Enzalutamide for Castration-Resistant PSA-Only Prostate Cancer

Earlier this year, the nonsteroidal antiandrogen agent apalutamide was shown to be effective, and was FDA approved, for patients with castration-resistant PSA-only prostate cancer (NEJM JW Oncol Hematol Apr 2018 and N Engl J Med 2018; 378:1408).

Now, international investigators have conducted an industry-sponsored, double-blind, randomized, phase III trial of a similar nonsteroidal antiandrogen agent, enzalutamide, versus placebo in 1401 patients (median age, 73–74 years) with nonmetastatic, castration-resistant prostate cancer, a rapidly rising prostate-specific antigen (PSA) level (median PSA doubling time, 3.7 months), and evidence of castrate levels of testosterone (<50 ng/dL).

With a median follow-up of 18.5 months in the enzalutamide group and 15.1 months in the placebo group, the median metastasis-free survival (the primary endpoint) was prolonged with enzalutamide versus placebo (36.6 vs. 14.7 months; hazard ratio, 0.29; P=0.001). Grade 3 or higher adverse events were more likely with enzalutamide (31% vs. 23%). Of note, the most common adverse events leading to death were cardiac events, which occurred with higher frequency in the enzalutamide arm. The main reason for drug discontinuation was disease progression, which was less likely with enzalutamide than with placebo (15% vs. 44%).