PD-1/PD-L1抑制剂对比常规疗法治疗癌症的有效性和安全性的Meta分析

目的:系统性评价程序性死亡因子1/程序性死亡因子1配体(PD-1/PD-L1)抑制剂对比常规疗法治疗癌症的有效性和安全性。方法:计算机全面检索PubMed、MEDLINE、EMBASE数据库，收集PD-1/PD-L1抑制剂治疗癌症的文献研究，检索时间为2000年1月1日至2019年6月30日。两位研究人员独立收集和整理资料，评价纳入文献研究的偏倚风险，应用Review Manager 5.3软件对纳入研究进行数据整理。结果:最终纳入11项随机对照试验，共6 295例研究对象，其中PD-1/PD-L1抑制剂试验组3 220例，常规疗法药物对照组3 075例。Meta分析结果显示，PD-1/PD-L1抑制剂试验组的客观反应率（ORR）［RR=1.87，95%CI（1.33，2.64），P＜0.001］、完全缓解率（CR）［RR=2.45，95%CI（1.27，4.73），P＜0.001］和部分缓解率（PR）［RR=1.81，95%CI（1.28，2.54），P＜0.001］优于常规疗法对照组，结果均有统计学差异；在疾病控制率（DCR）［RR=1.03，95%CI（0.89，1.20），P=0.65］和疾病进展率（PD）［RR=1.16，95%CI（0.95，1.40），P=0.14］方面，两组比较无统计学差异；而在疾病稳定率（SD）［RR=0.72，95%CI（0.63，0.82），P＜0.001］方面显示常规疗法对照组优于PD-1/PD-L1抑制剂试验组。药物安全性方面，不良反应发生率（AEs）［RR=0.96，95%CI（0.88，1.04），P=0.28］两组无统计学差异，但在3-5级不良反应发生率［RR=0.44，95%CI（0.28，0.68），P＜0.001］方面，PD-1/PD-L1抑制剂试验组明显低于常规疗法对照组。结论:PD-1/PD-L1抑制剂与常规疗法药物相比，可明显提高癌症患者临床治疗的ORR、CR和PR，且出现3-5级不良反应发生率更低，从而证实PD-1/PD-L1抑制剂的有效性和安全性优于常规疗法。

Efficacy and safety of PD-1/PD-L1 inhibitors versus standard therapy in the treatment of cancer:A Meta-analysis

Objective:To systematically evaluate the efficacy and safety of programmed death factor 1/programmed death factor 1 ligand PD-1/PD-L1 inhibitors compared with conventional therapy in the treatment of cancer.Methods:Published clinical trials in PubMed,MEDLINE and EMBASE database on PD-1/PD-L1 inhibitors in the treatment of cancers were analyzed from January 1,2000 to June 30,2019.Two researchers collected related studies.Risk of bias of included studies was evaluated and Review Manager 5.3 software analyzed data.Results:A total of 6295 cancer patients were enrolled in 11 randomized controlled clinical trials.From the results of Meta analysis,we found that 3220 and 3075 patients were treated with PD-1/PD-L1 inhibitors and standard therapy group,respectively.The objective response rate(ORR)RR=1.87,95%CI(1.33,2.64),P<0.001],complete response(CR)RR=2.45,95%CI(1.27,4.73),P<0.001]and partial response(PR)RR=1.81,95%CI(1.28,2.54),P<0.001]of patients treated with PD-1/PD-L1 inhibitors were superior compared with standard therapy group.Nevertheless,there were no significant differences between two groups in disease control rate(DCR)RR=1.03,95%CI(0.89,1.20),P=0.65]and progressive disease(PD)RR=1.16,95%CI(0.95,1.40),P=0.14].And the stable disease(SD)RR=0.72,95%CI(0.63,0.82),P<0.001]of standard therapy group was better than that in the PD-1/PD-L1 inhibitors group.In terms of drug safety,there was no significant difference in the incidence of adverse effects(AEs)RR=0.96,95%CI(0.88,1.04),P=0.28]between two groups.But the incidence of 3-5 grade adverse reactionsRR=0.44,95%CI(0.28,0.68),P<0.001]of PD-1/PD-L1 inhibitors group was lower than that standard therapy group.Conclusion:Compared with standard therapeutic drugs,PD-1/PD-L1 inhibitors could significantly improve the objective response rate(ORR),complete response(CR)and partial response(PR).The incidence of 3-5 grade adverse reactions of PD-1/PD-L1 inhibitors group was lower than standard therapy group,so as to prove that the efficacy and safety of PD-1/PD-L1 inhibitors are better than standard therapeutic drugs.