgia

21.4

1.6

16.1

1.1

Gastrointestinal Disorders 7.4

6.6

4.5

3.8

6.6

0.0

4.5

0.0

4.3

0.3

1.8

0.0

4.0

0.3

1.8

0.0

0.0

6.5

0.3

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

2.4

4.8

1.3

Insomnia

8.8

0.0

6.0

0.5

Anxiety

6.5

0.3

4.0

0.0

Renal And Urinary Disorders Hematuria

6.9

1.8

4.5

1.0

Pollakiuria

4.8

0.0

2.5

0.0

Injury, Poisoning And Procedural Complications Fall 4.6 0.3 1.3 Non-pathologic 4.0 1.4 0.8 Fractures Skin And Subcutaneous Tissue Disorders

0.0 0.3

Pruritus

3.8

0.0

1.3

0.0

Dry Skin

3.5

0.0

1.3

0.0

Constipation

23.2

0.7

17.3

0.4

Diarrhea

16.8

0.3

14.3

0.4

Vascular Disorders Hot Flush

18.0

0.1

7.8

0.0

Hypertension

14.2

7.2

4.1

2.3

Nervous System Disorders Dizzinessc

11.3

0.3

7.1

0.0

Headache

11.0

0.2

7.0

0.4

Dysgeusia

7.6

0.1

3.7

0.0

5.7

0.0

1.3

0.1

2.1

0.1

0.4

0.0

0.6

8.5

0.6

10.5

0.0

4.7

1.1

5.7

0.0

Mental Impairment Disordersd Restless Legs Syndrome

Respiratory Disorders Dyspneae

11.0

Infections And Infestations Upper Respiratory 16.4 0.0 Tract Infectionf Lower Respiratory Tract And 7.9 1.5 Lung g Infection Psychiatric Disorders Insomnia

8.2

0.1

Table 2. Adverse Reactions in Study 2 (cont.)

Renal And Urinary Disorders Hematuria

8.8

1.3

5.8

1.3

Injury, Poisoning And Procedural Complications Fall

12.7

1.6

5.3

NonPathological 8.8 2.1 3.0 Fracture Metabolism and Nutrition Disorders Decreased 18.9 0.3 16.4 Appetite

0.7 1.1

0.7

Investigations Weight Decreased

12.4

0.8

8.5

0.2

Reproductive System and Breast Disorders Gynecomastia

3.4

0.0

1.4

0.0

a b c d

CTCAE v4 Includes asthenia and fatigue.

Includes dizziness and vertigo.

Includes amnesia, memory impairment, cognitive disorder, and disturbance in attention. e Includes dyspnea, exertional dyspnea, and dyspnea at rest. f Includes nasopharyngitis, upper respiratory tract infection, sinusitis, rhinitis, pharyngitis, and laryngitis. g Includes pneumonia, lower respiratory tract infection, bronchitis, and lung infection.

Laboratory Abnormalities In the two randomized clinical trials, Grade 1-4 neutropenia occurred in 15% of patients treated with XTANDI (1% Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade 3-4).

The incidence of Grade 1-4 thrombocytopenia was 6% of patients treated with XTANDI (0.3% Grade 3-4) and 5% of patients treated with placebo (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of patients treated with XTANDI (0.2% Grade 3-4) and 16% of patients treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of patients treated with XTANDI (0.1% Grade 3-4) and 2% of patients treated with placebo (no Grade 3-4).

Infections In Study 1, 1% of patients treated with XTANDI compared to 0.3% of patients treated with placebo died from infections or sepsis. In Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.

Falls and Fall-related Injuries In the two randomized clinical trials, falls including fall-related injuries, occurred in 9% of patients treated with XTANDI compared to 4% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in patients treated with XTANDI and included non-pathologic fractures, joint injuries, and hematomas.

Hypertension In the two randomized trials, hypertension was reported in 11% of patients receiving XTANDI and 4% of patients receiving placebo. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of patients in each arm.

DRUG INTERACTIONS Drugs that Inhibit or Induce CYP2C8 Co-administration of a strong CYP2C8 inhibitor (gemfibrozil) increased the composite area under the plasma concentration-time curve (AUC) of enzalutamide plus N-desmethyl enzalutamide by 2.2-fold in healthy volunteers. Co-administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If co-administration of XTANDI with a strong CYP2C8 inhibitor cannot be avoided, reduce the dose of XTANDI [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

The effects of CYP2C8 inducers on the pharmacokinetics of enzalutamide have not been evaluated in vivo.

Co-administration of XTANDI with strong or moderate CYP2C8 inducers (e.g., rifampin) may alter the plasma exposure of XTANDI and should be avoided if possible.

Selection of a concomitant medication with no or minimal CYP2C8 induction potential is recommended [see Clinical Pharmacology (12.3)].

Drugs that Inhibit or Induce CYP3A4 Co-administration of a strong CYP3A4 inhibitor (itraconazole) increased the composite AUC of enzalutamide plus N-desmethyl

enzalutamide by 1.3-fold in healthy volunteers [see Clinical Pharmacology (12.3)].

The effects of CYP3A4 inducers on the pharmacokinetics of enzalutamide have not been evaluated in vivo.

Co-administration of XTANDI with strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine) may decrease the plasma exposure of XTANDI and should be avoided if possible.

Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) and St. John’s Wort may also reduce the plasma exposure of XTANDI and should be avoided if possible [see Clinical Pharmacology (12.3)].

