Efficacy and safety of neoadjuvant apatinib plus PD ‐1 inhibitor with SOX for locally advanced gastric cancer: A multicenter, retrospective cohort study

Although neoadjuvant PD-1 inhibitors combined with chemotherapy are promising for locally advanced gastric cancer (LAGC), pathological complete response (pCR) rates remain suboptimal. This multicenter retrospective study (January 2020-September 2024) evaluated the synergistic potential of adding apatinib to the neoadjuvant framework of PD-1 inhibitors plus SOX chemotherapy (PA-SOX) versus the doublet regimen (P-SOX). From a multi-institutional cohort of 449 patients, 1:1 propensity score matching (PSM) was employed to yield 102 well-balanced pairs. The PA-SOX regimen demonstrated a significantly superior primary endpoint, achieving a pCR rate of 17.6% compared to 6.9% in the P-SOX group (p = 0.031; FDR-adjusted p = 0.036). This pathological advantage was further reflected in significantly higher major pathological response (MPR; 38.2% vs. 15.7%, p < 0.001) and objective response rates (ORR; 62.7% vs. 33.3%, p < 0.001). Survival analysis demonstrated improved 2-year overall survival (82.4% vs. 69.9%; HR = 0.32, 95% CI: 0.15-0.66; p = 0.001) and disease-free survival (71.1% vs. 41.7%; HR = 0.35, 95% CI: 0.22-0.57; p < 0.001). Safety profiles were manageable, with no significant increase in Grade 3-4 adverse events (p = 0.503) or postoperative morbidity (p = 0.718), supported by a standardized preoperative washout protocol. Multivariate analysis confirmed PA-SOX as an independent protective factor for survival. In conclusion, these retrospective findings suggest that adding apatinib to the neoadjuvant immunochemotherapy backbone may optimize pathological responses and enhance short-term survival for LAGC with a tolerable safety profile; however, the durability of these survival benefits warrants validation in large-scale, randomized phase III trials.