- Ryan, Charles J;
- Smith, Matthew R;
- de Bono, Johann S;
- Molina, Arturo;
- Logothetis, Christopher J;
- de Souza, Paul;
- Fizazi, Karim;
- Mainwaring, Paul;
- Piulats, Josep M;
- Ng, Siobhan;
- Carles, Joan;
- Mulders, Peter FA;
- Basch, Ethan;
- Small, Eric J;
- Saad, Fred;
- Schrijvers, Dirk;
- Van Poppel, Hendrik;
- Mukherjee, Som D;
- Suttmann, Henrik;
- Gerritsen, Winald R;
- Flaig, Thomas W;
- George, Daniel J;
- Yu, Evan Y;
- Efstathiou, Eleni;
- Pantuck, Allan;
- Winquist, Eric;
- Higano, Celestia S;
- Taplin, Mary-Ellen;
- Park, Youn;
- Kheoh, Thian;
- Griffin, Thomas;
- Scher, Howard I;
- Rathkopf, Dana E
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.).