Abstract

Purpose
Fibroblast growth factor receptor 2b (FGFR2b) is a promising therapeutic target in gastric cancer; however, its clinical relevance in immune checkpoint inhibitor (ICI)-based chemotherapy remains unclear. Therefore, this study aims to evaluate the expression pattern and predictive value of FGFR2b in patients undergoing first-line nivolumab plus chemotherapy.
Materials and Methods
This single-center study included 503 patients diagnosed with gastric cancer. Among them, 296 underwent nivolumab-chemotherapy, while 207 underwent chemotherapy alone. FGFR2b expression was assessed via immunohistochemistry using samples collected after mid-2022. FGFR2b positivity was defined as membranous staining intensity of 2+/3+ in ≥ 1% of tumor cells, with ≥ 10% as overexpression, and 1–9% as low expression.
Results
FGFR2b overexpression and positivity were identified in 9.3% and 18.7% of cases, respectively. Discordance between paired biopsy and surgical samples was observed (20.0% and 40.0% for overexpression and positivity, respectively), indicating marked intratumoral heterogeneity. Among patients who underwent nivolumab-chemotherapy, FGFR2b overexpression and low expression were associated with favorable survival trends compared to those of FGFR2b-negative cases. These associations were not observed in patients treated with chemotherapy alone. Compared to chemotherapy alone, nivolumab-chemotherapy was associated with a greater survival benefit in patients with FGFR2b positivity. Multivariate interaction analyses revealed a significant interaction between FGFR2b expression and nivolumab-based chemotherapy.
Conclusion
FGFR2b expression exhibits substantial intratumoral heterogeneity in gastric cancer and may be linked to favorable outcomes in patients undergoing first-line ICI plus chemotherapy. Therefore, future studies should validate this finding, along with mechanistic investigations.

• Keywords: Stomach neoplasms, FGFR2b, Nivolumab, Antineoplastic combined chemotherapy protocols, Predictive biomarker