Liang Chen, Yu Zhiyuan, Li Rui, Xu Tao, Hou Siyu, Zheng Junfu, Chen Weina, Jia Chunzeng, Gao Yan, Gao Pengji, Li Lei
Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University.
Int J Surg. 2025 Jun 20. doi: 10.1097/JS9.0000000000002815.
The integration of chemotherapy, targeted therapy, and immunotherapy has emerged as the latest research focus for locally advanced gastric cancer (LAGC). This study aims to evaluate the efficacy and safety of various immunotherapy-based neoadjuvant regimens for LAGC.
PubMed, EmBase, and Cochrane Library databases were systematically searched based on the predefined inclusion criteria. Subsequently, the Stata software (version 17) was employed to separately integrate the outcome indicators of the single- and dual-arm studies, thereby systematically assessing the antitumor effects of three distinct immunotherapy-based regimens: neoadjuvant immunotherapy plus chemotherapy (NICT), neoadjuvant chemotherapy plus targeted therapy (NCTT), and NICT plus targeted therapy (NICTT).
16 high-quality Phase II prospective single-arm clinical studies and 7 dual-arm clinical studies were selected. The pooled results from the single-arm studies indicated that immune-based neoadjuvant therapy could increase the rates of pathological complete response (pCR), severe treatment-related adverse events (TRAEs), 1- and 3-year disease-free survival (DFS), as well as 1- and 3-year overall survival (OS) to 20%, 30%, 91%, 74%, 94%, and 81%, respectively. Pairwise meta-analysis indicated that both the NICT and NICTT groups achieved higher rates of pCR, major pathological response (MPR), and complete resection (R0 resection) compared to the neoadjuvant chemotherapy (NCT) group, with the NICTT group exhibiting more pronounced effects. The NICTT group exhibited a significantly higher risk of experiencing severe TRAEs compared to the NCT group. ICIs + XELOX appeared to be a more appropriate NICT regimen, as it effectively enhanced the tumor response rate while inducing less severe TRAEs. Tumors exhibiting positive expression of PD-L1 or microsatellite instable (MSI) demonstrated a higher level of responsiveness to the NICT regimen.
Immunotherapy-based neoadjuvant regimens exhibit an enhanced potential for promoting tumor regression; however, caution is warranted due to the elevated risk of severe TRAEs.
化疗、靶向治疗和免疫治疗的联合应用已成为局部晚期胃癌（LAGC）的最新研究热点。本研究旨在评估各种基于免疫治疗的新辅助方案对LAGC的疗效和安全性。
根据预先设定的纳入标准，系统检索PubMed、EmBase和Cochrane图书馆数据库。随后，使用Stata软件（版本17）分别整合单臂和双臂研究的结局指标，从而系统评估三种不同的基于免疫治疗的方案：新辅助免疫治疗联合化疗（NICT）、新辅助化疗联合靶向治疗（NCTT）以及NICT联合靶向治疗（NICTT）的抗肿瘤效果。
选取了16项高质量的II期前瞻性单臂临床研究和7项双臂临床研究。单臂研究的汇总结果表明，基于免疫的新辅助治疗可将病理完全缓解（pCR）率、严重治疗相关不良事件（TRAEs）、1年和3年无病生存率（DFS）以及1年和3年总生存率（OS）分别提高至20%、30%、91%、74%、94%和81%。成对荟萃分析表明，与新辅助化疗（NCT）组相比，NICT组和NICTT组均实现了更高的pCR率、主要病理缓解（MPR）率和完全切除（R0切除）率，其中NICTT组的效果更为显著。与NCT组相比，NICTT组发生严重TRAEs的风险显著更高。ICIs + XELOX似乎是一种更合适的NICT方案，因为它能有效提高肿瘤反应率，同时诱导的TRAEs较轻。PD-L1呈阳性表达或微卫星不稳定（MSI）的肿瘤对NICT方案表现出更高的反应水平。
基于免疫治疗的新辅助方案具有增强的促进肿瘤消退的潜力；然而，由于严重TRAEs风险升高，需谨慎使用。
