Safety and hematological toxicities of PARP inhibitors in patients with cancer: a systematic review of randomized controlled trials and a pharmacovigilance analysis.

IF 2.9 3区医学 Q2 ONCOLOGY

Expert Review of Anticancer Therapy Pub Date : 2024-07-01 Epub Date: 2024-05-23 DOI:10.1080/14737140.2024.2357822

Meng-Fei Dai, Xin Wang, Wen-Xiu Xin, Si-Si Kong, Wei-Ben Xu, Hai-Ying Ding, Luo Fang

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引用次数: 0

Abstract

Introduction: This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database.

Methods: Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database.

Results: Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation.

Conclusion: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months.

Registration: PROSPERO (CRD42022385274).

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PARP 抑制剂对癌症患者的安全性和血液学毒性：随机对照试验的系统回顾和药物警戒分析。

简介：本研究旨在根据随机对照试验（RCTs）和美国食品药品管理局不良事件报告系统（FAERS）数据库估算 PARP 抑制剂（PARPis）的毒性：本研究旨在根据随机对照试验（RCT）和美国食品及药物管理局不良事件报告系统（FAERS）数据库估算PARP抑制剂（PARPis）的毒性：方法：在四个电子数据库中检索了从开始到 2024 年 4 月 16 日期间批准的 PARPis 的 RCT。主要和次要结果分别为 3-5 级不良事件（AEs）和 3-5 级血液学 AE。我们进行了网络荟萃分析，以计算结果的相对风险 (RR) 和 95% 置信区间 (CI)。我们还进行了一项比例失调分析，以估算FAERS数据库中与PARPis相关的血液学AE的信号：结果：共纳入了27项RCT，涉及11067名癌症患者。在已获批的四种PARPis中，奥拉帕利在3-5级AE和血液学AE方面的安全性最好。奥拉帕利不会增加血小板减少症的风险（RR：1.48；95%CI：0.64-3.39），但其他 PARPis 则会。此外，FAERS数据库中还发现了14780份与PARPis相关的血液学AE报告，所有PARPis都与强烈的血液学AE信号相关。血液学AE主要发生在开始使用PARPi后的头3个月内（80.84%）：结论：在五种PARPi中，奥拉帕利的安全性最好。结论：在五种PARP中，奥拉帕利的安全性最好：PROCROPERO（CRD42022385274）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Anticancer Therapy 医学-肿瘤学

CiteScore

5.10

自引率

3.00%

发文量

100

审稿时长

4-8 weeks

期刊介绍： Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches. Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care. Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections: Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results Article Highlights – an executive summary of the author’s most critical points.