• Charles J Ryan, Matthew R Smith, Johann S de Bono, Arturo Molina, Christopher J Logothetis, Paul de Souza, Karim Fizazi, Paul Mainwaring, Josep M Piulats, Siobhan Ng, Joan Carles, Peter F A Mulders, Ethan Basch, Eric J Small, Fred Saad, Dirk Schrijvers, Hendrik Van Poppel, Som D Mukherjee, Henrik Suttmann, Winald R Gerritsen, Thomas W Flaig, Daniel J George, Evan Y Yu, Eleni Efstathiou, Allan Pantuck, Eric Winquist, Celestia S Higano, Mary-Ellen Taplin, Youn Park, Thian Kheoh, Thomas Griffin, Howard I Scher, Dana E Rathkopf, and COU-AA-302 Investigators.
• Genitourinary Medical Oncology Program, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA. ryanc@medicine.ucsf.edu
• N. Engl. J. Med.. 2013 Jan 10;368(2):138-48.

BackgroundAbiraterone 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.MethodsIn 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.ResultsThe 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.ConclusionsAbiraterone 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.).

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