FDA Approves Enzalutamide for Castration-Resistant Prostate Cancer

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ON JULY 13, 2018, the U.S. Food and Drug Administration (FDA) approved enzalutamide (Xtandi) for patients with castration-resistant prostate cancer (CRPC). This approval broadens the indicated patient population to include patients with either nonmetastatic CRPC or metastatic CRPC. Enzalutamide was previously approved for the treatment of patients with metastatic CRPC. 

Approval in patients with nonmetastatic CRPC was based on the randomized, multicenter PROSPER clinical trial, which randomized 1,401 patients 2:1 to either enzalutamide at 160 mg orally once daily or placebo orally once daily. Patients continued on gonadotropin-releasing hormone (GnRH) therapy or had prior bilateral orchiectomy. 

Efficacy and Toxicity 

THE MAJOR EFFICACY outcome was metastasis-free survival, defined as the time from randomization to locoregional and/or distant radiographic progression (blinded independent central review) or death up to 112 days after treatment discontinuation without radiographic progression. The trial demonstrated a statistically significant improvement in metastasis-free survival for patients receiving enzalutamide compared to those receiving placebo, with median metastasis-free survival of 36.6 and 14.7 months, respectively (hazard ratio = 0.29, 95% confidence interval = 0.24–0.35; P < .0001). 

The most common adverse reactions (≥ 10%) that occurred more frequently (≥ 2% over placebo) in the enzalutamide-treated patients in PROSPER were asthenia/fatigue, hot flush, hypertension, dizziness, nausea, and falls. Grade 3 or higher adverse reactions were reported in 31% of men treated with enzalutamide plus androgen-deprivation therapy and in 23% of men treated with androgen-deprivation therapy alone. 

The recommended dose of enzalutamide is 160 mg (four 40-mg capsules) administered orally once daily. 

Data from the PROSPER study were presented at the 2018 Genitourinary Cancers Symposium1 in February 2018 and published by Hussain et al in The New England Journal of Medicine.2 ■


1. Hussain M, et al: PROSPER: A phase 3, randomized, double-blind, placebo-controlled study of enzalutamide in men with nonmetastatic castration-resistant prostate cancer. 2018 Genitourinary Cancers Symposium. Abstract 3. Presented February 8, 2018

2. Hussain M, et al: Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Eng J Med 378: 2465–2474, 2018.