Efficacy and safety of first-line immunotherapy for advanced gastric or gastroesophageal cancer: System review network meta-analysis

e16014 Background: In advanced gastric or gastroesophageal cancer, a series of randomized controlled trials had investigated different first-line immunotherapy compared with chemotherapy. However, the optimal immunotherapy strategy is yet to be established. We compared the efficacy and safety of first line immunotherapy for patients with advanced, HER2-negative gastric or gastroesophageal junction cancer. Methods: We performed systematic review and a network meta-analysis (NMA) of immune checkpoint inhibitors (ICIs) monotherapy or combined with chemotherapy for gastric or gastroesophageal cancer with HER2 negative. We searched PubMed, Embase, Cochrane Central Register of Controlled Trails, ClinicalTrials.gov, and several international conference databases, from 1 January 2012 to 1 March 2022.Published and unpublished randomized controlled trials compared different first-line immunotherapy with chemotherapy were included. This study was registered in the Prospective Register of Systematic Reviews (CRD 42021291609) to ensure transparency. Results: We analyzed a total 5 studies including 5279 patients and involving 5 immunotherapies. In patients without programmed death-ligand 1(PD-L1) selection, ICIs combined with chemotherapy improved progression free survival (PFS) and overall survival (OS). Sintilimab plus chemotherapy provided the best OS benefit (HR=0.77, 95% CI 0.63-0.94) and the best PFS benefit (HR=0.64, 95%CI 0.53-0.77) compared with standard chemotherapy. Furthermore, pembrolizumab plus chemotherapy seemed to provide the best objective response rate (OR= 1.81, 95%CI 1.44-2.28). Pembrolizumab monotherapy was the safest first-line treatment for grade equal or more 3 AEs (OR= 0.09, 95% CI 0.06-0.14). Subgroup analysis showed that sintilimab plus chemotherapy was associated with the best OS in CPS PD-L1≥1 (HR=0.73,95%CI 0.59-0.91) and PD-L1 ≥10 (HR=0.56, 95% CI 0.41-0.77). Pembrolizumab monotherapy improved OS in PD-L1 ≥10 (HR=0.69, 95% 0.49-0.97). Conclusions: Our results indicate that Sintilimab combined chemotherapy were associated with the best PFS and OS for patients with advanced GC or GEJC with HER2 negative.