Abstract
BACKGROUND: There is currently no effective targeted therapy for advanced HER2-negative gastric cancer (GC). While immunotherapy combined with chemotherapy is the first-line treatment for GC, patient survival outcomes remain highly heterogeneous, highlighting the urgent need for reliable predictive biomarkers. The fibrinogen-to-albumin ratio (FAR) integrates both inflammation (elevated fibrinogen levels) and nutritional status (reduced albumin levels). Although FAR has been associated with immunotherapy resistance in various solid tumors, its prognostic value in GC patients receiving immunochemotherapy remains unclear. AIM: To assess the predictive value of the FAR in the long-term prognosis of advanced HER2-negative GC patients receiving sintilimab-based immunotherapy combined with chemotherapy. METHODS: This retrospective study included 260 patients with unresectable or metastatic HER2-negative GC who received sintilimab plus chemotherapy from 2021 to 2024. Pre-treatment FAR values were calculated, and the optimal cutoff value was determined using receiver operating characteristic curve analysis. The association between the FAR and overall survival (OS) and progression-free survival (PFS) was analyzed using Kaplan-Meier survival curves and Cox proportional hazards models. Independent prognostic factors were identified by multivariate Cox regression analysis based on OS, and a nomogram model was constructed incorporating FAR. The concordance index (C-index) and calibration curves were used to assess the predictive performance and calibration of the model. RESULTS: Patients with high FAR (≥ 0.08) had significantly shorter median PFS [7.80 months (6.40-8.30) vs 10.00 months (9.30-11.20), P < 0.001] and OS [14.20 months (12.20-16.60) vs 19.50 months (18.80-22.00), P < 0.001] compared to the group with low FAR (< 0.08). Moreover, the group with high FAR had a significantly lower objective response rate (10.22% vs 19.51%, P = 0.034) and disease control rate (34.31% vs 49.59%, P = 0.013). The incidence of adverse events did not significantly differ between the two groups (P > 0.05). Multivariate analysis confirmed the FAR as an independent prognostic factor for OS (HR = 2.33, 95%CI: 1.59-3.43, P < 0.001). The nomogram model, incorporating FAR, Eastern Cooperative Oncology Group performance status, programmed cell death ligand 1 expression, tumor stage, and body mass index, demonstrated strong predictive accuracy, with an internal validation C-index of 0.73 (95%CI: 0.66-0.79). The calibration curve showed a high consistency between predicted and actual survival rates. CONCLUSION: Patients with low FAR had significantly better prognostic outcomes than those with high FAR when receiving immunochemotherapy. Thus, FAR may serve as a valuable prognostic biomarker for predicting survival outcomes in patients with advanced HER2-negative GC.