Efficacy and safety of systemic regimens for resectable gastric and gastroesophageal junction adenocarcinoma: a network meta-analysis of randomized controlled trials

Abstract

Perioperative systemic therapy is the standard of care for resectable locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. The emergence of multiple chemoimmunotherapy regimens warrants updated comparative evaluation. Methods A systematic review identified randomized controlled trials evaluating systemic therapy strategies for resectable locally advanced G/GEJ adenocarcinoma. Chemoradiotherapy-based approaches were not included. Overall survival (OS), disease-free survival (DFS), grade 3–4 adverse events, treatment-related discontinuation, and treatment-related deaths were analyzed. A Bayesian random-effects network meta-analysis was conducted, with treatment rankings based on surface under the cumulative ranking curve (SUCRA). Results Across 30 trials (11,547 patients), sixteen strategies were compared. Perioperative taxane-based triplet chemotherapy (P-Trp-Tax) plus an immune checkpoint inhibitor (ICI) ranked highest for OS (SUCRA = 0.952) and DFS (SUCRA = 0.959). P-Trp-Tax + ICI showed a numerically favorable trend compared with P-Trp-Tax for OS (HR 0.79; 95% CrI, 0.59–1.05), although the estimate was imprecise. A more consistent benefit was observed for DFS (HR 0.72; 95% CrI, 0.56–0.93). Comparisons versus P-Dbl + ICI were imprecise (OS HR 0.76; 95% CrI, 0.45–1.26; DFS HR 0.74; 95% CrI, 0.46–1.19). Toxicity profiles were consistent with known patterns, without increased high-grade adverse events with ICIs, with estimates limited by heterogeneity and sparse data. Conclusions P-Trp-Tax + ICI had the highest probability of being among the most effective strategies in this analysis. These findings suggest a potential benefit of treatment intensification, but should be interpreted with caution given reliance on indirect comparisons, limited direct evidence for key regimens, and wide credible intervals for several estimates.