Enzalutamide in metastatic prostate cancer before chemotherapy.
Enzalutamide in metastatic prostate cancer before chemotherapy.
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DOI：
10.1056/nejmoa1405095
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发表时间：
2014-07-31
期刊：
影响因子：
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通讯作者：
PREVAIL Investigators
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作者：
Beer TM;Armstrong AJ;Rathkopf DE;Loriot Y;Sternberg CN;Higano CS;Iversen P;Bhattacharya S;Carles J;Chowdhury S;Davis ID;de Bono JS;Evans CP;Fizazi K;Joshua AM;Kim CS;Kimura G;Mainwaring P;Mansbach H;Miller K;Noonberg SB;Perabo F;Phung D;Saad F;Scher HI;Taplin ME;Venner PM;Tombal B;PREVAIL Investigators
Enzalutamide是一种口服雄激素受体抑制剂，可延长化疗后疾病进展的转移性去势抵抗性前列腺癌男性患者的生存期。对于那些没有接受过化疗的转移性前列腺癌患者，尽管进行了雄激素剥夺治疗，但疾病仍在进展，因此需要新的治疗选择。在这项双盲、III期研究中，我们将1717例患者随机分配接受enzalutamide（剂量为160 mg）或安慰剂每日一次治疗。共同主要终点为放射学无进展生存期和总生存期。在报告了540例死亡后进行的计划中期分析显示积极治疗的益处后，该研究被停止。Enzalutamide治疗患者12个月时的放射学无进展生存率为65%，而安慰剂治疗患者为14%（风险降低81%; Enzalutamide组风险比为0.19; 95%置信区间[CI]为0.15 - 0.23; P<0.001）。Enzalutamide组共有626例患者（72%）在数据截止日期时存活，安慰剂组有532例患者（63%）存活（死亡风险降低29%;风险比为0.71; 95% CI为0.60 - 0.84; P<0.001）。Enzalutamide在所有次要终点（包括至开始细胞毒化疗的时间）方面均显示出获益（风险比，0.35），至第一次发生泌尿系相关事件的时间（风险比，0.72），完全或部分软组织反应（59%对5%），前列腺特异性抗原（PSA）进展的时间（风险比，0.17），以及PSA下降至少50%的比率（78%对3%）（所有比较P<0.001）。疲乏和高血压是Enzalutamide治疗相关的最常见临床相关不良事件。Enzalutamide显著降低了转移性前列腺癌男性的放射学进展和死亡风险，并延迟了化疗的开始。（由Medivation和Astellas Pharma资助; PREVAIL ClinicalTrials.gov编号，NCT 01212991。）
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. 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. 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 the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment. Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.)