4.6 Article

Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study

期刊

EUROPEAN UROLOGY
卷 83, 期 1, 页码 15-26

出版社

ELSEVIER
DOI: 10.1016/j.eururo.2022.08.005

关键词

Metastatic castration-resistant; prostate cancer; Olaparib; Pembrolizumab

向作者/读者索取更多资源

This study evaluated the efficacy and safety of pembrolizumab plus olaparib in previously treated patients with metastatic castration-resistant prostate cancer. The results demonstrated antitumor activity and expected safety of this combination therapy in patients.
Background: Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC).Objective: To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC.Design, setting, and participants: Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose dis-ease progressed within 6 mo of screening. Intervention: Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily.Outcome measurements and statistical analysis: The primary endpoints were safety, con-firmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS).Results and limitations: Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65-76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22-47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0-6.5) and median OS was 14 mo (95% CI, 10.4-18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1) -positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3-5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design.Conclusions: Pembrolizumab plus olaparib had a safety profile consistent with the pro-files of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC.Patient summary: Pembrolizumab plus olaparib showed antitumor activity and expected safety in patients with metastatic castration-resistant prostate cancer.(c) 2022 Merck Sharp & Dohme LLC., a subsidiary Merck & Co., Inc., Rahway, NJ, USA and The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据