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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

In brief

Neoadjuvant sintilimab-chemo achieves 24% pathologic complete response in resectable gastric cancer

In a pooled analysis of 693 patients, adding sintilimab to chemotherapy before surgery produced a 24% complete pathological response and a 50% major response, with 99% achieving clear margins and 90% disease-free at one year. Responses were especially high in tumors with PD-L1 CPS at least 5 or MSI-H/dMMR, but the evidence comes from single-arm studies and needs confirmation in randomized trials.

Journal
Journal of gastrointestinal oncology (Q2)
Published
21 July 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Tingting Nan, Siheng Lian, Xiaohong Wu, Ruina Cai, Yumei Cai, Yonglong Su, et al.
PMID
42703297
DOI
10.21037/jgo-2026-0479

Why clinicians should know about it

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.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.