What question did this study set out to answer?

The aim is to evaluate the efficacy and safety of systemic therapy regimens for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma.

May 18, 2026Open Access

Efficacy and Safety of Systemic Regimens for Resectable Gastric and Gastroesophageal Junction Adenocarcinoma: A Network Meta-analysis of Randomized Controlled Trials

Key Points

The aim is to evaluate the efficacy and safety of systemic therapy regimens for resectable locally advanced gastric and gastroesophageal junction adenocarcinoma.
Conducted a systematic review of randomized controlled trials for systemic therapy strategies.
Excluded chemoradiotherapy-based approaches and analyzed overall survival, disease-free survival, and adverse events.
Performed a Bayesian random-effects network meta-analysis with treatment rankings based on SUCRA.
P-Trp-Tax plus ICI ranked highest for overall survival (SUCRA = 0.952) and disease-free survival (SUCRA = 0.959).
P-Trp-Tax + ICI showed a favorable trend for overall survival (HR 0.79; 95% CrI, 0.59-1.05) and a consistent benefit for disease-free survival (HR 0.72; 95% CrI, 0.56-0.93).
Toxicity profiles were consistent with known patterns, without increased high-grade adverse events from ICIs.

Abstract

BACKGROUND: 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.

Efficacy and Safety of Systemic Regimens for Resectable Gastric and Gastroesophageal Junction Adenocarcinoma: A Network Meta-analysis of Randomized Controlled Trials

Key Points

Abstract

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