Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
Current Address: University of Minnesota Masonic Cancer Center, Minneapolis, MN.
J Clin Oncol. 2023 Aug 1;41(22):3839-3850. doi: 10.1200/JCO.23.00233. Epub 2023 Jun 8.
There is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) for biomarker-unselected, previously treated mCRPC.
Eligible participants had mCRPC that progressed on or after abiraterone or enzalutamide (but not both) and docetaxel. Participants were randomly assigned (2:1) to pembrolizumab plus olaparib or NHA (abiraterone or enzalutamide). The dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group-modified RECIST 1.1 and overall survival (OS). Time to first subsequent therapy (TFST) was a key secondary end point. Safety and objective response rate (ORR) were secondary end points.
Between May 30, 2019, and July 16, 2021, 529 participants were randomly assigned to pembrolizumab plus olaparib and 264 to NHA. At final rPFS analysis, median rPFS was 4.4 months (95% CI, 4.2 to 6.0) with pembrolizumab plus olaparib and 4.2 months (95% CI, 4.0 to 6.1) with NHA (hazard ratio [HR], 1.02 [95% CI, 0.82 to 1.25]; = .55). At final OS analysis, median OS was 15.8 months (95% CI, 14.6 to 17.0) and 14.6 months (95% CI, 12.6 to 17.3), respectively (HR, 0.94 [95% CI, 0.77 to 1.14]; = .26). At final TFST analysis, median TFST was 7.2 months (95% CI, 6.7 to 8.1) versus 5.7 months (95% CI, 5.0 to 7.1), respectively (HR, 0.86 [95% CI, 0.71 to 1.03]). ORR was higher with pembrolizumab plus olaparib versus NHA (16.8% 5.9%). Grade ≥3 treatment-related adverse events occurred in 34.6% and 9.0% of participants, respectively.
Pembrolizumab plus olaparib did not significantly improve rPFS or OS versus NHA in participants with biomarker-unselected, heavily pretreated mCRPC. The study was stopped for futility. No new safety signals occurred.
对于经过大量预处理的转移性去势抵抗性前列腺癌（mCRPC）患者，需要有延长生存期的治疗选择。III 期、开放性 KEYLYNK-010 研究评估了帕博利珠单抗联合奥拉帕利与下一代激素药物（NHA）用于未经生物标志物选择的、先前治疗过的 mCRPC。
符合条件的参与者患有 mCRPC，在接受阿比特龙或恩扎鲁胺（但不是两者）和多西他赛治疗后进展。参与者被随机分配（2:1）接受帕博利珠单抗联合奥拉帕利或 NHA（阿比特龙或恩扎鲁胺）。盲法独立中央审查根据前列腺癌工作组修改的 RECIST 1.1 评估的放射学无进展生存期（rPFS）和总生存期（OS）是双重主要终点。首次后续治疗时间（TFST）是关键次要终点。安全性和客观缓解率（ORR）是次要终点。
2019 年 5 月 30 日至 2021 年 7 月 16 日期间，529 名参与者被随机分配至帕博利珠单抗联合奥拉帕利组，264 名参与者被随机分配至 NHA 组。在最终 rPFS 分析时，帕博利珠单抗联合奥拉帕利组的中位 rPFS 为 4.4 个月（95%CI，4.2 至 6.0），NHA 组为 4.2 个月（95%CI，4.0 至 6.1）（风险比[HR]，1.02[95%CI，0.82 至 1.25]；=0.55）。在最终 OS 分析时，中位 OS 分别为 15.8 个月（95%CI，14.6 至 17.0）和 14.6 个月（95%CI，12.6 至 17.3）（HR，0.94[95%CI，0.77 至 1.14]；=0.26）。在最终 TFST 分析时，中位 TFST 分别为 7.2 个月（95%CI，6.7 至 8.1）和 5.7 个月（95%CI，5.0 至 7.1）（HR，0.86[95%CI，0.71 至 1.03]）。帕博利珠单抗联合奥拉帕利组的 ORR 高于 NHA 组（16.8% 5.9%）。分别有 34.6%和 9.0%的参与者发生≥3 级治疗相关不良事件。
在未经生物标志物选择的、经过大量预处理的 mCRPC 患者中，与 NHA 相比，帕博利珠单抗联合奥拉帕利并未显著改善 rPFS 或 OS。该研究因无效而停止。没有新的安全信号。
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