High-level FGFR2 Amplification is Associated with Poor Prognosis and Lower Response to Chemotherapy in Gastric Cancers

Abstract Background Recurrent FGFR2 amplification is observed in gastroesophageal cancers but clinical implications are unknown. We investigated the association of FGFR2 amplification with cytotoxic chemotherapy outcome in gastroesophageal cancer (GC) patients. Methods Between 2016 and 2018, we identified 1,045 metastatic GC patients who received palliative fluoropyrimidine/platinum-based chemotherapy and underwent tumor genomic profiling at a tertiary hospital in Korea and two US cancer centers. We retrospectively identified FGFR2-amplified cases and abstracted clinicopathologic features and treatment outcomes. Cox proportional hazard regression model was used to evaluate the variables that demonstrated effects on progression free and overall survival (PFS and OS). Descriptive statistics were used to correlate level of FGFR2 copy number amplification (CNA) and clinicopathological parameters. Results The incidence of FGFR2-amplified GC was 4.0%. A total of 42 FGFR2-amplified GC patients were included and divided into high and lower FGFR2 amplification values. Fifteen patients had an FGFR2 CNA greater than 30, and 27 had a CNA of 30 or less. There was no significant differences between age, sex, tumor localization, Lauren classification, or tumor staging. After a median follow-up duration of 11.4 months, patients with high FGFR2 amplification had significantly poorer median PFS (3.2 vs. 4.8 months, hazard ratio (HR) 2.08, 95% CI, 1.03–4.22, P = 0.042) and significantly shorter median OS (10.1 vs. 26.3 months, HR 2.99, 95% CI = 1.05-8.49, P = 0.040) than the low FGFR2 amplification group. Conclusion Recurrent FGFR2 amplification was observed in roughly 4.0% of GC patients. High FGFR2 amplification was significantly associated with poor progression free survival and overall survival in GC patients. Clinical studies of FGFR2-directed therapies are warranted and should consider stratification by FGFR2 CNA.