PD-1/PD-L1单抗治疗晚期非小细胞肺癌引起免疫治疗相关性肺炎的网状Meta分析

目的:采用网状Meta分析(network meta-analysis，NMA)，比较程序性细胞死亡蛋白-1及其配体(PD-1/PD-L1)单克隆抗体的不同治疗方案在晚期非小细胞肺癌(NSCLC)中导致免疫治疗相关性肺炎(IRP)的风险。方法:从PubMed、Embase和Cochrane Library数据库中检索PD-1/PD-L1单抗治疗晚期NSCLC的Ⅱ/Ⅲ期随机对照试验(RCT)，检索时限为建库起至2021年6月1日。采用STATA 16.0和R软件4.1.0进行NMA。结果:共纳入30篇RCTs，包含18 425名患者。1~5级IRP的NMA结果显示，与化疗相比，PD-1单抗以及PD-L1单抗治疗均导致IRP的风险增高(P<0.05);PD-1单抗单药比PD-L1单抗单药及PD-L1单抗联合化疗发生IRP的风险增加(P<0.05);PD-1单抗+CTLA-4抑制剂发生IRP的风险高于PD-L1单抗、PD-1/PD-L1单抗+化疗(P<0.05);在3~5级IRP中，PD-1单抗、PD-1/PD-L1单抗+CTLA-4抑制剂发生IRP的风险高于PD-L1单抗+化疗(P<0.05);PD-1单抗+化疗发生重度IRP的风险低于PD-1单抗+CTLA-4抑制剂(P<0.05)。累积排序曲线下面积排序结果显示:发生1~5级和3~5级IRP可能性最高的均为PD-1单抗+CTLA-4抑制剂。结论:在晚期NSCLC的治疗中，PD-1/PD-L1单抗发生IRP的风险均高于化疗，PD-1单抗+CTLA-4抑制剂发生IRP的可能性最高，PD-1单抗发生IRP的风险高于PD-L1单抗。

PD-1/PD-L1 inhibitors induced immune-related pneumonitis in patients with advanced non-small cell lung cancer:A network Meta-analysis

OBJECTIVE To compare the risk of immune-related pneumonitis(IRP) among different treatments of programmed cell death protein-1/programmed cell death ligand-1(PD-1/PD-L1) inhibitors for advanced non-small cell lung cancer(NSCLC) through network Meta-analysis(NMA).METHODS PubMed,Embase and the Cochrane Library were searched for all phase Ⅱ/Ⅲ randomized clinical trial(RCT) with PD-1/PD-L1 inhibitors for advanced NSCLC,before June 1,2021.STATA 16.0 and R software(version 4.1.0) were used for NMA.RESULTS 30 RCTs involving a total of 18 427 patients were included.For grade 1-5 IRP,the results of NMA showed that compared with chemotherapy,both PD-1 and PD-L1 inhibitors were associated with higher risk of all-grade IRP(P<0.05).Compared with PD-L1 inhibitor monotherapy or PD-L1 combined with chemotherapy,PD-1 inhibitor monotherapy was associated with higher risk of all-grade IRP(P<0.05).Compared with PD-1 inhibitor+CTLA-4 inhibitor,PD-L1 inhibitor monotherapy,and PD-1/PD-L1 inhibitor+chemotherapy were related to lower risk of all-grade IRP(P<0.05).For grade 3-5 IRP,the results of NMA showed that compared with PD-L1 inhibitor+chemotherapy,PD-1 inhibitor monotherapy,and PD-1/PD-L1 inhibitor+CTLA-4 inhibitor were associated with higher risk of high-grade IRP(P<0.05).Compared with PD-1 inhibitor+CTLA-4 inhibitor,PD-1 inhibitor+chemotherapy was associated with lower risk of high-grade IRP(P<0.05).The sorting results of NMA showed that PD-1 inhibitor+CTLA-4 inhibitor was associated with the highest risk of all and high grade IRP according to surface under cumulative ranking curve.CONCLUSION In the treatment of advanced NSCLC,PD-1/PD-L1 inhibitor were associated with higher risk of all-grade IRP than chemotherapy,PD-1 inhibitor+CTLA-4 inhibitor has the highest risk of both grade 1-5 and grade 3-5 IRP,PD-1 inhibitor lead to higher risk of IRP than PD-L1 inhibitor.