Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months.
UNASSIGNED: PROSPERO (CRD42022385274).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months.
UNASSIGNED: PROSPERO (CRD42022385274).
摘要：
■本研究旨在评估PARP抑制剂（PARPis）的毒性，基于随机对照试验（RCT）和FDA不良事件报告系统（FAERS）数据库。
■从开始到2024年4月16日搜索了四个电子数据库，以查找已批准的PARPis的RCT。主要和次要结局是3-5级不良事件（AE）和3-5级血液学AE，分别。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）。进行不成比例性分析以估计来自FAERS数据库的与PARPis相关的血液学AE的信号。
■总的来说，包括27个RCTs，涉及11,067例癌症患者。在四个批准的PARPis中，Olaparib对任何3-5级AE和血液学AE的安全性最好。奥拉帕尼没有增加血小板减少症的风险（RR：1.48;95CI：0.64-3.39），但是其他PARPis做到了。此外，在FAERS数据库中发现了14,780例与PARPis相关的血液学不良事件报告，所有PARPis均与强烈的血液学AE信号相关。血液学AE主要发生在PARPi开始后的前3个月内（80.84%）。
■在5种PARPis中，Olaparib的安全性最好。PARPi相关血液学AE主要发生在前3个月内。
■PROSPERO（CRD420223885274）。
■从开始到2024年4月16日搜索了四个电子数据库，以查找已批准的PARPis的RCT。主要和次要结局是3-5级不良事件（AE）和3-5级血液学AE，分别。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）。进行不成比例性分析以估计来自FAERS数据库的与PARPis相关的血液学AE的信号。
■总的来说，包括27个RCTs，涉及11,067例癌症患者。在四个批准的PARPis中，Olaparib对任何3-5级AE和血液学AE的安全性最好。奥拉帕尼没有增加血小板减少症的风险（RR：1.48;95CI：0.64-3.39），但是其他PARPis做到了。此外，在FAERS数据库中发现了14,780例与PARPis相关的血液学不良事件报告，所有PARPis均与强烈的血液学AE信号相关。血液学AE主要发生在PARPi开始后的前3个月内（80.84%）。
■在5种PARPis中，Olaparib的安全性最好。PARPi相关血液学AE主要发生在前3个月内。
■PROSPERO（CRD420223885274）。
