Abiraterone in metastatic prostate cancer without previous chemotherapy.
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 progression-free 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. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.).
Ryan, CJ; Smith, MR; de Bono, JS; Molina, A; Logothetis, CJ; de Souza, P; Fizazi, K; Mainwaring, P; Piulats, JM; Ng, S; Carles, J; Mulders, PFA; Basch, E; Small, EJ; Saad, F; Schrijvers, D; Van Poppel, H; Mukherjee, SD; Suttmann, H; Gerritsen, WR; Flaig, TW; George, DJ; Yu, EY; Efstathiou, E; Pantuck, A; Winquist, E; Higano, CS; Taplin, M-E; Park, Y; Kheoh, T; Griffin, T; Scher, HI; Rathkopf, DE; COU-AA-302 Investigators,
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