Efficacy And Safety Of Immune Checkpoint Inhibitors Therapy On Advanced Gastric Cancer: A Meta-analysis

Objective:To evaluate the efficacy and safety of immune checkpoint inhibitors(ICIs)in patients with advanced gastric cancer(AGC)by meta-analysis.Methods:Wanfang,CNKI,VIP,CBM,Embase,Pub Med,Cochrane Library,Web of Science and other large and medium-sized English databases were searched to find the randomized controlled trials(RCT)of ICIs in the treatment of AGC published before December2021.The outcome indicators included overall survival(OS),progression free survival(PFS),objective response rate(ORR),disease control rate(DCR)and treatment-related adverse events(TRAEs)were determined by Rev Man 5.4.1 software for meta-analysis to evaluate the efficacy and safety of ICIS in GC patients.Results:Our analysis included 9 studies having 7 original literatures and 2 conference abstracts,including 5751 AGC patients.After summarizing the data,we found that immunotherapy prolonged the OS(HR=0.86,95%CI:0.76～0.97,P=0.01)of AGC patients,but did not improve PFS(HR=0.99,95%CI:0.78～1.25,P=0.91).In the analysis of subgroup,we found the ICIs were better than placebo and ICIs combined chemotherapy were also better than chemotherapy alone in term of extending the OS and PFS of patients.In addition,immunotherapy prolonged OS and PFS as the first-line treatment,and only OS as the second-line treatment.Comparing the OS of AGC patients treated with different types of ICIs,it was found that PD-1 inhibitor significantly prolonged the OS.In patients with PD-L1 CPS≥1,≥5,≥10,immunotherapy improved the OS of patients,and the difference was statistically significant.Compared with the control group,ORR and DCR were not statistically significant.Subgroup analysis showed that ICIs combined chemotherapy increased ORR compared with chemotherapy,and the improvement of DCR was not statistically significant.In terms of safety,the overall population included was analyzed,and it was found that the difference of ≥grade 3 TRAEs was not statistically significant.Subgroup analysis showed that the incidence of ≥grade 3 TRAEs in ICIs was lower than that in chemotherapy.The incidence of serious adverse events in PD-L1 inhibitor group was lower than that in control group.Conclusion:Immunotherapy combined with chemotherapy prolongs OS,PFS and ORR in patients with AGC.When immunotherapy is used as the first-line treatment,OS and PFS benefit significantly.PD-1 inhibitor prolonged the OS of patients compared with the other two ICIs.For patients with PD-L1 positive expression,the survival benefit of immunotherapy was better than that of the control group.PD-L1 inhibitors have a lower incidence of severe TRAEs and may have better safety.