Effect of XTANDI on Drug Metabolizing Enzymes Enzalutamide is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. At steady state, XTANDI reduced the plasma exposure to midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate). Concomitant use of XTANDI with narrow therapeutic index drugs that are metabolized by CYP3A4 (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus), CYP2C9 (e.g., phenytoin, warfarin) and CYP2C19 (e.g., S-mephenytoin) should be avoided, as enzalutamide may decrease their exposure. If co-administration with warfarin cannot be avoided, conduct additional INR monitoring [see Clinical Pharmacology (12.3)].

USE IN SPECIFIC POPULATIONS Pregnancy - Pregnancy Category X [see Contraindications (4)].

Risk Summary XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no human data on the use of XTANDI in pregnancy and XTANDI is not indicated for use in women, it is important to know that maternal use of an androgen receptor inhibitor could affect development of the fetus. Enzalutamide caused embryofetal toxicity in mice at exposures that were lower than in patients receiving the recommended dose. XTANDI is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with XTANDI. Animal Data In an embryo-fetal developmental toxicity study in mice, enzalutamide caused developmental toxicity when administered at oral doses of 10 or 30 mg/kg/day throughout the period of organogenesis (gestational days 6-15). Findings included embryo-fetal lethality (increased post-implantation loss and resorptions) and decreased anogenital distance at ≥ 10 mg/kg/day, and cleft palate and absent palatine bone at 30 mg/kg/day. Doses of 30 mg/kg/day caused maternal toxicity. The doses tested in mice (1, 10 and 30 mg/kg/day) resulted in systemic exposures (AUC) approximately 0.04, 0.4 and 1.1 times, respectively, the exposures in patients. Enzalutamide did not cause developmental toxicity in rabbits when administered throughout the period of organogenesis (gestational days 6-18) at dose levels up to 10 mg/kg/day (approximately 0.4 times the exposures in patients based on AUC).

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

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

Geriatric Use Of 1671 patients who received XTANDI in the two randomized clinical trials, 75% were 65 and over, while 31% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients. Other reported clinical

experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients with Renal Impairment A dedicated renal impairment trial for XTANDI has not been conducted.

Based on the population pharmacokinetic analysis using data from clinical trials in patients with metastatic CRPC and healthy volunteers, no significant difference in enzalutamide clearance was observed in patients with pre-existing mild to moderate renal impairment (30 mL/min ≤ creatinine clearance [CrCL] ≤ 89 mL/min) compared to patients and volunteers with baseline normal renal function (CrCL ≥ 90 mL/min). No initial dosage adjustment is necessary for patients with mild to moderate renal impairment. Severe renal impairment (CrCL < 30 mL/min) and end-stage renal disease have not been assessed [see Clinical Pharmacology (12.3)].

Patients with Hepatic Impairment A dedicated hepatic impairment trial compared the composite systemic exposure of enzalutamide plus N-desmethyl enzalutamide in volunteers with baseline mild or moderate hepatic impairment (Child-Pugh Class A and B, respectively) versus healthy controls with normal hepatic function.

The composite AUC of enzalutamide plus N-desmethyl enzalutamide was similar in volunteers with mild or moderate baseline hepatic impairment compared to volunteers with normal hepatic function. No initial dosage adjustment is necessary for patients with baseline mild or moderate hepatic impairment. Baseline severe hepatic impairment (Child-Pugh Class C) has not been assessed [see Clinical Pharmacology (12.3)].

OVERDOSAGE In the event of an overdose, stop treatment with XTANDI and initiate general supportive measures taking into consideration the half-life of 5.8 days. In a dose escalation study, no seizures were reported at < 240 mg daily, whereas 3 seizures were reported, 1 each at 360 mg, 480 mg, and 600 mg daily. Patients may be at increased risk of seizure following an overdose.

NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been conducted to evaluate the carcinogenic potential of enzalutamide.

Enzalutamide did not induce mutations in the bacterial reverse mutation (Ames) assay and was not genotoxic in either the in vitro mouse lymphoma thymidine kinase (Tk) gene mutation assay or the in vivo mouse micronucleus assay.

Based on nonclinical findings in repeat-dose toxicology studies, which were consistent with the pharmacological activity of enzalutamide, male fertility may be impaired by treatment with XTANDI. In a 26-week study in rats, atrophy of the prostate and seminal vesicles was observed at ≥ 30 mg/kg/day (equal to the human exposure based on AUC). In 4-, 13-, and 39-week studies in dogs, hypospermatogenesis and atrophy of the prostate and epididymides were observed at ≥ 4 mg/kg/day (0.3 times the human exposure based on AUC).

Manufactured by: Catalent Pharma Solutions, LLC, St. Petersburg, FL 33716 Manufactured for and Distributed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Marketed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Medivation, Inc., San Francisco, CA 94105 Revised: September 2014 14B006-XTA-BRFS Rx Only © 2014 Astellas Pharma US, Inc. XTANDI® is a registered trademark of Astellas Pharma Inc.

076-0472-PM

Prostate Cancer

Enzalutamide Improves Survival After ADT…Continued from the cover group, said Christopher P. Evans, MD, Chair, Department of Urology, University of California, Davis, Sacramento.

“In both the intention-to-treat population, and in the subgroup of patients with nonvisceral disease, treatment with enzalutamide significantly delayed the progression of metastatic disease, reduced the risk of death, and delayed the time to ini­

Phase 3 Clinical Trial: PREVAIL The data came from the multicenter international phase 3 clinical trial PREVAIL involving 1717 patients with mCRPC who had progressed with ADT but who had not yet received chemotherapy.

