Hu Jiexuan, Tian Ruyue, Ma Yingjie, Zhen Hongchao, Ma Xiao, Su Qiang, Cao Bangwei
Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Department of Ultrasound, Aero Space Central Hospital, Beijing, China.
Front Oncol. 2021 May 27;11:645245. doi: 10.3389/fonc.2021.645245. eCollection 2021.
We performed a systematic review and meta-analysis to evaluate the risks of cardiac adverse events in solid tumor patients treated with monotherapy of immune checkpoint inhibitors (ICIs) or combined therapy of ICIs plus chemotherapy.
Eligible studies were selected through the following databases: PubMed, Embase and clinical trials (https://clinicaltrials.gov.) and included phase III/IV randomized controlled trials (RCTs) involving patients with the solid tumor treated with ICIs. The data was analyzed by using Review Manager (version5.3), Stata (version 15.1).
Among 2,551 studies, 25 clinical trials including 20,244 patients were qualified for the meta-analysis. Compared with PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy showed significant increase in grade 5 arrhythmology (OR 3.90, 95% CI: 1.08-14.06, p = 0.603). PD-1 inhibitor plus chemotherapy show significant increase in grades 1-5 myocardial disease (OR 5.09, 95% CI: 1.11-23.32, p = 1.000). Compared with chemotherapy, PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy show significant increase in grades 1-5 arrhythmology (OR 2.49, 95% CI: 1.30-4.78, p = 0.289).
Our meta-analysis demonstrated that PD-1 inhibitor plus CTLA-4 inhibitor can result in a higher risk of grade 5 arrhythmology in comparison with PD-1/CTLA-4 inhibitor alone, and a higher risk of grade 5 arrhythmology in comparison with chemotherapy. PD-1 inhibitor plus chemotherapy treatment could increase the risk of all-grade myocardial disease compared with chemotherapy. However, in most cases, there was no significant increase of risks of cardiovascular toxicity in PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor plus chemotherapy compared with chemotherapy alone.
我们进行了一项系统评价和荟萃分析，以评估接受免疫检查点抑制剂（ICI）单药治疗或ICI联合化疗的实体瘤患者发生心脏不良事件的风险。
通过以下数据库选择符合条件的研究：PubMed、Embase和临床试验（https://clinicaltrials.gov.），纳入涉及接受ICI治疗的实体瘤患者的III/IV期随机对照试验（RCT）。使用Review Manager（版本5.3）、Stata（版本15.1）对数据进行分析。
在2551项研究中，25项临床试验（包括20244例患者）符合荟萃分析的条件。与PD-1抑制剂（纳武单抗）或CTLA-4抑制剂（伊匹单抗）相比，PD-1抑制剂（纳武单抗）联合CTLA-4抑制剂（伊匹单抗）治疗的5级心律失常发生率显著增加（OR 3.90，95%CI：1.08-14.06，p = 0.603）。PD-1抑制剂联合化疗的1-5级心肌病发生率显著增加（OR 5.09，95%CI：1.11-23.32，p = 1.000）。与化疗、PD-1抑制剂（纳武单抗）或CTLA-4抑制剂（伊匹单抗）相比，PD-1抑制剂（纳武单抗）联合CTLA-4抑制剂（伊匹单抗）治疗的1-5级心律失常发生率显著增加（OR 2.49，95%CI：1.30-4.78，p = 0.289）。
我们的荟萃分析表明，与单独使用PD-1/CTLA-4抑制剂相比，PD-1抑制剂联合CTLA-4抑制剂可导致5级心律失常风险更高，与化疗相比也会导致5级心律失常风险更高。与化疗相比，PD-1抑制剂联合化疗治疗可增加全级心肌病风险。然而，在大多数情况下，与单纯化疗相比，PD-1/PD-L1抑制剂单药治疗或PD-1/PD-L1抑制剂联合化疗的心血管毒性风险没有显著增加。
