Background: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. Methods: In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. Results: The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progressionfree survival was 16.5 months with abiraterone - prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone - prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone - prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P = 0.01) but did not cross the efficacy boundary. Abiraterone - prednisone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone. Conclusions: Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer.
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