免疫检查点抑制剂联合治疗实体瘤的疗效和安全性的Meta分析

目的:旨在评价免疫检查点抑制剂（immune checkpoint inhibitor，ICI）联合治疗在实体瘤患者中的安全性和有效性，为临床实践提供参考依据。方法:计算机检索 PubMed，EMBASE，Cochrane Library数据库和ClinicalTrials.gov网站符合条件的随机对照试验（randomized controlled trials，RCTs）。根据PICOS（患者类型，干预，对照，结果和研究设计）原则确定纳入标准。结果:包含6 616名患者的17项随机对照试验纳入此项Meta分析。结果显示，ICI联合治疗可显著改善实体瘤患者的总体反应率（overall response rate，ORR）［RR=1.56（95％CI 1.24，1.96），P=0.000 1］，延长无进展生存期（progression free survival，PFS）［HR=0.69（95％CI 0.59，0.81），P<0.000 01］和总生存期（overall survival，OS）［HR=0.76（95％CI 0.67，0.87），P<0.000 1］。亚组分析结果表明，接受ICI联合治疗的黑色素瘤患者的OS［HR=0.64（95％CI 0.58，0.72），P<0.000 01］显著延长，但小细胞肺癌（small cell lung cancer，SCLC）［HR=0.94（95％CI 0.82，1.08），P=0.40］和非小细胞肺癌（non-small cell lung cancer，NSCLC）［HR=0.92（95％CI 0.79，1.07），P=0.26］患者OS无显著改善。此外，ICI联合治疗可增加疲劳、皮疹、腹泻和转氨酶升高等不良反应发生风险。结论:本研究结果表明，ICI联合治疗在未来的临床实践和研究设计中极具前景。ICI联合治疗在恶性黑色素瘤患者中有临床应用价值。然而，目前的研究结果暂不支持ICI联合治疗在NSCLC和SCLC患者中大规模临床应用。

The efficacy and safety of solid tumors in combination therapy with immune checkpoint inhibitor:A systematic review

Objective:To analyse the efficacy and safety of solid tumors in combination therapy with immune checkpoint inhibitor.Methods:PubMed,EMBASE,Cochrane Library and ClinicalTrials.gov website were searched for eligible randomized controlled trials(RCTs).The selection criteria were defined according to the PICOS(population,intervention,comparison,outcome and study design)framework.Results:17 RCTs with 6616 patients were included in this Meta-analysis.The combination therapy of ICI was significantly associated with improvement of overall response rate(ORR)[RR=1.56(95%CI 1.24,1.96),P=0.0001],progression free survival(PFS)[HR=0.69(95%CI 0.59,0.81),P<0.00001]and overall survival(OS)[HR=0.76(95%CI 0.67,0.87),P<0.0001]in solid tumor.In subgroup analyses,combination ICI therapy obviously prolonged OS in melanoma patients[HR=0.64(95%CI 0.58,0.72),P<0.00001],but not in SCLC[HR=0.94(95%CI 0.82,1.08),P=0.40]and NSCLC[HR=0.92(95%CI 0.79,1.07),P=0.26]patients.As for toxicity,there was an increased risk of fatigue,rash,diarrhea and increased transaminases with combination ICI therapy.Conclusion:Our Meta-analysis indicated that combination ICI therapy is promising in future clinical practice and study designs.Combination ICI therapy has the value of clinical application in melanoma patients.However,the current data didn't support the large-scale clinical application of combination ICI therapy in NSCLC and SCLC patients.