The inclusion criteria limited enrollment to patients who were asymptomatic or who had only mild

“Treatment with enzalutamide significantly delayed the progression of metastatic disease, reduced the risk of death, and delayed the time to initiation of cytotoxic chemotherapy.”

—Christopher P. Evans MD

20

tiation of cytotoxic chemotherapy,” said Dr Evans. “Consistent benefits also were seen in the visceraldisease group.”

“Enzalutamide added to androgen-deprivation therapy at progression provides meaningful clinical benefit to men with metastatic castration-resistant prostate cancer,” he added.

Enzalutamide disrupts androgen signaling by affecting 3 activities involving the androgen receptor: the drug inhibits binding of androgens to the androgen receptor, inhibits androgen receptor nuclear translocation, and inhibits androgen receptor–mediated DNA binding. In the postdocetaxel setting, enzalutamide treatment resulted in improved survival and radiographic PFS (Scher HI, et al. N Engl J Med. 2012;367:1187-1197).

symptoms. Patients continued ADT and were randomized to enzalutamide 160 mg daily or to placebo.

The coprimary end points were radiographic PFS and overall survival (OS).

A final OS analysis was planned to take place after 765 events had occurred, but the trial ended prematurely after a planned interim analysis demonstrated significant advantages in the coprimary end points in favor of enzalutamide.

The total patient population included 204 patients with visceral involvement. The median age was approximately 71 years, and approximately 50% of patients had a Gleason score of ≥8 at diagnosis; almost 90% had previous antiandrogen exposures, and approximately 25% had undergone radical prostatectomy.

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UROLOGY PRACTICE MANAGEMENT

December 2014

Overall, approximately 80% of the patients had bone metastases, and more than 50% had soft-tissue disease.

The median treatment duration was almost 17 months in the enzalutamide arm versus 4.7 months in the placebo group (P = .001), and the magnitude of benefit was similar in patients with and without visceral involvement. Treatment duration in the subgroup with visceral disease was 14 months with enzalutamide and 3.7 months with placebo. Almost 70% of patients in the enzalutamide arm completed at least 12 months of treatment, said Dr Evans.

At the interim analysis, the median OS was 32.4 months (upper confidence interval not yet reached) with enzalutamide and 30.2 months with placebo, representing a 30% reduction in the hazard ratio (HR; P <.001). Patients without visceral disease also had significant improvement in OS (not yet reached vs 30.2 months with placebo; HR, 0.692; P = .001). In the patients with visceral involvement, OS at the interim analysis favored enzalutamide (27.8 vs 22.8 months), but the upper limit of the confidence intervals had yet to be reached in either treatment arm.

Enzalutamide more than doubled the time to chemotherapy versus placebo (28 vs 10.8 months, respectively; HR, 0.349; P <.001), al­­ though that analysis is ongoing.

Enzalutamide was associated with slightly more adverse events (AEs), including serious events (31.6% vs 26.2%, respectively) and grade ≥3 (42.3% vs 37.3%, respectively).

The time to a first grade ≥3 AE was prolonged in the enzalutamide arm versus placebo (22.7 vs 13.7 months, respectively), and discontinuation related to AEs and fatal AEs occurred in a similar proportion of patients in each group. l

Patient Portals

Patient Portals Improve Healthcare, but Are Still Works in Progress

By Chase Doyle

San Diego, CA—Patient portals offer valuable benefits to providers and patients by enhancing patient– provider communication, increasing operational efficiencies, and empowering patients, according to data presented at the 2014 Association of Community Cancer Centers National Oncology Conference.

“Patients report a sense of auton­ omy when they are given digitized access to their medical records,” said Cary A. Presant, MD, of Wilshire Oncology-US Oncology, who is Professor of Clinical Medicine, University of Southern California School of Medicine, Los Angeles. “By giving patients the metrics to monitor their own disease so they know to look for tumor markers, for example, or look for blood pressure, [they can] see how they’re actually doing.”

Although in existence since 2002, the use of patient portals has been rising because of the Health In­ formation Technology for Economic and Clinical Health (HITECH) Act, an increase in electronic medical record (EMR) incentive payments starting in 2011, and the threat of reduced payment for lack of EMR use in 2015.

“Portals exist because digitization is universal,” said Dr Presant, “but we [healthcare professionals] have been among the last professions to get into digitization.” The recent push, however, has not come solely from legislative pressure or financial incentives. Rather, portals exist, in large part, as a result of patient preferences.

“We have lots of patients who truly prefer digitized types of interactions; they also realize the inefficiencies in our offices that have existed in the past and the fact that having their

own portal may reduce this kind of frustration,” Dr Presant said.

In a survey of 13,564 patients and 105 physicians, 82% of patients said they felt more in control and 99% of patients wanted OpenNotes to continue (Delbanco T, et al. Ann Intern Med. 2012;157:461-470). The results, however, were not entirely positive.

Of physicians, 19% changed their documentation on account of patient viewership and 11% spent more time writing their notes, indicating a need for portals to become more efficient in the future.

Whether portals can influence outcome also remains to be seen.

Fourteen randomized controlled trials revealed insufficient evidence that patient portals improve health outcomes or cost (Goldzweig CL, et al. Ann Intern Med. 2013;159:677687). A separate study of the impact of portals on care delivery actually showed an increase in the number of emergency department and physician office visits by patients (Bates DW, et al. JAMA. 2012;308:20342036). In a 1000-patient practice, the use of portals resulted in 10 more patient visits per week, 5.5 additional phone calls per week, and increased workload for doctors. Yet, the appeal of direct and open informational exchange between patients and providers is undeniable.

