Academic Trials Promoting Team, Institut Jules Bordet, L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium; Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center - IRCCS, Humanitas Cancer Center, via Manzoni 56, 20089, Rozzano, Milan, Italy; Humanitas University, Department of Biomedical Sciences, via Rita Levi Montalcini 4, 20090 Pieve Emanuele - Milan, Italy.
Academic Trials Promoting Team, Institut Jules Bordet, L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium.
Eur J Cancer. 2021 May;148:76-91. doi: 10.1016/j.ejca.2021.01.043. Epub 2021 Mar 16.
Immune checkpoint inhibitors (ICIs) may cause potentially life-threatening adverse events (AEs), but the risk of cardiotoxicity has not been fully investigated. It is also unknown whether ICI combinations increase cardiotoxicity compared with single ICI. We aimed to assess the cardiotoxicity of ICI in a range of tumour types.
This systematic review and meta-analysis was conducted according to PRISMA guidelines (PROSPERO registration number: CRD42020183524). A systematic search of PubMed, MEDLINE, Embase databases, and conference proceedings was performed up to 30 June 2020. All randomised clinical trials comparing ICI with other treatments (primary objective) or dual-agent ICI versus single-agent ICI (secondary objective) in any solid tumour were included. Pooled risk ratios (RRs) with 95% confidence intervals (95% CIs) for cardiotoxicity events were calculated using random effect models.
Eighty studies including 35,337 patients were included in the analysis (66 studies with 34,664 patients for the primary endpoint and 14 studies with 673 patients for the secondary endpoint). No significant differences in terms of cardiac AEs were observed between ICI and non-ICI groups (RR 1.14, 95% CI 0.88-1.48, p = 0.326) nor between dual ICI and single ICI groups (RR 1.91, 95% CI 0.52-7.01, p = 0.329). Myocarditis incidence did not significantly differ between ICI and non-ICI groups (RR 1.11, 95% CI 0.64-1.92, p = 0.701) nor between dual ICI and single ICI groups (RR 1.10, 95% CI 0.31-3.87, p = 0.881). No differences were observed in subgroup analyses according to tumour type, setting of disease, treatment line, and type of treatment.
The use of ICI as single or combination regimens is not associated with increased risk of cardiotoxicity.
免疫检查点抑制剂（ICI）可能会引发危及生命的不良反应（AE），但尚未充分研究其发生心脏毒性的风险。也不清楚与单药ICI 相比，ICI 联合用药是否会增加心脏毒性。我们旨在评估多种肿瘤类型中 ICI 的心脏毒性。
本系统评价和荟萃分析根据 PRISMA 指南（PROSPERO 注册号：CRD42020183524）进行。系统检索了 PubMed、MEDLINE、Embase 数据库和会议记录，检索时间截至 2020 年 6 月 30 日。纳入了比较 ICI 与其他治疗方法（主要终点）或双药 ICI 与单药 ICI（次要终点）治疗任何实体瘤的随机临床试验。采用随机效应模型计算心脏毒性事件的汇总风险比（RR）及其 95%置信区间（95%CI）。
共纳入 80 项研究，包括 35337 例患者（66 项研究的 34664 例患者用于主要终点，14 项研究的 673 例患者用于次要终点）。ICI 组与非 ICI 组之间的心脏 AE 无显著差异（RR 1.14，95%CI 0.88-1.48，p=0.326），也无双药 ICI 组与单药 ICI 组之间的差异（RR 1.91，95%CI 0.52-7.01，p=0.329）。ICI 组与非 ICI 组的心肌炎发生率无显著差异（RR 1.11，95%CI 0.64-1.92，p=0.701），也无双药 ICI 组与单药 ICI 组之间的差异（RR 1.10，95%CI 0.31-3.87，p=0.881）。根据肿瘤类型、疾病设置、治疗线和治疗类型进行的亚组分析均未见差异。
ICI 单药或联合方案的使用与心脏毒性风险增加无关。
