Efficacy and safety of sintilimab-based neoadjuvant regimens in patients with resectable gastric or gastroesophageal junction adenocarcinoma: a single-arm systematic review and meta-analysis.

Abstract

Background: Neoadjuvant immunotherapy has emerged as a research focus in the management of resectable gastric and gastroesophageal junction (G/GEJ) cancer. Sintilimab, a fully human anti-programmed death receptor-1 (PD-1) monoclonal antibody with high PD-1 affinity, demonstrates favorable antitumor activity, safety, accessibility, and cost-effectiveness, highlighting its potential in neoadjuvant settings. This single-arm meta-analysis aimed to provide pooled estimates of efficacy and safety by aggregating the rates of tumor response, R0 resection, survival, and toxicity of neoadjuvant sintilimab-based regimens in resectable G/GEJ adenocarcinoma.

Methods: Original articles describing the safety and efficacy of sintilimab-based regimens for the neoadjuvant treatment of G/GEJ adenocarcinoma, published up to August 19, 2025, were retrieved from the Embase, PubMed/MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. STATA 16.0 was employed for data analysis.

Results: A total of 693 patients from 13 studies were included. Neoadjuvant sintilimab plus chemotherapy achieved pooled pathologic complete response (pCR) and major pathologic response (MPR) rates of 24% and 50%, respectively. Subgroup analyses showed higher pCR and MPR in prospective vs. retrospective studies. Patients with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥5 showed significantly better pCR (41% vs. 18%, P=0.02) and MPR (69% vs. 36%, P=0.002) rates than those with CPS <5. Microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) status was correlated with higher pCR (51% vs. 20%, P=0.01). Secondary outcomes included objective response rate (ORR) (75%), disease control rate (DCR) (99%), and R0 resection rate (99%). One-year disease-free survival (DFS) and overall survival (OS) were 90% and 98%; 2-year event-free survival (EFS) and OS were 67% and 83%. Common treatment-related adverse events (TRAEs) included nausea, alopecia, and hematological toxicities. Among grade ≥3 TRAEs, only lymphopenia had an incidence exceeding 10% (18%).

Conclusions: The pooled results indicate that the sintilimab-based neoadjuvant regimen offers promising efficacy and tolerability in G/GEJ adenocarcinoma. Subgroup analyses suggest higher pathological response in patients with PD-L1 CPS≥5 or MSI-H/dMMR. However, these exploratory findings require randomized controlled trials (RCTs) validation.