“Educational materials are the real gift of patient portals,” said Kim Woofter, RN, OCN, Chief Operat­ ing Officer at Michiana Hematology Oncology in northern Indiana. “I have the ability not just to share lab results in real-time but to link to websites and reliable resources…[so that] patients feel like they’re in control.”

Another selling point for Ms Woofter is the appointment calen-

December 2014

dar—anything scheduled in-house or at an outside facility is uploaded to a real-time calendar—and for patients who travel, the ability to upload personal health records makes for ­ smoother transitions between treatment facilities. However, such immediate and shared access is not without its complications.

“In the beginning, physicians were not happy with the thought of all lab results going directly to a patient in real-time,” said Ms Woofter, who has implemented a 4-day delay on tumor markers to allow physicians to contact their patients first.

Despite the obvious benefits, registration remains an ongoing challenge for Ms Woofter, with only 40% of new patients adopting portals. The biggest incentive is family—the ability to share the treatment process with relatives eager to get involved. But if that does not work, there are free iPads, gifted with random drawings to 1 registered patient monthly.

Clearly, patient portals are not perfect: there are user errors, crashes, and malfunctions, and there is a greater risk of malpractice as a result of in­­ creased availability of information, as well as the possibility that a patient will not like the information. Dr Presant even cites the potential for a computer virus. But none of this can stop patients’ desire for access to information regarding their care—laboratories, x-rays, medications, the results of their recent visit—or their desire to communicate directly with their providers, the speakers maintained.

“We have to find ways of improving outcomes and reducing overhead costs,” said Dr Presant, “but there is definitely improved patient satisfaction. Portals are here to stay. They are part of the future of healthcare.” l

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Disaster Planning

Disaster Planning for the Medical Office, Part 2

By Mariana S-B Lamb, MS, with contributions from Richard Levine, MD

E

very medical practice is at risk for a natural or man-made disaster. Those who have worked through a disaster will share their relief at having had a plan in place to get through it, or they may share, unfortunately, how much they wish they had developed a plan ahead of time. Crises such as a fire or weather event have the potential to be a major disruption to your business, and, should disaster strike, many will turn to the practice manager for a plan.

Since you never know when a crisis may strike, the best time to prepare is now. We hope this series of articles will guide you in your ongoing preparations, or perhaps will inspire you to start developing a plan. The first article in this series (“Bringing the Future into the Present: Disaster Planning for the Oncology Office,” Urology Practice Management, Volume 3, Number 5) addressed how to get started with your disaster planning as well as steps to take before a disaster strikes. This second article provides insights on how to involve patients in emergency planning, and what to do when a disaster is imminent, as well as before and after it strikes.

Staff members update the patient’s card after each treatment. If there is ever a need, the patient will then be able to access continuity of care with alternate health providers. Even in an emergency, most people will grab their wallet or purse as they run out the door, and their OPEN card is in their wallet. Further, as a backup, patients are encouraged to mail a copy of their card to a friend or family member who lives in a different area. Then, even if patients do not have their card, they will be able to retrieve their record of treatment from their backup contact person.

Aside from emergency planning, the OPEN card has helped patients even in day-to-day settings. One doctor shared that recently one of his oncology patients received treatment one morning, then found himself in the emergency department that very afternoon. He was unable to communicate the names of the drugs he had been given that day.

Fortunately, he was able to provide the OPEN card that had been updated by staff at his oncology visit.

When a Disaster Is Imminent If you are fortunate enough to Involving Patients in receive 24 hours or more advanced Emergency Planning warning of a pending disaster, you Recognizing that disasters are­ will have a chance to attend to some prone to occur—earthquakes in­ specific tasks to protect your pracCalifornia, hurricanes along the tice. It is important, however, to be East Coast, and floods in the practical. Do what you can without ­ Midwest—the Medical Oncology jeopardizing your life or the lives of Association of Southern California others. Stay in touch with authori(MOASC) launched the Oncolo­ ties to know when to evacuate. gy Patient Emergency Network Here are some tips to secure the (OPEN) in 2007. Key to that plan building and equipment when a disasis the creation of wallet-sized cards ter is on its way: (1) close window that patients carry with them; these blinds and coverings, and remove cards contain critical and updated flammable candles and lamps from information such as their diagnosis, the building; (2) move all furniture treatment, medications, and insur- and medical equipment (if feasible) ance carrier’s contact information. away from windows, and place them

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on counters or cabinets (off of the floor), covered in plastic sheeting tied or taped in place, if possible; (3) unplug all electrical equipment; (4) close and secure all doors and windows, evaluate the risk of vandalism, and barricade windows and doors with sandbags if possible or required; (5) clean out the breakroom refrigerator, remove all personal items, and remove all trash from premises.

To protect the business, you should secure business documents, equipment, and inventory. This includes securing both perishable and nonperishable inventory and removing and storing medication inventory offsite at a generator-serviced site or a site with secure power.

Inventory should be reported to the office manager. Finally, to coordinate patient continuity of care, contact patients and alternative physicians or hospitals to arrange referrals for potential future care of patients if needed, print out 2 weeks of patient schedules, maintain compliance with the Health Insurance Portability and Accountability Act, and provide patients with a copy of salient medical records. These should also be forwarded to previously identified alternative providers. Include treatment plans, a treatment summary, and follow-up plan documents, as well as a current medication list.

