Efficacy and safety of immunotherapy combinations in advanced esophageal and gastric cancers: A systematic review and bayesian network meta-Analysis

Background: Immune checkpoint inhibitors (ICIs) have yielded a revolution in the treatment of esophageal, gastroesophageal junction, and gastric cancers cancers. We made a Bayesian network meta-analysis to systematically compare the efficacy and safety of various immunotherapies, chemotherapy, and supportive treatment, and to further identify the best benefitting subgroup. Methods: We systematically searched Pubmed/MEDLINE, Embase, Cochrane Library and the conference abstracts of oncology conferences up to July 25, 2022. The Bayesian network meta-analysis was performed with a random-effect model using R, package gemtc and package JAGS. The primary outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and grade 3-5 adverse events (AEs). Results: Totally 11719 patients from 20 RCTs (19/20 were phase 3) were included, which were divided into 12 treatment regimens. Immune monotherapies yield superior OS benefit (HR = 0.89, 95% CI: 0.83–0.95), but inferior PFS (HR = 0.75, 95% CI: 0.7–0.8) compared with chemotherapy. Except for Nivo_5FCisp (HR = 0.8, 95% CI: 0.49–1.32), Nivo_S1Oxal (HR = 0.9, 95% CI: 0.75–1.08), Tori_PacCisp (HR = 0.91, 95% CI: 0.77–1.07), the other ICIs combined chemotherapy (IO) had a significant OS benefit compared with chemotherapy. Except for Nivo_5FCisp, the other IO regimens had significant PFS benefits than chemotherapy. There were no significantly statistical differences of ORR and grade 3-5 AEs. Sin_PacCisp and Cam_PacCisp achieved an effective balance between efficacy and safety. The former regimen ranked second for OS (48.3%), PFS (29.5%), ORR (18.4%), and sixth for grade 3-5 AEs (7.2%), the later one ranked third for OS and PFS, fifth for ORR and ninth for grade 3-5 AEs. Esophagogastric cancers with higher PD-L1 expression levels might benefit more from immunotherapies. Conclusion: We found immunotherapis were more likely to provide OS and PFS superiority compared with chemotherapy, with no significantly statistical differences of ORR and grade 3-5 AEs. Sin_PacCisp and Cam_PacCisp achieved an effective balance between efficacy and safety. Esophagogastric cancers with higher PD-L1 expression levels might benefit more from immunotherapies.