Prognostic impact of FGFR1 amplification in patients with early-stage resected squamous cell carcinomas of the lung (SQCLC).

Abstract

7559 Background: The spectrum and frequency of oncogenes in squamous cell lung cancers (SQCLCs) has recently been defined. Amplification of fibroblast growth factor receptor 1 (FGFR1) occurs in ~20% of SQCLCs; clinical trials of FGFR1 inhibitors for advanced SQCLCs are ongoing. The frequency, clinicopathologic features, and prognosis of FGFR1 amplification in early-stage, resected SQCLCs have been reported but with discrepant results (Kim et al, J Clin Oncol 2012, Heist et al, J Thorac Oncol 2012). Methods: A cohort of histopathologically-defined and clinically-annotated resected SQCLCs was tested for FGFR1 amplification by FISH (Zytovision Dual Color Probe). Amplification was defined by FGFR1 copy number ≥2.2x CEP8 control copy number and was assessed by two evaluators (MW, LW) who were blinded to clinical results. Disease-free survival (DFS) was defined as date of resection until relapse, recurrence, or death, whichever occurred first. We assessed association between FGFR1status and clinical features (Fisher’s exact test) and DFS (long-rank test). Multivariate DFS analysis was performed using Cox regression analysis. Results: 63 resected SQCLCs were evaluated. FGFR1 amplification was detected in 16 (24%). The median age of the cohort was 70 years (range 48-88). 15 (24%) currently smoked, 47 (75%) former, 1 (1%) never. 7 (11%) received neo-adjuvant therapy. 35 (56%) were stage I, 15 (24%) were stage II, and 13 (20%) were stage IIIA. There was no association between FGFR1 amplification and age (p>0.99), sex (p>0.99), smoking status (p=0.32), or stage of disease (p=0.18). 1-year and median DFS in FGFR1-amplified vs non-amplified cases were 86% vs 71% (p=0.022) and not reached vs 2.3 yrs (95% CI 1.1-3.4 yrs), respectively. Multivariate analysis (FGFR1 status, sex, and stage) found FGFR1amplification significantly associated with improved DFS (HR 3.2, 95% CI 1.1-9.4). Conclusions: In this cohort of resected SQCLCs FGFR1 amplification was associated with improved outcomes. There was no association between FGFR1 status and sex, age, smoking status, or stage. FGFR1 amplification is common in SQCLCs.