It is also important to get up-todate information and maintain contact with local and county medical societies, your state medical society, and state professional societies during an emergency. Keep a list of these in your disaster plan. Table 1 features some important contacts to get your list started.

When a Disaster Strikes When a disaster does hit, stay calm. Now is when you will appreci-

Disaster Planning

ate the time you put into advanced planning. In addition to the items addressed in our first article, be ready to perform the following steps: • Contact media on closing and opening of office • Evaluate the disaster site for any personnel injuries or deaths; confirm evacuation of the office by all individuals • Evaluate the need for containment and disposal of biohazard waste, as well as decontamination and radioactive fallout potential • Determine mobility (car, bus, train, airplane, fuel availability), and determine availability of water, food, electricity, communication, and shelters • Maintain contact with public service communication sources (weather stations, news stations, and security such as the police department, fire department, or highway patrol), as well as the American Cancer Society and the American Red Cross.

Conducting Research If you are involved in ongoing research, you will want to ensure that you are also prepared to maintain the integrity of that research in the event of a disaster. Refer to the Belmont Report1 for guidance on implications related to basic ethical principles of respect for persons (individual auto­ nomy, protection of individuals with reduced autonomy), beneficence (maximize benefits and minimize harms), and justice (equitable distribution of research risks and benefits).

In the midst of emergency situations, your goals remain the same, and are perhaps even more intensely highlighted: (1) to protect continuity in FDA-regulated studies; (2) to protect communication with regulatory authorities; (3) to keep patients informed about what to do; and (4) to ensure that the principal investigator maintains compliant with 45 CFR 46, the Department of Health & Human

Table 1 Contact Information for Government Agencies Centers for Medicare & Medicaid Services: www.cms.gov Federal Emergency Management Agency: www.fema.gov Department of Health & Human Services: www.dhhs.gov/emergency/index.shtml Centers for Disease Control and Prevention: www.bt.cdc.gov Pandemic flu: www.pandemic.flu.gov Agency for Healthcare Research and Quality: www.ahrq.gov/plep Food and Drug Administration: www.fda.gov IRB (if patients are in clinical trials): www.hhs.gov/ohrp/assurances/irb/ IRB indicates Institutional Review Board.

Table 2 Reopening the Practice After Disaster Strikes Determine status of security and of power supply Contact all vendors, banks, insurance companies, construction contractors, and cleaning companies to inform them to resume supply deliveries and services Assess and document any damage with photographs and videotape; make a list of lost and damaged items and their replacement or repair costs Contact insurance company representatives for appraisals, as needed Restock inventory of medical supplies, office supplies, and equipment; prioritize retrievals from offsite locations Contact patients to reschedule appointments onsite, offsite, or with alternative providers Reorder and restock chemotherapy and medication supplies Evaluate and reestablish computer network, telephone, and security systems Evaluate functionality of equipment, recalibrate, and perform quality-control test

Services regulatory code regarding the protection of human subjects in research, specifically relating to unanticipated problems involving risk to patients or others, suspension of trials, and termination of trials.

helped you consider preparations to make for a potential disaster. While we cannot predict when or if a dis­ aster will strike, we can put steps and processes in place now to help plan for one and ensure continuity of care.

As practice managers, our staff members and the patients we serve will turn to us for answers in the event of a dis­aster. With proper planning, we can offer our team members and patients the answers, guidance, and reassurance they need in a time of turmoil. l

After a Disaster The Disaster Plan Coordinator will maintain communication with area emergency teams and notify staff when it is safe to reopen the office. Staff will initiate responsibilities to reestablish the practice.

The list in Table 2 should serve as a guide to facilitate an organized, wellplanned reopening of the practice.

Reference

1. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.

Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. www. hhs.gov/ohrp/humansubjects/guidance/belmont.html.

Published April 18, 1979. Accessed October 10, 2014.

Conclusion We hope this 2-part series has

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Wealth Management

Ten Tips to Cut Your 2014 Taxes

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

er to withhold additional taxes if you have not had enough taxes withheld during the year. The IRS Withholding Calculator for 2015 is available at www.irs.gov/Individuals/ IRS-Withholding-Calculator.

Andrew D. Schwartz

4

Consider selling your investments held in nonretirement accounts that have depreciated.

Since 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, wait at least 31 days before buying back security sold at a loss, or the IRS will not allow the loss under “wash sale” rules.

Lawrence B. Keller

M

ost people are 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? This article provides 10 potential tax-saving opportunities for 2014. The key is to take the time to evaluate which of these concepts, if any, may work in your situation. There is still time to take advantage of these 10 tax-saving opportunities before December 31, 2014.

5

If you are in the lowest tax bracket, consider selling your investments that have increased in value.

Since the capital gains rate will be 0%, those securities can be bought back, and the “cost-basis” will be the higher amount. This strategy will save you taxes when you sell these securities in the future. Ensure that the capital gains realized don’t push you out of the 15% tax bracket, or you will be taxed on gains that fall outside that range.

1

If you have not been contributing to your 401(k) and 403(b) plans at the maximum rate all year, increase your contributions. This year, you can put up to $17,500 into your 401(k) or 403(b) plan. Anyone aged ≥50 years by December 31, 2014, 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.

6

Send in your January 2015 mortgage payment early enough for processing before December 31, 2014. You can deduct the interest portion of that payment a year earlier by sending in your payment a few weeks early.

