Pembrolizumab plus enzalutamide and androgen deprivation therapy versus placebo plus enzalutamide and androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: the randomized, double-blind, phase III KEYNOTE-991 study.

The placebo-controlled, double-blind, phase III KEYNOTE-991 study evaluated the efficacy and safety of adding pembrolizumab to enzalutamide and androgen deprivation therapy (ADT) in participants with mHSPC.

安慰剂对照、双盲、III期KEYNOTE-991研究评估了在mHSPC患者中加用派姆单抗至恩杂鲁胺和雄激素剥夺治疗（ADT）的疗效和安全性。

patients_and_methods

Eligible participants were aged ≥18 years with next-generation hormonal agent-naive mHSPC.

符合条件的参与者年龄≥18岁，且为新一代激素药物未经治疗的转移性激素敏感性前列腺癌（mHSPC）患者。

Participants were randomly assigned (1 : 1) to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for ≤35 cycles, with oral enzalutamide 160 mg and continuous ADT.

参与者按1:1的比例随机分配，接受静脉注射帕博利珠单抗200毫克或安慰剂，每3周一次，最多35个周期，同时口服恩杂鲁胺160毫克和持续的雄激素剥夺治疗（ADT）。

Primary endpoints were radiographic progression-free survival(rPFS) and overall survival(OS).

主要终点是放射影像无进展生存期（rPFS）和总生存（OS）。

Safety was a secondary endpoint.

安全性是次要终点。

Results

Between 2 March 2020 and 9 August 2021, 626 participants were randomly assigned to receive pembrolizumab plus enzalutamide and ADT and 625 participants to receive placebo plus enzalutamide and ADT.

在2020年3月2日至2021年8月9日期间，626名参与者被随机分配接受pembrolizumab联合enzalutamide和ADT治疗，另外625名参与者被随机分配接受安慰剂联合enzalutamide和ADT治疗。

At the first interim analysis, the median follow-up was 21.1 months (range 14.8-32.0 months). rPFS was not superior with pembrolizumab versus placebo [median not reached in both arms; hazard ratio(HR) 1.20, 95% confidence interval(CI) 0.96-1.49, P = 0.9467].

在第一次中期分析中，中位随访时间为21.1个月（范围14.8-32.0个月）。与安慰剂相比，pembrolizumab并未显示出更好的rPFS[两组均未达到中位数；风险比（HR）1.20，95%置信区间（CI）0.96-1.49，P = 0.9467]。

Median OS was not reached in either arm (HR 1.16, 95% CI 0.88-1.53; not formally statistically tested as per the multiplicity strategy).

在任一组中，中位总生存期均未达到（风险比1.16，95% 置信区间 0.88-1.53；根据多重性策略，未正式进行统计学检验）。

Grade ≥3 adverse events (AEs) and serious AEs (SAEs) were reported in 61.9% versus 38.1% and 40.3% versus 23.2% of participants in the pembrolizumab versus the placebo arm, respectively.

在帕博利珠单抗组与安慰剂组中，分别有61.9%和38.1%的参与者报告了3级或以上的不良事件（不良事件），以及40.3%和23.2%的参与者报告了严重不良事件（严重不良事件）。

Any-grade rash occurred at a higher frequency with pembrolizumab (25.1%) versus placebo (9.3%).

与安慰剂（9.3%）相比，帕博利珠单抗治疗中任何级别的皮疹发生频率更高（25.1%）。

Conclusions

KEYNOTE-991 did not meet its primary endpoint and was stopped for futility.

KEYNOTE-991未达到其主要终点，并因无效而停止。

The addition of pembrolizumab to enzalutamide and ADT was associated with higher frequencies of grade ≥3 AEs and SAEs than with placebo.

将帕博利珠单抗加入恩杂鲁胺和雄激素剥夺治疗（ADT）与安慰剂相比，与更高频率的3级或更高级别的不良事件（AEs）和严重不良事件（SAEs）相关。

Rash was identified as an additional safety signal with pembrolizumab plus enzalutamide and ADT.

与帕博利珠单抗联合恩杂鲁胺和ADT治疗相关的额外安全信号被识别为皮疹。