Efficacy of immune checkpoint inhibitors combined with chemotherapy for advanced gastric cancer.

OBJECTIVE: To investigate the effects and safety of immune checkpoint inhibitors (ICIs) combined with chemotherapy for advanced gastric cancer, and to evaluate the predictive value of pretreatment peripheral blood inflammatory markers and tumor markers for progression-free survival (PFS). METHODS: A retrospective analysis was performed on 89 patients with advanced gastric cancer who received ICI-based treatment. All patients completed at least three cycles of ICI-based treatment. Pretreatment peripheral blood inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and serum carbohydrate antigen 19-9 (CA19-9) levels were collected. Treatment regimens consisted of ICIs combined with chemotherapy, with or without targeted therapy. Tumor response was assessed using contrast-enhanced CT or MRI according to RECIST version 1.1. PFS was analyzed using the Kaplan-Meier method and Cox proportional hazards regression model. ROC curve analysis was conducted to explore the prognostic efficacy of the above biomarkers. RESULTS: No patient achieved complete response. Among all cases, 17 patients achieved partial response, 51 had stable disease, and 21 experienced progressive disease. The overall objective response rate (ORR) and disease control rate (DCR) were 19.10% and 76.40%, respectively, with no significant difference between the two treatment groups in ORR or DCR (P=0.930 and P=0.954, respectively). Compared to baseline levels, NLR, PLR, SII, and CA19-9 levels were significantly decreased after treatment (all P<0.05), suggesting improved systemic inflammatory status in patients. Kaplan-Meier analysis demonstrated that patients with elevated baseline NLR, PLR, SII, and CA19-9 levels had significantly shorter PFS (P=0.002, P<0.001, P<0.001, and P=0.002, respectively). Univariate Cox regression analysis revealed that poor histologic differentiation (P=0.009), lymph node metastasis (P=0.036), high NLR (P=0.002), high PLR (P=0.001), high SII (P<0.001), and high CA19-9 levels (P=0.002) were correlated with shortened PFS. Multivariate Cox regression analysis further identified poor histologic differentiation (P<0.001), elevated SII (P=0.001), and high CA19-9 levels (P=0.003) as independent adverse prognostic factors for shorter PFS. Most treatment-related adverse events were manageable, and no new safety signals were observed in this cohort. CONCLUSION: ICI combined chemotherapy yields favorable disease control and acceptable safety in patients with advanced gastric cancer. Pretreatment elevated peripheral blood inflammatory markers and CA19-9 levels are associated with poor prognosis, among which SII and CA19-9 were independent risk factors for shortened PFS. Dynamic monitoring of these biomarkers can facilitate clinical risk stratification and individualized treatment decision-making for advanced gastric cancer patients receiving ICI-based therapy.