Combination of Immune Checkpoint Inhibitors With Vascular Endothelial Growth Factor-Targeted Agents in Advanced Gastric and Gastroesophageal Adenocarcinoma: A Systematic Review and Meta-analysis.

Gastric and gastroesophageal junction (G/GEJ) adenocarcinomas remain a major global health burden. Combining antiangiogenic agents with immune checkpoint inhibitors (ICIs) may enhance antitumor activity and improve outcomes. This systematic review and meta-analysis evaluated the efficacy and safety of ICIs plus VEGF-targeted agents in advanced G/GEJ adenocarcinoma. A comprehensive search across multiple databases was conducted till March 2026. Original studies evaluating ICIs plus VEGF-targeted agents in adults with advanced, unresectable, or metastatic G/GEJ adenocarcinoma and reporting overall response rate (ORR) were included. Proportions with 95% CIs were pooled. Twenty-six studies involving 1354 patients were included. Camrelizumab, pembrolizumab, and nivolumab were the most commonly used ICIs, while apatinib was the most frequently used VEGF-targeted agent. The pooled ORR was 33% (95% CI, 24%-44%) and the disease control rate (DCR) was 79% (95% CI, 72%-85%). Stable disease and progressive disease rates were 42% (95% CI, 36%-47%) and 17% (95% CI, 12%-24%), respectively. Pooled progression-free survival rates were 39%, 17%, and 9% at 6, 12, and 18 months, respectively. Corresponding overall survival rates were 72%, 44%, and 24%. Subgroup analysis showed that adding chemotherapy to ICIs plus VEGF-targeted agents improved ORR (56%), DCR (90%), and survival outcomes. The most commonly reported adverse events were neutropenia (38%), and thrombocytopenia (33%). ICIs plus VEGF-targeted agents showed promising activity, particularly when combined with chemotherapy. However, substantial interstudy heterogeneity limits definitive conclusions, highlighting the need for larger, standardized trials to optimize treatment strategies and identify patients most likely to benefit.