SYSTEMATIC REVIEW article
Front. Med.
Sec. Gastroenterology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1625259
This article is part of the Research TopicResearch on Biomarkers for Immunotherapy in Gastrointestinal Tumors: Basic Exploration and Clinical ApplicationView all 5 articles
Neoadjuvant PD-1/PD-L1 Inhibitors Combined with Chemotherapy in Gastric Cancer and Gastroesophageal Junction Adenocarcinoma: A Systematic Review and Meta-Analysis of Single-Arm Studies
Provisionally accepted
- North Sichuan Medical College, Nanchong, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background:Neoadjuvant chemotherapy, particularly neoadjuvant immunotherapy, has achieved significant progress in treating gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma. While PD-1/PD-L1 inhibitors have improved survival outcomes in some patients, the efficacy of combining neoadjuvant chemotherapy with PD-1/PD-L1 inhibitors remains insufficiently validated.Objective:This study aims to evaluate the efficacy and safety of neoadjuvant chemotherapy combined with PD-1/PD-L1 inhibitors in GC/GEJ adenocarcinoma and enhance statistical power through meta-analysis.Methods:We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library up to October 5, 2024, for original clinical studies on neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy for GC/GEJ adenocarcinoma. Eligible studies were evaluated using the Methodological Index for Non-Randomized Studies(MINORS) Criteria. Meta-analysis was performed using R 4.4.2 software.Results:A total of 12 studies involving 428 patients were included. The primary efficacy outcomes were pathological complete response (pCR) and major pathological response (MPR), while secondary outcomes included disease control rate (DCR) and the rate of lymph node downstaging to ypN0. The effect size (ES) for pCR was 20.94% [95% CI: 0.1698; 0.2518], and for MPR, the ES was 55.86% [95% CI: 0.4891; 0.6271]. Safety was evaluated using the incidence of grade ≥3 treatment-related adverse events (trAEs), immune-related adverse events (irAEs), postoperative complications, and R0 resection rate. The meta-analysis revealed that 406 patients underwent surgical intervention, with 88 achieving pCR. The pooled effect size for R0 resection rate was 95.2% [95% CI: 0.896; 0.989]. The ES values for grade ≥3 adverse events, immune-related adverse events, and postoperative complications were 0.54 [95% CI: 0.30; 0.77], 0.17 [95% CI: 0.07; 0.31], and 0.28 [95% CI: 0.15; 0.44], respectively.
Keywords: combination therapy, efficacy, Meta-analysis, neoadjuvant immunotherapy, gastric cancer/gastroesophageal junction tumors, Safety, PD-1/PD-L1 inhibitors
Received: 08 May 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Leng, Liu, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jin Chen, North Sichuan Medical College, Nanchong, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.