[HTML][HTML] Abiraterone in metastatic prostate cancer without previous chemotherapy

CJ Ryan, MR Smith, JS De Bono… - … England Journal of …, 2013 - Mass Medical Soc
CJ Ryan, MR Smith, JS De Bono, A Molina, CJ Logothetis, P De Souza, K Fizazi…
New England Journal of Medicine, 2013Mass Medical Soc
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 …
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.)
The New England Journal Of Medicine