Clinical efficacy and safety of apatinib plus S-1 combined with oxaliplatin (SOX) in postoperative stage III gastric cancer patients with high VEGFR-2 expression.

BACKGROUND: The S-1 combined with oxaliplatin (SOX) regimen is the standard adjuvant chemotherapy regimen for stage III gastric cancer (GC) in China, yet 5-year survival remains only 30-40%, partly due to marked tumor heterogeneity. Apatinib, a vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, has shown significant efficacy in unresectable or metastatic GC and the neoadjuvant treatment of locally advanced GC, with response positively correlated with VEGFR-2 expression. However, SOX + apatinib has not been evaluated as an adjuvant treatment regimen in postoperative stage III GC patients with high VEGFR-2 expression. Therefore, this study aimed to evaluate the efficacy and safety of SOX + apatinib in postoperative stage III GC patients with high VEGFR-2 messenger RNA (mRNA)expression. METHODS: In this retrospective single-center study, data of 112 postoperative stage III GC patients with high VEGFR-2 mRNA expression treated at The Affiliated Hospital of Guizhou Medical University between January 2015 and June 2021 were analyzed. Patients received six 21-day cycles of adjuvant SOX alone (n=55) or SOX + apatinib (n=57), according to whether oral apatinib was administered. Disease-free survival (DFS), overall survival (OS), and safety were compared between the two groups. RESULTS: High VEGFR-2 mRNA expression was detected in 30.8% of stage III GC patients. All 112 patients had complete follow-up records, and the follow-up time was 59.3±24.2 months (range, 13-115 months). The 3-year DFS of the SOX group vs. the SOX + apatinib group was 41.8% vs. 70.2%, P=0.002; the 5-year DFS was 32.1% vs. 62.5%, P=0.002; the 3-year OS was 74.5% vs. 86.0%, P=0.13; and the 5-year OS was 34.0% vs. 64.6%, P=0.002. Univariate survival analysis and Multivariate Cox analyses both identified Borrmann classification, pathologic nodal (pN) stage, and postoperative regimen as independent predictors of DFS and OS. Kaplan-Meier analysis showed significantly improved DFS and OS with SOX + apatinib compared with SOX alone (both P<0.001). Toxicities were predominantly grade I-II and did not differ significantly between groups. CONCLUSIONS: For stage III GC patients with high expression of VEGFR-2 mRNA, SOX + apatinib therapy could improve DFS and OS and had an acceptable safety. Thus, apatinib may potentially become another targeted drug in postoperative stage III GC patients. However, future large-scale randomized clinical trials are still needed for further verification.