Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer
Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer
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DOI：
10.1056/nejmoa1903307
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发表时间：
2019-07-04
影响因子：
158.5
通讯作者：
Chowdhury, Simon
中科院分区：
文献类型：
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作者：
Chi, Kim N.;Agarwal, Neeraj;Chowdhury, Simon
背景 Apalutamide 是雄激素受体配体结合域的抑制剂。在转移性去势敏感型前列腺癌患者中，与安慰剂加 ADT 相比，在雄激素剥夺疗法 (ADT) 中加入阿帕鲁胺是否会延长影像学无进展生存期和总生存期尚未确定。方法 在这项双盲 3 期试验中，我们随机分配患有转移性去势敏感前列腺癌的患者接受阿帕鲁胺（每天 240 毫克）或安慰剂，并添加 ADT。允许既往接受过局部疾病治疗和既往多西他赛治疗。主要终点是影像学无进展生存期和总生存期。结果 共有 525 名患者被分配接受阿帕鲁胺加 ADT 治疗，527 名患者被分配接受安慰剂加 ADT 治疗。中位年龄为 68 岁。共有16.4%的患者因局部病变接受过前列腺切除术或接受过放疗，10.7%的患者既往接受过多西他赛治疗； 62.7% 患有高体积疾病，37.3% 患有低体积疾病。在第一次中期分析中，中位随访时间为 22.7 个月，阿帕鲁胺组 24 个月时影像学无进展生存的患者百分比为 68.2%，安慰剂组为 47.5%（影像学进展或死亡的风险比，0.48；95% 置信区间 [CI]，0.39 至 0.60；P
Background Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. Methods In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival. Results A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P