Pembrolizumab plus enzalutamide versus placebo plus enzalutamide for chemotherapy-naive metastatic castration-resistant prostate cancer: the randomized, double-blind, phase III KEYNOTE-641 study.

The randomized, double-blind, phase III KEYNOTE-641 study evaluated pembrolizumab plus enzalutamide versus placebo plus enzalutamide in participants with chemotherapy-naive mCRPC.

随机、双盲、III期KEYNOTE-641研究评估了帕博利珠单抗联合恩杂鲁胺与安慰剂联合恩杂鲁胺在化疗未经治疗的mCRPC患者中的效果。

patients_and_methods

Eligible participants were males aged ≥18 years with confirmed mCRPC and no prior chemotherapy except docetaxel in the hormone-sensitive setting.

符合条件的参与者为年龄≥18岁的男性，确诊为转移性去势抵抗性前列腺癌（mCRPC），且在激素敏感环境下未接受过除多西他赛以外的化疗。

Prior abiraterone treatment was permitted.

允许接受过阿比特龙治疗的患者参与。

Participants were randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo intravenously once every 3 weeks for ≤35 cycles plus enzalutamide 160 mg orally daily.

参与者被随机1:1分配，接受每3周一次静脉注射200毫克帕博利珠单抗或安慰剂，最多35个周期，同时每天口服160毫克恩杂鲁胺。

Dual primary end points were overall survival(OS) and radiographic progression-free survival(rPFS) per Prostate Cancer Clinical Trials Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review.

双重主要终点是总生存（OS）和根据前列腺癌临床试验工作组（PCWG）修改的实体瘤反应评估标准（RECIST v1.1）进行的盲法独立中央审查的放射学无进展生存（rPFS）。

Safety was a secondary end point.

安全性是一个次要终点。

Results

Between 21 August 2019, and 10 June 2022, 1244 participants were randomly assigned to pembrolizumab plus enzalutamide (n = 621) or placebo plus enzalutamide (n = 623).

在2019年8月21日至2022年6月10日期间，共有1244名参与者被随机分配至帕博利珠单抗加恩杂鲁胺组（n = 621）或安慰剂加恩杂鲁胺组（n = 623）。

At the data cut-off date (12 December 2022), median follow-up was 27.6 months (range, 6.1-39.8 months).

截至数据截止日期（2022年12月12日），中位随访时间为27.6个月（范围，6.1-39.8个月）。

Primary end points of OS [median, 24.7 versus 27.3 months; hazard ratio(HR) 1.04, 95% confidence interval(CI) 0.88-1.22, P = 0.66] and rPFS (median, 10.4 versus 9.0 months; HR 0.98, 95% CI 0.84-1.14, P = 0.41) with pembrolizumab plus enzalutamide versus placebo plus enzalutamide were not met.

主要终点指标总生存期（OS）[中位数，24.7个月对比27.3个月；风险比（HR）1.04，95%置信区间（CI）0.88-1.22，P = 0.66]和放射学无进展生存期（rPFS）（中位数，10.4个月对比9.0个月；HR 0.98，95% CI 0.84-1.14，P = 0.41）使用帕博利珠单抗加恩杂鲁胺对比安慰剂加恩杂鲁胺均未达到。

The prespecified boundary for futility for OS was crossed, and the study was stopped.

预先设定的总生存期（OS）无益性边界已被跨越，研究因此停止。

Grade ≥3 treatment-related adverse events occurred in 192 of 615 participants (31.2%) with one or more doses of pembrolizumab plus enzalutamide and in 67 of 620 participants (10.8%) with one or more doses of placebo plus enzalutamide.

在615名接受帕博利珠单抗加恩杂鲁胺治疗的参与者中，有192人（31.2%）出现3级或更高级别的治疗相关不良事件，而在620名接受安慰剂加恩杂鲁胺治疗的参与者中，有67人（10.8%）出现3级或更高级别的治疗相关不良事件。

Seventy-one (11.5%) and 21 (3.4%) participants, respectively, discontinued study treatment due to treatment-related adverse events.

分别有71名（11.5%）和21名（3.4%）的参与者因治疗相关不良事件而中断了研究治疗。

Conclusions

Adding pembrolizumab to enzalutamide did not improve efficacy outcomes for participants with chemotherapy-naive mCRPC.

将派姆单抗添加到恩杂鲁胺中，并没有改善化疗未经治疗的转移性去势抵抗性前列腺癌（mCRPC）参与者的疗效结果。

Additional toxicity was observed with the combination regimen.

观察到联合方案的额外毒性。