Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China.
College of Pharmacy, Fujian Medical University, Fuzhou, China.
Front Immunol. 2022 Sep 14;13:1006860. doi: 10.3389/fimmu.2022.1006860. eCollection 2022.
Immune checkpoint inhibitors (ICIs) in combination withother anti-cancer treatments have been approved for a variety of cancers. While the difference in the incidence of cardiovascular adverse events has not been fully investigated. We aimed to assess the the differences in cardiotoxicity among cancer patients receiving different ICI therapies. PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. websites were searched for all randomized controlled trials (RCTs) of ICI. The primary outcomes were any grade cardiotoxicity and Grade 3-5 cardiotoxicity, the secondary outcomes were any grade myocarditis and Grade 3-5 myocarditis, with sub-analyses based on cancer type and does of ICI. A systematic review and frequency network meta-analysis were then performed for cardiotoxicity events. 91 RCTs (n=52247) involving 12 treatment arms were finally included. We observed that PD-L1 + CTLA-4 had the highest risk among all therapies inducing any grade cardiotoxicity, and the differences were significant except PD-1 + CTLA-4, PD-1 + TTD and PD-L1 + TTD. In addition, CTLA-4 had a higher risk of Grade 3-5 cardiotoxicity than PD-1 and anit-PD-L1. For Grade 1-5 myocarditis and Grade 3-5 myocarditis, no significant difference was found among differences therapies. No differences were observed in subgroup analyses according to does and cancer type. There were differences in the incidence of cardiotoxicity among different ICI therapies. For ICI monotherapy, CTLA-4 may be linked to Grade 3-5 cardiotoxicity than PD-1 or PD-L1. For dual therapy, the cardiotoxicity of dual ICI therapy seems to be higher than that of chemotherapy or targeted therapy.
免疫检查点抑制剂（ICI）与其他抗癌治疗联合已被批准用于多种癌症。虽然心血管不良事件的发生率差异尚未完全研究清楚。我们旨在评估接受不同 ICI 治疗的癌症患者的心脏毒性差异。检索了 PubMed、Embase、Web of Science、Cochrane Library 和 ClinicalTrials.gov 网站上所有 ICI 的随机对照试验（RCT）。主要结局为任何等级的心脏毒性和 3-5 级心脏毒性，次要结局为任何等级心肌炎和 3-5 级心肌炎，并基于癌症类型和 ICI 剂量进行亚分析。然后对心脏毒性事件进行系统评价和频率网络荟萃分析。最终纳入了 91 项 RCT（n=52247）涉及 12 种治疗方案。我们观察到，在所有诱导任何等级心脏毒性的治疗中，PD-L1 + CTLA-4 的风险最高，差异显著，除 PD-1 + CTLA-4、PD-1 + TTD 和 PD-L1 + TTD 外。此外，CTLA-4 的 3-5 级心脏毒性风险高于 PD-1 和抗 PD-L1。对于 1-5 级心肌炎和 3-5 级心肌炎，不同治疗方案之间无显著差异。根据剂量和癌症类型进行亚组分析也未观察到差异。不同的 ICI 治疗方案之间的心脏毒性发生率存在差异。对于 ICI 单药治疗，CTLA-4 可能与 3-5 级心脏毒性相关，而不是 PD-1 或 PD-L1。对于双药治疗，双 ICI 治疗的心脏毒性似乎高于化疗或靶向治疗。
