Abstract
BACKGROUND: Current standard of care for squamous non-small cell lung cancer (sqNSCLC) is not very effective, and FGFR2b-targeted therapy may be a new option for patients with sqNSCLC. The prevalence and clinical implications of fibroblast growth factor receptor 2b (FGFR2b) expression in Chinese patients with advanced sqNSCLC remain poorly characterized. This study evaluated FGFR2b expression patterns, their association with programmed death-ligand 1 (PD-L1) expression, and clinical outcomes in this population. METHODS: This retrospective cross-sectional analysis screened three hundred newly diagnosed advanced sqNSCLC patients from 2018 to 2024. Archival biopsy samples were assessed for FGFR2b expression via immunohistochemistry (IHC). A total of 266 patients, with histologically confirmed stage IIIB-IV sqNSCLC and valid FGFR2b protein expression status, were enrolled. Historical clinical data and PD-L1 detection reports were extracted from hospital records. RESULTS: Among the 266 patients, 117 (44.0%, 117/266) were diagnosed with IIIB/IIIC-stage cancer, and 149 (56%, 149/266) were diagnosed with IV-stage cancer. FGFR2b positivity (≥1+ in ≥1% tumor cells) was observed in 50.8% of patients, while overexpression (≥2+ in ≥1% tumor cells) occurred in 19.5%. FGFR2b expression was correlated significantly with sex (P=0.04), and cancer stage (P=0.01). Among 204 patients with valid FGFR2b and PD-L1 dual expression data, over 80% of FGFR2b-positive tumors demonstrated concurrent PD-L1 expression. In patients receiving first-line paclitaxel/nab-paclitaxel-platinum combined with anti-programmed cell death-1 (PD-1)/PD-L1 antibodies, FGFR2b-positive cohorts exhibited superior outcomes: higher objective response rate (57.4% vs. 41.9%) and prolonged median progression-free survival {11.3 months [95% confidence interval (CI): 6.6-17.9] vs. 6.5 months (95% CI: 5.0-17.3)} compared to FGFR2b-negative counterparts. CONCLUSIONS: FGFR2b expression may serve as a predictive biomarker for therapeutic response of FGFR2b-targeted agents in sqNSCLC. The high co-expression rate of FGFR2b and PD-L1 supports the feasibility of combining FGFR2b-targeted agents with immune checkpoint inhibitors as a rational treatment strategy.