PARP抑制剂（PARPi）已成为去势抵抗性转移性前列腺癌（mCRPC）在雄激素受体信号抑制剂（ARSI）治疗失败后的同源重组修复（HRR）缺陷的治疗方法。尽管尚不确定在HRR正常的肿瘤中ARSI + PARPi联合治疗的临床相关性，但已经对新的ARSI + PARPi联合治疗进行了全面测试。为了定量综合评估用于一线治疗mCRPC的PARPi + ARSI联合治疗的疗效和安全性，我们在PubMed、EMBASE、SCOPUS和Cochrane图书馆数据库中搜索了截至2023年2月28日的随机对照试验（RCT）。比较PARPi + ARSI与安慰剂 + ARSI在一线治疗mCRPC中的RCT符合资格。两位审阅员独立进行筛选和数据提取，评估偏见风险，第三位审阅员评估资格标准。总体而言，三个3期RCT纳入了这个系统评价：PROPEL、MAGNITUDE和TALAPRO-2。共有2601名mCRPC患者被纳入。其中2个试验（PROPEL和TALAPRO-2）独立评估了PARPi + ARSI在一线治疗mCRPC中的放射性无进展生存益处，与HRR状态无关。合并风险比为0.62（95%置信区间0.53-0.72）。总体生存期的合并风险比为0.84（95%置信区间0.72-0.98），表明接受该联合治疗的患者死亡风险降低了16%。本次荟萃分析结果支持在无生物标记选择的mCRPC中使用ARSI + PARPi联合治疗。然而，考虑到mCRPC治疗格局的变化，这种联合治疗在HRR正常的癌症中可能具有较低的临床相关性。我们研究了在晚期前列腺癌中测试两类药物（PARP抑制剂和ARSI）联合应用的结果。发现这些组合似乎无论在基因突变中是否被识别为对PARP抑制剂单独治疗的反应标志物都有效。版权所有 © 2023，由Elsevier B.V.出版。

PARP inhibitors (PARPi) are established treatments for metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) deficiency after androgen receptor signalling inhibitor (ARSI) failure. New PARPi + ARSI combinations have been tested in all comers, although their clinical relevance in HRR-proficient tumours remains uncertain.To quantitatively synthesise evidence from randomised trials assessing the efficacy and safety of PARPi + ARSI combinations for first-line treatment of mCRPC.We searched the PubMed, EMBASE, SCOPUS, and Cochrane Library databases up to February 28, 2023. Randomised controlled trials (RCTs) comparing PARPi + ARSI versus placebo + ARSI for first-line treatment of mCRPC were eligible. Two reviewers independently performed screening and data extraction and assessed the risk of bias, while a third reviewer evaluated the eligibility criteria.Overall, three phase 3 RCTs were included in the systematic review: PROPEL, MAGNITUDE, and TALAPRO-2. A total of 2601 patients with mCRPC were enrolled. Two of these trials (PROPEL and TALAPRO-2) assessed the radiographic progression-free survival benefit of PARPi + ARSI for first-line treatment of mCRPC, independent of HRR status. The pooled hazard ratio was 0.62 (95% confidence interval 0.53-0.72). The pooled hazard ratio for overall survival was 0.84 (95% confidence interval 0.72-0.98), indicating a 16% reduction in the risk of death among patients who received the combination.Results from this meta-analysis support the use of ARSI + PARPi combinations in biomarker-unselected mCRPC. However, such combinations might be less clinically relevant in HRR-proficient cancers, especially considering the change in treatment landscape for mCRPC.We looked at outcomes from trials testing combinations of two classes of drugs (PARP inhibitors and ARSI) in advanced prostate cancer. We found that these combinations seem to work regardless of gene mutations identified as biomarkers of response to PARP inhibitors when used on their own.Copyright © 2023. Published by Elsevier B.V.