Immunotherapy: A novel approach to gastric cancer

Immune checkpoint inhibitors (ICIs) have shown promise for treating advanced gastric and esophageal adenocarcinoma, but their comparative efficacy and safety remain unclear. This study aimed to compare different ICI regimens, with or without chemotherapy, for unresectable gastric/gastroesophageal junction (GEJ) adenocarcinoma. A systematic review and Bayesian network meta-analysis was conducted on randomized clinical trials comparing ICIs or combination therapy with chemotherapy. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events. Nine trials (7922 patients) with 19 treatment regimens were included. For OS, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg showed the greatest benefit. For PFS and DCR, cadonilimab plus chemotherapy ranked highest. Pembrolizumab monotherapy had the highest ORR. PD-L1 inhibitor plus chemotherapy combinations generally showed superior efficacy compared to monotherapies or dual ICI regimens. Cadonilimab plus chemotherapy had the lowest incidence of grade ≥3 adverse events, while nivolumab-based regimens had the highest. This network meta-analysis suggests PD-L1 inhibitors combined with chemotherapy may offer the best balance of efficacy and safety for advanced gastric/GEJ cancer. However, significant heterogeneity between studies limits the reliability of indirect comparisons for some outcomes. Further research is needed to determine optimal ICI combinations and dosing. These findings can inform clinical decision-making and future trial design for immunotherapy in gastric cancer.