Abiraterone and Increased Survival in Metastatic Prostate Cancer

作者：De Bono Johann S^*; Logothetis Christopher J; Molina Arturo; Fizazi Karim; North Scott; Chu Luis; Chi Kim N; Jones Robert J; Goodman Oscar B Jr; Saad Fred; Staffurth John N; Mainwaring Paul; Harland Stephen; Flaig Thomas W; Hutson Thomas E; Cheng Tina; Patterson Helen; Hainsworth John D; Ryan Charles J; Sternberg Cora N; Ellard Susan L; Flechon Aude; Saleh Mansoor; Scholz Mark; Efstathiou Eleni; Zivi Andrea; Bianchini Diletta; Loriot Yohann

来源：New England Journal of Medicine, 2011, 364(21): 1995-2005.

DOI：10.1056/NEJMoa1014618

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 pre-planned 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 ClinicalTrials.gov number, NCT00638690.)

• 出版日期2011-5-26