程序性细胞死亡1受体/程序性死亡配体1抑制剂的心脏毒性meta分析

Cardiotoxicity of programmed cell death 1 receptor/programmed cell death ligand 1 inhibitors:a meta-analysis

目的系统评价程序性细胞死亡1受体(PD-1)/程序性死亡配体1(PD-L1)抑制剂的心脏毒性。方法检索国内外有关数据库(截至2019年3月2日),收集PD-1/PD-L1抑制剂单药或联合其他方案治疗肿瘤的临床试验,采用国际通用的Cochrane协作网偏倚风险评估工具进行方法学质量评价,采用RevMan 5.3软件进行meta分析,比较PD-1/PD-L1抑制剂(试验组)与安慰剂或其他抗肿瘤药物(对照组)心脏毒性的发生率。结果共纳入了10项随机对照试验(RCT),9项为PD-1抑制剂单药或联合其他抗肿瘤药物的研究,1项为PD-L1抑制剂单药治疗的研究,共包括5291例患者,其中试验组3022例,对照组2269例患者。质量评价结果显示,10项RCT中4项为高偏倚风险,6项为低偏倚风险。meta分析结果表明,试验组心脏毒性发生率显著高于对照组[1.13%(34/3022)比0.22%(5/2269),相对危险度=2.38,95%置信区间:1.19~4.78,P=0.01],差异有统计学意义。结论PD-1/PD-L1抑制剂有导致心脏相关不良事件的风险,临床应用中应警惕。

Objective To systematically evaluate cardiotoxicity of programmed cell death 1 receptor(PD-1)/programmed cell death ligand 1(PD-L1)inhibitors.Methods Clinical trials of PD-1/PD-L1 inhibitor alone or in combination with other treatments for tumors were collected by searching related databases at home and abroad(up to March 2,2019).The methodological quality of studies was evaluated using the internationally accepted Cochrane collaboration′s risk of bias assessment tool.A meta-analysis was performed using RevMan 5.3 software to compare the incidences of cardiotoxicity between PD-1/PD-L1 inhibitors(trial group)and placebo or other antineoplastic agents(control group).Results A total of 10 randomized controlled trials(RCTs)were enrolled,9 of which were about PD-1 inhibitor alone or in combination with other antineoplastic agents,and 1 of which was about PD-L1 inhibitor monotherapy.There were a total of 5291 patients,including 3022 in the trial group and 2269 in the control group.Evaluation of the methodological quality for studies showed that 4 RCTs were at high risk of bias and the other 6 were at low risk of bias.The meta-analysis showed that the incidence of cardiotoxicity in the trial group was significantly higher than that in the control group,and the difference was statistically significant[1.13%(34/3022)vs.0.22%(5/2269),RR=2.38,95%CI:1.19-4.78,P=0.01].Conclusion PD-1/PD-L1 inhibitors have the risk of causing heart related adverse events,which should be paid attention to in clinical application.