2

If you are self-employed, consider setting up a Solo 401(k) by December 31, 2014. A Solo 401(k) plan allows a self-employed person to reach the $52,000 retirement plan maximum with less income than a SEP-IRA. It also allows people aged ≥50 years to put away an additional $5500 (for a total of $57,500) into a retirement plan for 2014.

7

3

To avoid an underpayment penalty, review your withholdings and instruct your employ-

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Clean out your closets; donate your clothing and household items to a charitable organization, since itemized “noncash” contributions are tax deductible.

Remember to get a receipt. Make an itemized list that includes condition of the donated items, and take

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December 2014

a few pictures of the items as well.

Only donations of clothing and household items in “good condition or better” qualify for a deduction.

8

Making monetary donations by credit card before December 31, 2014, allows you to deduct the donation on this year’s return, even if you don’t pay your credit card bill until 2015. You always have the option of donating to charities any investments that have appreciated. You can claim your donation based on the value of the donated assets without paying capital gains taxes on the appreciation.

9

Prepay your projected state tax shortfall if you will be itemizing your deductions and you will not be subject to the alternative minimum tax.

10

Prepay and pay off your medical bills if your total medical expenses exceed 10% of your income and you itemize. The threshold increased from 7.5% to 10% in 2013, except for people aged >65 years, for whom the threshold remains at 7.5%.

This month, evaluate whether you will save taxes by postponing 2014 income or deductions into 2015 or by accelerating 2015 income or deductions into 2014. l Andrew D. Schwartz, CPA, is a partner in the Boston CPA firm Schwartz & Schwartz, PC, and is also the founder of the MDTAXES Network (www. mdtaxes.com). He can be reached at 800-471-0045 or by e-mail to Andrew@ mdtaxes.com.

Lawrence B. Keller, CFP®, CLU®, ChFC®, RHU®, LUTCF, is the founder of Physician Financial Services. He can be reached at 800-481-6447 or by e-mail to Lkeller@physicianfinancial services.com.

Invitation to Join the UPM Editorial Board The publishers of Urology Practice Management™ (UPM) are inviting qualified urology practice owners and administrators to participate as members of the UPM Editorial Board. As an Editorial Board member, you will play an active role in helping to shape the content of this exciting new publication.

Urology Practice Management is a niche publication focused on process solutions for urology practices. UPM is designed to provide the urology care team—medical, practice administrators, coders, and billers—with the knowledge and skills required to keep abreast of today’s fast-changing business environment, allowing practice professionals more time to concentrate on high-quality patient care. Each issue of UPM will focus on various areas of urology practice, featuring current topics such as:

Urology P ractice Managem ent

• Healthcare technology • Models of care • Staffing • Reimbursement and coding

PROCES

MAY 201 3

Take advantage of this unique opportunity to help your peers and enhance your professional reputation by becoming the newest member of the UPM Editorial Board. an affiliate of

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Human Resources

Tattletale or Whistleblower: What’s an Employer to Do?

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

A

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quick review of the evening news will often reveal stories of someone in an organization either doing wrong or blowing the whistle on someone else who did wrong. No organization is immune from having its reputation questioned when an employee or manager is caught violating ethical or legal standards, and the fallout can be damaging in many ways.

We read almost daily about deliberate misdeeds, illegal behaviors, or unethical acts. Many of these behaviors have come to light because a current or former employee felt that pursuing corrective actions via internal avenues would be ineffective. Yet many people also remain silent out of fear of retaliation. When the wrongdoing is ultimately revealed, this act is referred to as “whistleblowing.”

In certain cases, whistleblowing can be profitable. In a recent medical billing case in Kentucky, a physician was awarded $283,412.90 as part of a settlement.1 Some elements of this case and its settlement fell under the whistleblower provisions of the federal False Claims Act, which allows private citizens with knowledge of fraud to bring civil actions on behalf of the United States, and to share in any recovery.1 In other organizations (businesses, nonprofits, and government, small or large) opportunities exist daily for people to choose whether to behave in a legal and ethical manner. Those who choose not to usually have a financial need, an opportunity (access to cash, data, or other company assets), and a rationalization for their behavior.

It is common to wonder why people make unethical or illegal

choices, rather than adhere to the laws, regulations, and rules of common decency in their working lives.

Another question, however, may be equally as relevant: Why do those who have knowledge of such acts remain silent? A recent National Business Ethics Survey found that about one third of workers who witness misconduct do not report it.2 So, what is an employer to do?

High retaliation rates will dampen reporting and increase the likelihood that wrong behavior remains undiscovered. As such, there are tactical responses to the abovementioned question, keeping in mind that good tactics can never compensate for a bad strategy. The real challenge is to create a culture of ethical decision-making and behavior. Some suggestions to achieve this are presented below, and should only be implemented with the support of your upper management team. They include the following: • Manifest the organization’s position on ethical behavior through all available forms of communication; written standards are imperative. Meetings at all levels serve to maintain an aura of transparency, and can set an example for ethical expectations.

• Train everyone on standards and

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December 2014

relevant topics for the organization’s sphere of operations, and provide a resource for employees to turn to, such as a specific executive or human resources leader.

• Promulgate a policy and position for everyone to sign. Include a process for internally expressing concerns about suspected or witnessed questionable behavior. An ethics or “whistleblower” hotline can be especially valuable. All policies should receive legal review, address the company’s position and standards clearly, provide examples of prohibited behavior and for reporting possible violations, and clearly prohibit retaliation against anyone who reports possible violations.

