ICIs对比常规二线化疗方案用于晚期食管癌有效性与安全性的Meta分析

Efficacy and safety of immune checkpoint inhibitors versus routine second-line chemotherapy for advanced esophageal cancer:a meta-analysis

目的系统评价免疫检查点抑制剂(ICIs)对比常规二线化疗方案用于晚期食管癌的有效性和安全性,为临床用药提供循证参考。方法计算机检索PubMed、Embase、Cochrane图书馆、中国知网、万方数据、维普网,收集ICIs(试验组)对比常规二线化疗方案(对照组)用于晚期食管癌的随机对照试验(RCT),检索时限为建库起至2021年8月1日。筛选文献、提取资料后采用Cochrane系统评价员手册5.1.0推荐的偏倚风险评估工具对纳入文献进行质量评价,采用RevMan 5.4.1软件进行Meta分析和敏感性分析。结果共纳入4项研究,共计1656例患者。Meta分析结果显示,试验组患者的总生存期显著长于对照组[HR=0.79,95%CI(0.71,0.88),P<0.0001]、3级及以上不良事件发生率显著低于对照组[RR=0.42,95%CI(0.32,0.54),P<0.00001],两组患者的无进展生存期[HR=0.95,95%CI(0.75,1.21),P=0.70]、客观缓解率[RR=1.72,95%CI(0.95,3.13),P=0.07]比较,差异均无统计学意义。按患者程序性死亡配体1表达的不同进行的亚组分析结果显示,试验组中肿瘤比例分数≥1%患者的总生存期显著长于对照组[HR=0.64,95%CI(0.51,0.79),P<0.0001];两组肿瘤比例分数<1%患者的总生存期[HR=0.83,95%CI(0.67,1.02),P=0.07]比较,差异无统计学意义。敏感性分析结果显示,除客观缓解率外,其余指标所得结果均稳定。结论ICIs较常规二线化疗方案可延长晚期食管癌患者的总生存期,且安全性较好,但在无进展生存期和客观缓解率方面未显示出优势。

OBJECTIVE To systematically evaluate the efficacy and safety of immune checkpoint inhibitors(ICIs)versus routine second-line chemotherapy in the treatment of advanced esophageal cancer,and to provide evidence-based reference for clinical medication.METHODS Randomized controlled trials(RCTs)about ICIs(trial group)versus routine second-line chemotherapy(control group)in the treatment of advanced esophageal cancer were searched from PubMed,Embase,The Cochrane Library,CNKI,Wanfang and VIP databases from the inception to August 1st,2021.After screening the literature and extracting data,the risk of bias assessment tool recommended by Cochrane Systematic Evaluator Manual 5.1.0 was used to evaluate the quality of the included literature,and RevMan 5.4.1 software was used for meta-analysis and sensitivity analysis.RESULTS A total of four studies were included,involving 1656 patients.Meta-analysis results showed that the overall survival of trial group was significantly longer than control group[HR=0.79,95%CI(0.71,0.88),P<0.0001];the incidence of grade 3 or higher adverse events in trial group was significantly lower than control group[RR=0.42,95%CI(0.32,0.54),P<0.00001].But there was no significant difference in progression-free survival[HR=0.95,95%CI(0.75,1.21),P=0.70]or objective remission rate[RR=1.72,95%CI(0.95,3.13),P=0.07]between 2 groups.Results of subgroup analysis was performed according to the expression of programmed death ligand 1 showed that overall survival of patients with tumor proportion score(TPS)≥1%in trial group was significantly longer than control group[HR=0.64,95%CI(0.51,0.79),P<0.0001];there was no significant difference in overall survival of patients with TPS<1%between 2 groups[HR=0.83,95%CI(0.67,1.02),P=0.07].The results of sensitivity analysis showed that except for the objective remission rate,the conclusions of other indicators were robust.CONCLUSIONS Compared with routine second-line treatment,ICIs can prolong overall survival and has good safety,but shows no advantage in terms of progression-free survival and objective response rates.