Efficacy and safety of immunotherapy-based neoadjuvant regimens in locally advanced gastric cancer: a meta-analysis based on high-quality clinical trials

Background: 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. Methods: 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). Results: 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. Conclusions: Immunotherapy-based neoadjuvant regimens exhibit an enhanced potential for promoting tumor regression; however, caution is warranted due to the elevated risk of severe TRAEs.