• Include in staff performance appraisals and job descriptions a section on level of compliance with company policies. Employee surveys can also support a compliance effort.

• Clarify sanctions for all violators.

Ethical behavior necessarily deals with the vagaries of human life, and it is important to remain flexible enough to account for variety and unexpected possibilities in the working world. Providing clear expectations, support, and processes to achieve an ethical culture is the real challenge for any organization seeking to create and sustain an engaged workforce. Executives, owners, and human resources professionals are especially suited to lead such efforts. l

References

1. The United States Attorney’s Office, Western District of Kentucky. Owners of Elizabethtown ­ Hematology Oncology, PLC agree to pay over $3.7 ­ ­ million to settle false billings to government health c­are programs. www.justice.gov/usao/kyw/news/­ ­ 2014/20140603-03.html. Accessed November 10, 2014.

2. Ethics Resource Center. National business ethics survey of the US workforce. www.ethics.org/downloads/2013 NBESFinalWeb.pdf. Accessed November 6, 2014.

Patient and Provider Access

2014 Election Is in the Books: What Will It Mean for Healthcare in 2015?

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

T

he 2014 elections are complete, and we now know the makeup of the next US Congress. Even though Republicans picked up more than the 6 seats needed to take control of the Senate, it may not mean that significant healthcare changes are imminent. As the congressional landscape transforms, legislators will have to address the following issues.

The Affordable Care Act (ACA): There is little chance of seeing this act repealed or replaced with President Barack Obama still in office, as it is one of his most significant legislative achievements. He will not have an interest in repealing it, and the Senate does not have the two-thirds majority to overcome a presidential veto. We do know, however, that aspects of the law will be up for repeal or tweaking, including the medical device excise tax (2.3% of the sales price on certain medical devices); the employer mandate to offer qualified, affordable health coverage; and the 30-hours-per-week definition for a full-time employee. The bottom line is that even if Republicans control Congress, it is expected the ACA will remain largely intact.

The real future of the ACA likely lies with the US Supreme Court.

Earlier this year, conflicting rulings came from the Appeals Courts on the legality of the ability of federally run exchanges to offer premium assistance, as the law only allows subsidies for citizens signing up for insurance through state-based exchanges. The Supreme Court’s ruling that is expected in June 2015 could have enormous implications for the success of the law with the

federal marketplace in 36 states.

Another area that may see movement is the 21st Century Cures initiative: In 2014 the US House of Representatives Energy & Commerce Committee hosted hearings and roundtables to study issues that affect healthcare and innovation. In early 2015, the committee plans to introduce a bill that will address numerous issues, including one that touches on clinical trials.

pass another long-term SGR fix in 2015, they will still run into issues with cost. Although it is likely the new Congress will bring up a long-term fix, do not be surprised if another short-term fix is the solution.

• Sequestration: For more than 18 months providers have faced sequester-mandated cuts to Medicare payments, and more than 10 years remain of the 2% Medicare claims reduction.

This year, H.R. 1416, a bill that halts the cuts on reimbursement for cancer drugs, garnered some support, but not enough to pass in either chamber of Congress.

Many advocacy organizations will push to have the bill reintroduced, but H.R. 1416 will be difficult to pass as part of any stand-alone healthcare bill.

The best chance for a solution will be to attach some kind of fix to a larger bill, such as SGR reform.

A number of other issues may come up during the year, including oral parity and prompt pay discounts. These issues may be included in larger healthcarerelated vehicles. The Association of Community Cancer Centers will host a Capitol Hill Day for its members on March 16, 2015.

We encourage all of our members to attend this annual event and educate elected officials on these important issues. l

Bipartisan-Supported Legislation The following issues largely have bipartisan support, so the makeup of Congress is not as important for these issues as are the methods decided upon to pay for them. Both houses of Congress have indicated they will prioritize legislation that has bipartisan support; the challenge will be finding ways to offset the cost.

• The Sustainable Growth Rate (SGR): The best opportunity to permanently repeal SGR occurred this year. A bipartisan bill on this matter had broad support, but Congress could not come together to determine how to pay for the cost of a fix ($130 billion). Instead, Congress passed another short-term patch that will expire in March 2015, which prevented roughly a 24% cut in Medicare physician reimbursement rates for 12 months.

In keeping with previous fixes, Congress cut healthcare expenditures to pay for the extension. It also extended Medicare sequestration-mandated cuts by 2 more years. If Congress is to try to

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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 Edema4 26.7 1.9 18.3 0.8 Vascular disorders Hot flush 19.0 0.3 16.8 0.3 Hypertension 8.5 1.3 6.9 0.3 Gastrointestinal disorders Diarrhea 17.6 0.6 13.5 1.3 Dyspepsia 6.1 0 3.3 0 Infections and infestations Urinary tract infection 11.5 2.1 7.1 0.5 Upper respiratory tract infection 5.4 0 2.5 0 Respiratory, thoracic and mediastinal disorders Cough 10.6 0 7.6 0 Renal and urinary disorders Urinary frequency 7.2 0.3 5.1 0.3 Nocturia 6.2 0 4.1 0 Injury, poisoning and procedural complications Fractures5 5.9 1.4 2.3 0 Cardiac disorders Arrhythmia6 7.2 1.1 4.6 1.0 Chest pain or chest discomfort7 3.8 0.5 2.8 0 Cardiac failure8 2.3 1.9 1.0 0.3

