Abstract:Objective To analyze the clinical efficacy and the occurrence of adverse events of the oxaliplatin and capecitabine (XELOX) combined with sintilimab as a first-line treatment in patients with human epidermal growth factor receptor2 (HER2)-negative advanced gastric cancer(GC). Methods Eighty patients with HER2-negative GC admitted to the Affiliated Hospital of Xuzhou Medical University between February 2021 and December 2022 were prospectively selected. Patients were randomly assigned to the observation group and the control group, with 40 cases in each group. The control group was treated with XELOX regimen alone, and the observation group was treated with XELOX plus sintilimab. The clinical efficacy, progression-free survival (PFS), and incidence of adverse events were compared between the two groups. Results After three treatment cycles, the objective response rate (ORR) and disease control rate (DCR) in the observation group were higher than those in the control group (62.50%vs 40.00%,χ2 =4.053,P <0.05; 95.00%vs 72.50%,χ2=7.440,P <0.01）. The median PFS (mPFS) was 232.5 days in the observation group, compared to 154 days in the control group, showing a statistically significant improvement (P<0.05). Among programmed cell death ligand-1 (PD-L1) high-expression patients, the efficacy in the observation group was significantly superior to that in patients with PD-L1 low-expression (P <0.05). Additionally, the efficacy of PD-L1 low-expression patients in the observation group was higher than that of PD-L1 low-expression patients in the control group (Z =2.347,P <0.05). The incidence of treatment-related adverse events was not significantly different between the two groups (P >0.05). Conclusion The combination of XELOX and sintilimab demonstrates superior clinical efficacy and manageable safety in patients with HER2-negative advanced GC compared to XELOX alone. The regimen is particularly effective in improving the prognosis of patients with high PD-L1 expression.