Objective The aims of this study were to compare the clinical effectiveness of an immunosuppressant (sintilimab) combined with different chemotherapy regimens (two- and three-drug regimens) in the neoadjuvant treatment of advanced gastric cancer and to explore the efficacy-associated clinical features.

Methods A retrospective analysis was conducted on patients with advanced gastric cancer who received treatment at Lanzhou University Second Hospital between August 2020 and February 2024. Overall, 133 patients were included in the study and assigned into groups A (three-drug regimens) and B (two-drug regimens), according to the treatment regimen received. Recent efficacy outcomes, including the pathological complete response rate (pCR), major pathological response rate (MPR), objective response rate (ORR), and disease control rate (DCR), as well as long-term efficacy outcomes, including overall survival (OS) and disease-free survival (DFS), were compared. Subgroup analyses were performed to identify clinical features associated with treatment efficacy.

Results The recent efficacy outcomes were similar between groups A (two-drug regimen) and B (three-drug regimen), with pCRs of 18.46% and 27.94%, MPRs of 52.31% and 58.82%, ORRs of 76.92% and 76.47%, and DCRs of 87.69% and 95.59%, respectively. However, the three-drug regimen led to significantly improved OS and DFS, compared with the two-drug regimen (P<0.05). Subgroup analysis revealed that male patients and those with gastric antrum cancer, an ECOG score of 0, a T4 stage tumor, and no vascular or nerve invasion benefited more from the three-drug regimen.

Conclusions Sintilimab combined with the three-drug chemotherapy regimen demonstrated superior long-term efficacy in the neoadjuvant treatment of advanced gastric cancer, compared with the combination with the two-drug regimen. Certain clinical features may predict greater benefit from the three-drug regimen.