Objective  To determine the relationship between the presence of liver metastasis, neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), and the prognosis of patients with advanced gastric cancer treated with first-line immune checkpoint inhibitors (ICIs) and chemotherapy. It also evaluated the effectiveness of ICIs as first-line therapy for patients on second-line chemotherapy.

  Methods  The clinical data of patients with gastric cancer admitted to Chinese PLA General Hospital from January 2018 to April 2022 were retrieved, and the survival data were obtained through follow-up. The Kaplan–Meier method was used to conduct the survival analysis, and a Log-rank test was performed to compare the effect of the different NLR, BMI, and liver metastasis statuses on the prognosis of patients with gastric cancer treated with first-line programmed cell death receptor-1 (PD-1)/programmed cell death-ligand1 (PD-L1) inhibitors and chemotherapy. The effect of administering first-line PD-1/PD-L1 inhibitors to patients on second-line chemotherapy was also evaluated. A Cox regression model was used to determine the prognostic factors affecting patient survival.

  Results  A total of 268 patients with advanced gastric cancer were enrolled. In the first-line PD-1/PD-L1 inhibitors combined with chemotherapy group, the overall objective response rate (ORR) and disease control rate (DCR) were 46.5% and 87.7%, respectively, while the median progression-free survival 1 (mPFS1) was 6.9 months (95%CI: 6.0–7.8). In the subgroup analysis, there was a statistical difference in median PFS1 between the NLR<3 and NLR≥3 groups (7.4 vs. 6.7 months, P=0.044). On multivariate analysis, patients with a baseline NLR<3 achieved a longer PFS after therapy with PD-1/PD-L1 inhibitors and chemotherapy than those with NLR ≥3(HR=0.57, 95%CI: 0.36–0.90; P=0.015). Meanwhile, the BMI and liver metastasis status were not significantly associated with prognosis (P>0.05). Patients who received chemotherapy alone after a failed treatment with first-line PD-1/PD-L1 inhibitors and chemotherapy had a better ORR (34.6% vs. 14.6%, P=0.025) and mPFS2 (4.4 vs. 2.9 months, HR=0.54, 95%CI:0.35–0.82; P=0.004) than those who received chemotherapy only as first-line and second-line treatments. However, there were no significant differences in DCR and median overall survival (mOS) between the two groups (P>0.05).

  Conclusions  Among advanced patients with gastric cancer who received first-line PD-1/PD-L1 inhibitors and chemotherapy, those with a baseline NLR<3 were more likely to benefit from immunotherapy. Meanwhile, liver metastasis status and BMI were not significantly associated with prognosis. Additionally, first-line treatment containing ICIs improved the efficacy of second-line chemotherapy in patients with gastric cancer, resulting in longer PFS.