Enzalutamide in Metastatic Prostate Cancer before Chemotherapy

作者：Tomasz M. Beer, Andrew J. Armstrong, Dana E. Rathkopf, Yohann Loriot, Cora N. Sternberg, Celestia S. Higano, Peter Iversen, Suman Bhattacharya, Joan Carles, Simon Chowdhury, Ian D. Davis, Johann S. de Bono, Christopher P. Evans, Karim Fizazi, Anthony M. Joshua, Choung‐Soo Kim, Go Kimura, Paul N. Mainwaring, Harry H. Mansbach, Kurt Miller, Sarah B. Noonberg, Frank Perabo, De Phung, Fred Saad, Howard I. Scher, Mary‐Ellen Taplin, Peter Venner, Bertrand Tombal · 发表于：New England Journal of Medicine · 年份：2014 · DOI：10.1056/nejmoa1405095 · 被引用次数：3072 · 研究领域：Prostate Cancer Treatment and Research、Prostate Cancer Diagnosis and Treatment、Bone health and treatments

BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival. RESULTS: The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until ...