多聚（ADP-核糖）聚合酶抑制剂在转移性去势抵抗性前列腺癌患者中的应用：一项随机对照试验的荟萃分析。
Poly (ADP-ribose) Polymerase Inhibitors in Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials.
机构信息
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430030, China.
出版信息
Medicina (Kaunas). 2023 Dec 18;59(12):2198. doi: 10.3390/medicina59122198.
: Several recent randomized controlled trials (RCTs) have reported on the survival benefits of poly (ADP-ribose) polymerase inhibitors (PARPi) compared to standard-of-care (SOC) treatment (enzalutamide, abiraterone, or docetaxel) in patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is a limited integrated analysis of high-quality evidence comparing the efficacy and safety of PARPi and SOC treatments in this context. : This study aims to comprehensively analyze the survival benefits and adverse events associated with PARPi and SOC treatments through a head-to-head meta-analysis in mCRPC. : A systematic review search was conducted in PubMed, Embase, Clinical trials, and the Central Cochrane Registry in July 2023. RCTs were assessed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The systematic review was prospectively registered on PROSPERO (CRD42023441034). : A total of 8 studies, encompassing 2341 cases in the PARPi treatment arm and 1810 cases in the controlled arm, were included in the qualitative synthesis. The hazard ratio (HR) for radiographic progression-free survival (rPFS) and overall survival (OS) were 0.74 (95% CI, 0.61-0.90) and 0.89 (95% CI, 0.80-0.99), respectively, in the intention-to-treatment patients. For subgroup analysis, HRs for rPFS and OS in the BRCA-mutated subgroup were 0.39 (95% CI, 0.28-0.55) and 0.62 (95% CI, 0.38-0.99), while in the HRR-mutated subgroup, HR for rPFS was 0.57 (95% CI, 0.48-0.69) and for OS was 0.77 (95% CI, 0.64-0.93). The odds ratio (OR) for all grades of adverse events (AEs) and AEs with severity of at least grade 3 were 3.86 (95% CI, 2.53-5.90) and 2.30 (95% CI, 1.63-3.26), respectively. : PARP inhibitors demonstrate greater effectiveness than SOC treatments in HRR/BRCA-positive patients with mCRPC. Further research is required to explore ways to reduce adverse event rates and investigate the efficacy of HRR/BRCA-negative patients.
几种最近的随机对照试验（RCT）报告了聚（ADP-核糖）聚合酶抑制剂（PARPi）与转移性去势抵抗性前列腺癌（mCRPC）患者的标准治疗（恩扎鲁胺、阿比特龙或多西他赛）相比的生存获益。然而，在这种情况下，对 PARPi 和 SOC 治疗的疗效和安全性进行高证据质量综合分析的研究有限。
本研究旨在通过 mCRPC 的头对头荟萃分析全面分析 PARPi 和 SOC 治疗的生存获益和不良事件。
2023 年 7 月，在 PubMed、Embase、临床试验和 Cochrane 中心注册库中进行了系统评价检索。根据系统评价和荟萃分析的首选报告项目（PRISMA）指南评估 RCT。系统评价前瞻性地在 PROSPERO（CRD42023441034）上注册。
定性综合分析纳入了 8 项研究，PARPi 治疗组纳入 2341 例，对照组纳入 1810 例。意向治疗患者的放射进展无进展生存期（rPFS）和总生存期（OS）的风险比（HR）分别为 0.74（95%CI，0.61-0.90）和 0.89（95%CI，0.80-0.99）。对于亚组分析，BRCA 突变亚组的 rPFS 和 OS 的 HR 分别为 0.39（95%CI，0.28-0.55）和 0.62（95%CI，0.38-0.99），而 HRR 突变亚组的 rPFS 的 HR 为 0.57（95%CI，0.48-0.69），OS 的 HR 为 0.77（95%CI，0.64-0.93）。所有级别不良事件（AE）和至少 3 级严重程度的 AE 的优势比（OR）分别为 3.86（95%CI，2.53-5.90）和 2.30（95%CI，1.63-3.26）。
PARPi 抑制剂在 HRR/BRCA 阳性 mCRPC 患者中的疗效优于 SOC 治疗。需要进一步研究以探索降低不良事件发生率的方法，并研究 HRR/BRCA 阴性患者的疗效。
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