Efficacy and safety of immune checkpoint inhibitors in gastric cancer: a network meta-analysis of well-designed randomized controlled trials

BACKGROUND: Immune checkpoint inhibitors (ICIs) that inhibit the programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) interactions have shown promising prospects as treatment options for advanced gastric cancer (AGC). This manuscript analyzed well designed clinical trials to evaluate the efficacy and safety of immunotherapy in AGC. METHODS: PubMed, Embase, the Cochrane Library, and Medline were searched for randomized controlled trials (RCTs) of AGC treatments that were published before April 2020. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAEs) were evaluated to determine the efficacy and safety of ICIs. Network meta-analysis was performed using a random-effects model under the Bayesian framework. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve. RESULTS: Our analysis included five studies having seven immunotherapy regimens and 1,730 patients. The network meta-analysis showed that nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks (88.369%) was the regimen most likely to improve PFS. Nivolumab 3 mg/kg every 3 weeks (84.563%) and nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks (84.556%) were similarly best for OS outcome with excellent tolerance. The regimen of avelumab 10 mg/kg every 2 weeks (91.167%) had the lowest TRAEs. All immunotherapies had similar response rates. CONCLUSIONS: We recommend nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks as the preferred regimen due to their high efficacies.