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AUANEWS December 2014 23

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 fl ush, 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 Insuffi ciency (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 Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress.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 confi rm 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 fl uid retention. ZYTIGA® may cause hypertension, hypokalemia, and fl uid 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 fl uid 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.

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James E. Montie, MD Ann Arbor, Michigan

Djulbegovic B and Guyatt GH: Evidence-based practice is not

synonymous with delivery of uniform health care. JAMA 2014; 312: 1293-1294.

Hoffman TC, Montori VM and Del Mar C: The connection be- tween evidence-based medicine and shared decision making. JAMA 2014; 312: 1295-1296.

Kane HL, Halpern MT, Squiers LB et al: Implementing and evaluating shared decision making in oncolo- gy practice. Ca Cancer J Clin 2014; 64: 377–388.

Thompson IM Jr, Leach RJ and Ankerst DP: Focusing PSA testing on detection of high-risk prostate cancers by incorporating patient preferences into decision making. JAMA 2014; 312: 995-996.

Vickers AJ, Edwards K, Cooperberg MR et al: A simple schema for informed decision making about prostate cancer screening. Ann Intern Med 2014; 161: 441-442.

The fi rst 3 articles deal with general aspects of evidence-based medicine (EBM). Djulbegovic and Guyatt stress that attempts to achieve uniformity of practice as an end are misguided. “…If values and prefer- ences differ widely across patients (which is often if not uniformly the case), the right decision for one pa- tient may be the wrong decision for another.” This is particularly true in many urological conditions in which the guideline recommendations are unavoidably weak.

Hoffman et al add that practition- ers need to recognize that EBM and shared decision making (SDM) are essential to quality health care. One cannot achieve its aims without the other. “Without SDM, EBM can turn into evidence tyranny….Likewise, without attention to the principles of EBM, SDM becomes limited be- cause a number of its steps are inextri- cably linked to the evidence.”

Kane et al emphasize the patient and physician factors that can make

HAVE YOU Read? SDM successful. Decision aids are tools to help patients make well-in- formed and preference sensitive deci- sions. It should be noted that decision aids are “…designed to support—not replace—provider counseling.”

The next articles focus specifi cally on prostate specifi c antigen (PSA) testing and SDM. There is no dis- agreement that innovation is needed to ensure that PSA testing does more good than harm. Thompson et al posit that a PSA result should not be listed as normal or elevated, but instead should be personalized, and

linked to the likelihood of no can- cer, low grade cancer or high grade cancer using the Prostate Cancer Prevention Trial risk calculator 2.0. Such information should assist the patient in the decision about whether to proceed with testing.

Vickers et al take a provocative step further and suggest that after the patient understands some basic facts about prostate cancer, if he is uncomfortable knowing that he has a cancer and not treating it, then

24 December 2014 AUANEWS

More than 1,000 days. And every day tells a story.

For men with mCRPC who progressed on ADT

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

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

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

5.2 35.3

Co-primary end point—overall survival: hazard ratio (HR)=0.792; 95% CI: 0.655, 0.956; P=0.0151; prespecifi ed value for statistical signifi cance 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.

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

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

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 fi rst 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 fi ve 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 effi cacy end points were overall survival (OS) and radiographic progression-free survival.

ADT=androgen-deprivation therapy.

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Have You Read? ▼ Continued from page 23

screening may not be for him. This is based on the greater likelihood of fi nding a cancer that does not need treatment than one that does. On the other hand, if the patient is confi dent that he would accept treatment for aggressive cancer and would not be unduly worried about living with a cancer that is low risk, then the pa- tient would be a good candidate for screening.

Smith-Bindman R, Aubin C, Bailitz J et al: Ultrasonography versus computed tomography for suspected nephrolithiasis. N Engl J Med 2014; 371: 1100-1110.

This article stimulated much debate in social media. In this pro- spective, randomized trial including 2,759 patients with suspected neph- rolithiasis assigned to point of care ultrasonography (US), radiology US or computerized tomography (CT), ultrasonography demonstrated “lower cumulative radiation exposure than

initial CT, without signifi cant dif- ferences in high-risk diagnoses with complications, serious adverse events, pain scores, return to emergency de- partment visits, or hospitalizations.”

Surprisingly, time spent in the emergency department was longer in the radiology US group (7.0 hours) than point of care US (6.3 hours) or CT (6.4 hours). This fi nding suggests that US should be the preferred ini- tial study. Followup CT was needed in 40.7% and 27% of the patients receiving point of care US and radiol- ogy US, respectively. In the initial CT

group only 5.1% of patients needed a later US.

A noteworthy point was that the sensitivity for the detection of neph- rolithiasis was signifi cantly higher in the CT group. Thus, for example, the provider may learn that the patient had hydronephrosis from US but CT may be able to show that it was due to a 3 mm calculus at the ureterovesical junction. In addition, new generation CT will deliver substantially less ra- diation. ◆

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