TY - JOUR
T1 - Abiraterone in metastatic prostate cancer without previous chemotherapy
AU - Ryan, Charles J.
AU - Smith, Matthew R.
AU - De Bono, Johann S.
AU - Molina, Arturo
AU - Logothetis, Christopher J.
AU - De Souza, Paul
AU - Fizazi, Karim
AU - Mainwaring, Paul
AU - Piulats, Josep M.
AU - Ng, Siobhan
AU - Carles, Joan
AU - Mulders, Peter F.A.
AU - Basch, Ethan
AU - Small, Eric J.
AU - Saad, Fred
AU - Schrijvers, Dirk
AU - Van Poppel, Hendrik
AU - Mukherjee, Som D.
AU - Suttmann, Henrik
AU - Gerritsen, Winald R.
AU - Flaig, Thomas W.
AU - George, Daniel J.
AU - Yu, Evan Y.
AU - Efstathiou, Eleni
AU - Pantuck, Allan
AU - Winquist, Eric
AU - Higano, Celestia S.
AU - Taplin, Mary Ellen
AU - Park, Youn
AU - Kheoh, Thian
AU - Griffin, Thomas
AU - Scher, Howard I.
AU - Rathkopf, Dana E.
PY - 2013/1/10
Y1 - 2013/1/10
N2 - 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 progressionfree 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.
AB - 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 progressionfree 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.
UR - http://www.scopus.com/inward/record.url?scp=84872078210&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1209096
DO - 10.1056/NEJMoa1209096
M3 - Article
AN - SCOPUS:84872078210
SN - 0028-4793
VL - 368
SP - 138
EP - 148
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 2
ER -