Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Department of Medical Oncology, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Target Oncol. 2024 Jan;19(1):1-11. doi: 10.1007/s11523-023-01016-x. Epub 2023 Nov 22.
PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically relevant adverse effect of these agents is hematological toxicity, a typical class adverse event (AE), which can lead to treatment modifications and discontinuations.
We aimed to analyze the risk of hematological AEs, including anemia, neutropenia, and thrombocytopenia secondary to PARPi treatments in mCRPC.
This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We systematically searched the PubMed, EMBASE, and Cochrane databases, the American Society of Clinical Oncology (ASCO), and the European Society of Medical Oncology (ESMO) meeting abstracts for clinical trials concerning the use of PARPis, both as single agents and in combination, in patients with mCRPC. The search deadline was 30 June, 2023. We analyzed the pooled incidence of all grades of and ≥ G3 anemia, neutropenia, and thrombocytopenia. We subsequently calculated risk ratios (RRs) for all grades of and ≥ G3 AEs of PARPis versus non-PARPis from randomized clinical trials (RCTs).
Eleven phase 2/3 trials with olaparib, niraparib, rucaparib, and talazoparib administered as single agents or combined with ARTA were selected. Anemia was the most common all grades (38.6%) and ≥ G3 AE (24.9%). In the analysis of relative risk, six RCTs were included. The administration of PARPis significantly increased the risk of developing all grades of anemia (RR = 2.44), neutropenia (RR = 3.15), and thrombocytopenia (RR = 4.66) compared with non-PARPis. Similarly, a significant increase in the risk of ≥ G3 anemia (RR = 5.73) and thrombocytopenia (RR = 5.44), and a not significant increased risk of neutropenia (RR = 3.41), were detected.
In mCRPC, PARPis increase the risk of hematological toxicity compared with other treatments, both as single agents or combined with ARTA (high-quality evidence). Clinicians should be aware of this risk and the correct management, especially with the expected increased PARPis use in mCRPC.
聚腺苷二磷酸核糖聚合酶抑制剂（PARPi）作为单一药物或与雄激素受体靶向药物（ARTA）联合使用，是转移性去势抵抗性前列腺癌（mCRPC）患者的有效治疗选择。然而，这些药物的一个临床相关的不良反应是血液学毒性，这是一种典型的药物不良反应（AE），可导致治疗方式的改变和药物的停止使用。
我们旨在分析 PARPi 治疗 mCRPC 导致的血液学不良反应（包括贫血、中性粒细胞减少症和血小板减少症）的风险。
本系统评价和荟萃分析遵循了系统评价和荟萃分析的首选报告项目（PRISMA）声明。我们系统地检索了 PubMed、EMBASE 和 Cochrane 数据库、美国临床肿瘤学会（ASCO）和欧洲肿瘤内科学会（ESMO）会议摘要，以查找关于 PARPi 单药或联合用于 mCRPC 患者的临床试验。检索截止日期为 2023 年 6 月 30 日。我们分析了所有级别和≥G3 贫血、中性粒细胞减少症和血小板减少症的总发生率。随后，我们从随机临床试验（RCT）中计算了 PARPi 与非 PARPi 治疗所有级别和≥G3 AE 的风险比（RR）。
选择了 11 项奥拉帕利、尼拉帕利、鲁卡帕利和他拉唑帕利作为单药或联合 ARTA 治疗的 2/3 期试验。贫血是最常见的所有级别（38.6%）和≥G3 AE（24.9%）。在相对风险分析中，纳入了 6 项 RCT。与非 PARPi 相比，PARPi 的治疗显著增加了所有级别贫血（RR=2.44）、中性粒细胞减少症（RR=3.15）和血小板减少症（RR=4.66）的发生风险。同样，也显著增加了≥G3 贫血（RR=5.73）和血小板减少症（RR=5.44）的发生风险，以及中性粒细胞减少症的风险增加但无统计学意义（RR=3.41）。
在 mCRPC 中，PARPi 与其他治疗方法相比，无论是单药治疗还是与 ARTA 联合治疗，都会增加血液学毒性的风险（高质量证据）。临床医生应意识到这一风险以及正确的管理方法，特别是在预计 mCRPC 中 PARPi 使用增加的情况下。