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

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

Table 3: Adverse Reactions in ≥5% of Patients on the ZYTIGA Arm in Study 2 (continued) ZYTIGA with Placebo with Prednisone (N=542) Prednisone (N=540) 1 System/Organ Class All Grades Grade 3-4 All Grades Grade 3-4 Adverse reaction % % % % Renal and urinary disorders Hematuria 10.3 1.3 5.6 0.6 Skin and subcutaneous tissue disorders Rash 8.1 0.0 3.7 0.0 1 Adverse events graded according to CTCAE version 3.0 2 Includes terms Edema peripheral, Pitting edema, and Generalized edema 3 Includes terms Arthritis, Arthralgia, Joint swelling, and Joint stiffness

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

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

8 Includes terms Cardiac failure, Cardiac failure congestive, Left ventricular dysfunction, Cardiogenic shock, Cardiomegaly, Cardiomyopathy, and Ejection fraction decreased 4 Includes

Table 2 shows laboratory abnormalities of interest from Study 1. Grade 3-4 low serum phosphorus (7%) and low potassium (5%) occurred at a greater than or equal to 5% rate in the ZYTIGA arm.

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

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

The median duration of treatment with ZYTIGA was 13.8 months.

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

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

Table 4: Laboratory Abnormalities in >15% of Patients in the ZYTIGA Arm of Study 2 Abiraterone (N=542) Placebo (N=540) Laboratory Grade 1-4 Grade 3-4 Grade 1-4 Grade 3-4 Abnormality % % % % Hematology Lymphopenia 38.2 8.7 31.7 7.4 Chemistry Hyperglycemia1 56.6 6.5 50.9 5.2 High ALT 41.9 6.1 29.1 0.7 High AST 37.3 3.1 28.7 1.1 Hypernatremia 32.8 0.4 25.0 0.2 Hypokalemia 17.2 2.8 10.2 1.7 1Based on non-fasting blood draws Cardiovascular Adverse Reactions: In the combined data for studies 1 and 2, cardiac failure occurred more commonly in patients treated with ZYTIGA compared to patients on the placebo arm (2.1% versus 0.7%).

Grade 3-4 cardiac failure occurred in 1.6% of patients taking ZYTIGA and led to 5 treatment discontinuations and 2 deaths. Grade 3-4 cardiac failure occurred in 0.2% of patients taking placebo. There were no treatment discontinuations and one death due to cardiac failure in the placebo group.

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

Post Marketing Experience The following additional adverse reactions have been identified during post approval use of ZYTIGA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Respiratory, Thoracic and Mediastinal Disorders: non-infectious pneumonitis.

DRUG INTERACTIONS Drugs that Inhibit or Induce CYP3A4 Enzymes: Based on in vitro data, ZYTIGA is a substrate of CYP3A4.

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

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

Effects of Abiraterone on Drug Metabolizing Enzymes: ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when

ZYTIGA® (abiraterone acetate) Tablets

ZYTIGA® (abiraterone acetate) Tablets

dextromethorphan was given with abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. Avoid co-administration of abiraterone acetate with substrates of CYP2D6 with a narrow therapeutic index (e.g., thioridazine).

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

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

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

OVERDOSAGE Human experience of overdose with ZYTIGA is limited.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 Based on in vitro data, ZYTIGA® is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA® treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA® dosing frequency only during the co-administration period [see Dosage and Administration (2.3)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

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

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

Please see Brief Summary of Prescribing Information on adjacent pages. © Janssen Biotech, Inc. 2014

11/14

006076-141015

Our goal is to help make access to ZYTIGA®(abiraterone acetate) easy.

Support for you: 4-6

Support for your patients:

Rapid investigation and assessment of patient eligibility and coverage • Prior authorization support • Information on cost support options, including updates on independent foundation funding status • Electronic enrollment through an online portal • Identification of a Specialty Pharmacy Provider (SPP) • Access to medication order information • A personally-assigned Site Coordinator Business Hours

• Explanation of benefits from a personally-assigned Care Coordinator • Referral to cost support options, including the ZytigaOne® Instant Savings Program for eligible patients • Upon request, follow-up status calls to those referred for cost support • Coordination with SPP for processing and delivery of medication • Educational materials and personalized prescription reminders, if requested

Take advantage of ZytigaOne® Support today.

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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 The Lash Group, Inc., under contract for Janssen Biotech, Inc. In this regard, The Lash Group, lnc., assists 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. This reimbursement support service has no independent value to providers apart from the product and is included within the cost of the product.

Importantly, insurance verification is the ultimate responsibility of the provider. Third-party reimbursement is affected by many factors. This document is presented for informational purposes only and is not intended to provide reimbursement or legal advice and does not promise or guarantee coverage, levels of reimbursement, payment or charge. Similarly, all CPT and HCPCS codes are supplied for informational purposes only and represent no promise or guarantee that these codes will be appropriate or that reimbursement will be made. It is not intended to increase or maximize reimbursement by any payer. Laws, regulations and policies concerning reimbursement are complex and are updated frequently. While we have made an effort to be current as of the issue date of this document the information may not be as current or comprehensive when you view it. We strongly recommend you consult with your counsel, payer organization, or reimbursement specialist for any reimbursement or billing questions. While The Lash Group, Inc., attempts to provide correct information, they and Janssen Biotech, Inc., make no representations or warranties, expressed or implied, as to the accuracy of the information. In no event shall The Lash Group, Inc., Janssen Biotech, Inc., 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, Inc. 2014 11/14 006076-141015