Abiraterone and increased survival in metastatic prostate cancer

Johann S. De Bono, Christopher J. Logothetis, Arturo Molina, Karim Fizazi, Scott North, Luis Chu, Kim N. Chi, Robert J. Jones, Oscar B. Goodman, Fred Saad, John N. Staffurth, Paul Mainwaring, Stephen Harland, Thomas W. Flaig, Thomas E. Hutson, Tina Cheng, Helen Patterson, John D. Hainsworth, Charles J. Ryan, Cora N. SternbergSusan L. Ellard, Aude Fléchon, Mansoor Saleh, Mark Scholz, Eleni Efstathiou, Andrea Zivi, Diletta Bianchini, Yohann Loriot, Nicole Chieffo, Thian Kheoh, Christopher M. Haqq, Howard I. Scher

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    Abstract

    BACKGROUND: Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy. METHODS: We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate. RESULTS: After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate-prednisone group than in the placebo - prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate-prednisone group than in the placebo - prednisone group. CONCLUSIONS: The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 Clinical Trials. gov number, NCT00638690.)

    Original languageEnglish
    Pages (from-to)1995-2005
    Number of pages11
    JournalNew England Journal of Medicine
    Volume364
    Issue number21
    DOIs
    Publication statusPublished - 26 May 2011

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