Comparative study of the efficacy and safety of PSOX and SOX plus sintilimab regimens as first-line treatments for advanced gastric cancer.

Abstract

Advanced gastric cancer (AGC) remains associated with poor survival despite advances in multimodal treatment. Recent trials suggest that adding programmed death-1 inhibitors to chemotherapy may improve outcomes in HER2-negative AGC, but real-world evidence-particularly in surgical settings-remains limited. This retrospective study evaluated the efficacy and safety of SOX plus sintilimab compared with P-SOX in patients with AGC undergoing perioperative chemotherapy followed by standard D2 gastrectomy. A total of 242 patients were included, of whom 161 received P-SOX and 81 received SOX plus sintilimab. Short-term response, long-term survival outcomes, and treatment-related adverse events were compared between groups. Prognostic factors for progression-free survival (PFS) were further analyzed in patients treated with SOX plus sintilimab. The SOX plus sintilimab regimen achieved superior short-term efficacy, with higher objective response rates by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (70.4% vs. 47.2%) and higher tumor regression grades (91.4% vs. 72.7%) compared with P-SOX (both P < 0.001). Median overall survival was significantly longer in the SOX plus sintilimab group (32.0 vs. 29.0 months; HR = 0.617, P  = 0.006), while PFS showed a borderline improvement. Treatment-related adverse events were mostly grade 1-2, with comparable rates of severe toxicities between groups; immune-related events were infrequent. Poor perioperative treatment response, larger tumor size, poor differentiation, and advanced stage were independently associated with worse PFS. In conclusion, SOX plus sintilimab offers improved efficacy with acceptable safety compared with P-SOX, providing supportive real-world evidence for its use in AGC.