Background: Poly ADP-ribose polymerase inhibitors (PARPis) are an important class of therapeutics for metastatic castration-resistant prostate cancer (mCRPC). Unlike hormone-based treatments for mCRPC, PARPis are not without drug-related hematological adverse events. Objective: To review the evidence on hematological toxicities, including anemia, thrombocytopenia, and neutropenia from PARPis in prostate cancer. Study Methodology: A systematic review and meta-analysis using the PRISMA guidelines was performed for phase II and III randomized controlled trials (RCTs) of PARPis in prostate cancer. PubMed, Embase, and Ovid All EBM reviews—Cochrane were queried from inception to 9 June 2023. The Mantel–Haenszel method was used to report risk ratios (RR) and 95% confidence intervals (CI) for all-grade and high-grade anemia, thrombocytopenia, and neutropenia toxicities. Results: The systematic review retrieved eight phase II and III RCTs; specifically, eight were included in the anemia, five in the all-grade thrombocytopenia and neutropenia, and four in the high-grade thrombocytopenia and neutropenia outcomes. Compared to a placebo and/or other non-PARPi treatments, PARPi use was associated with an increased risk of all-grade anemia (RR, 3.37; 95% CI, 2.37–4.79;p< 0.00001), thrombocytopenia (RR, 4.54; 95% CI, 1.97–10.44;p= 0.0004), and neutropenia (RR, 3.11; 95% CI, 1.60–6.03;p= 0.0008). High-grade anemia (RR, 6.94; 95% CI, 4.06–11.86;p< 0.00001) and thrombocytopenia (RR, 5.52; 95% CI, 2.80–10.88;p< 0.00001) were also associated with an increased risk, while high-grade neutropenia (RR, 3.63; 95% CI, 0.77–17.23;p= 0.10) showed no significant association. Subgroup stratification analyses showed differences in various all-grade and high-grade toxicities. Conclusion: PARPis were associated with an increased risk of hematological AEs. Future studies with more pooled RCTs will enhance this understanding and continue to inform patient–physician shared decision-making. Future studies may also have a role in improving the current management strategies for these AEs.
背景：聚腺苷二磷酸核糖聚合酶抑制剂（PARPis）是治疗转移性去势抵抗性前列腺癌（mCRPC）的重要药物类别。与基于激素的mCRPC治疗不同，PARPis并非没有药物相关的血液学不良事件。目的：综述PARPis在前列腺癌治疗中引起血液学毒性（包括贫血、血小板减少和中性粒细胞减少）的证据。研究方法：采用PRISMA指南对前列腺癌PARPis的II期和III期随机对照试验（RCTs）进行系统综述和荟萃分析。检索了PubMed、Embase和Ovid All EBM reviews—Cochrane数据库自建库至2023年6月9日的文献。使用Mantel–Haenszel方法报告所有级别和高级别贫血、血小板减少及中性粒细胞减少毒性的风险比（RR）和95%置信区间（CI）。结果：系统综述共纳入8项II期和III期RCTs；具体而言，8项研究纳入贫血结局分析，5项纳入所有级别血小板减少和中性粒细胞减少结局分析，4项纳入高级别血小板减少和中性粒细胞减少结局分析。与安慰剂和/或其他非PARPi治疗相比，使用PARPi与所有级别贫血（RR, 3.37; 95% CI, 2.37–4.79; p < 0.00001）、血小板减少（RR, 4.54; 95% CI, 1.97–10.44; p = 0.0004）和中性粒细胞减少（RR, 3.11; 95% CI, 1.60–6.03; p = 0.0008）的风险增加相关。高级别贫血（RR, 6.94; 95% CI, 4.06–11.86; p < 0.00001）和血小板减少（RR, 5.52; 95% CI, 2.80–10.88; p < 0.00001）也与风险增加相关，而高级别中性粒细胞减少（RR, 3.63; 95% CI, 0.77–17.23; p = 0.10）未显示显著关联。亚组分层分析显示不同级别毒性存在差异。结论：PARPis与血液学不良事件风险增加相关。未来纳入更多RCTs的汇总研究将深化这一认识，并持续为医患共同决策提供信息。未来研究也可能对改进当前这些不良事件的管理策略发挥作用。
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