Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065, USA.
N Engl J Med. 2012 Sep 27;367(13):1187-97. doi: 10.1056/NEJMoa1207506. Epub 2012 Aug 15.
Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor-signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy.
In our phase 3, double-blind, placebo-controlled trial, we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity. We randomly assigned them, in a 2:1 ratio, to receive oral enzalutamide at a dose of 160 mg per day (800 patients) or placebo (399 patients). The primary end point was overall survival.
The study was stopped after a planned interim analysis at the time of 520 deaths. The median overall survival was 18.4 months (95% confidence interval [CI], 17.3 to not yet reached) in the enzalutamide group versus 13.6 months (95% CI, 11.3 to 15.8) in the placebo group (hazard ratio for death in the enzalutamide group, 0.63; 95% CI, 0.53 to 0.75; P<0.001). The superiority of enzalutamide over placebo was shown with respect to all secondary end points: the proportion of patients with a reduction in the prostate-specific antigen (PSA) level by 50% or more (54% vs. 2%, P<0.001), the soft-tissue response rate (29% vs. 4%, P<0.001), the quality-of-life response rate (43% vs. 18%, P<0.001), the time to PSA progression (8.3 vs. 3.0 months; hazard ratio, 0.25; P<0.001), radiographic progression-free survival (8.3 vs. 2.9 months; hazard ratio, 0.40; P<0.001), and the time to the first skeletal-related event (16.7 vs. 13.3 months; hazard ratio, 0.69; P<0.001). Rates of fatigue, diarrhea, and hot flashes were higher in the enzalutamide group. Seizures were reported in five patients (0.6%) receiving enzalutamide.
Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy. (Funded by Medivation and Astellas Pharma Global Development; AFFIRM ClinicalTrials.gov number, NCT00974311.).
恩杂鲁胺（以前称为 MDV3100）针对雄激素受体信号通路的多个步骤，这是前列腺癌生长的主要驱动因素。我们旨在评估恩杂鲁胺是否能延长化疗后去势抵抗性前列腺癌患者的生存时间。
在我们的 3 期、双盲、安慰剂对照试验中，我们根据东部合作肿瘤组表现状态评分和疼痛强度，对 1199 名化疗后去势抵抗性前列腺癌男性进行分层。我们以 2:1 的比例随机分配他们每天接受 160 毫克口服恩杂鲁胺（800 名患者）或安慰剂（399 名患者）。主要终点是总生存。
在计划的中期分析时，研究在 520 例死亡时停止。恩杂鲁胺组的中位总生存期为 18.4 个月（95%置信区间[CI]，17.3 至未达到），安慰剂组为 13.6 个月（95%CI，11.3 至 15.8）（恩杂鲁胺组死亡风险比为 0.63；95%CI，0.53 至 0.75；P<0.001）。与安慰剂相比，恩杂鲁胺在所有次要终点均显示出优越性：前列腺特异性抗原（PSA）水平降低 50%或更多的患者比例（54% vs. 2%，P<0.001），软组织反应率（29% vs. 4%，P<0.001），生活质量反应率（43% vs. 18%，P<0.001），PSA 进展时间（8.3 个月 vs. 3.0 个月；风险比，0.25；P<0.001），放射学无进展生存期（8.3 个月 vs. 2.9 个月；风险比，0.40；P<0.001），以及首次骨骼相关事件时间（16.7 个月 vs. 13.3 个月；风险比，0.69；P<0.001）。恩杂鲁胺组疲劳、腹泻和热潮红的发生率更高。接受恩杂鲁胺治疗的 5 名患者（0.6%）出现癫痫发作。
恩杂鲁胺显著延长了化疗后转移性去势抵抗性前列腺癌男性的生存时间。（由 Medivation 和 Astellas Pharma Global Development 资助；AFFIRM ClinicalTrials.gov 编号，NCT00974311）。
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