Clinical characteristics and natural history of patients with squamous cell lung carcinoma with FGFR1 amplification.

Abstract

1533 Background: FGFR1 amplifications have been described as a promising oncogenic target in squamous cell lung cancer. Here we aimed at describing the clinical characteristics and natural history of FGFR1amplified squamous cell lung cancer patients. Methods: From 01/2011 to 01/2012 we screened 553 squamous cell lung cancer patients in our Network for Molecular Screening of Lung Cancer for the presence of FGFR1 amplifications by FISH analysis in accordance with the local ethics committee. FGFR1 was defined as amplified if the ratio of FGFR1 copies to centromeric copies was above 2 or if more than 50% of tumor cells showed 5 copies or if more than 15% of tumor cells demonstrated clusters of FGFR1. Clinical data were collected by extracting information from medical records, the local cancer registry and by questioning treating physicians and patients. Results: FGFR1FISH analysis could be performed in 95% of the cases and was amplified in 16%. Of the amplified cases 75 % were male and 25% female without significant enrichment for male or female. The median age of the patients at diagnosis was 67 yrs (range 46 - 82). Stage at presentation was: 16% I; 17.3% II; 26.7% IIIa, 40% IIIb/IV. 97,3% of the patients were former or active smokers with a median of 40 pack years. The median progression free survival of patients with stage IIIb/IV disease was 11 months (95% CI 8-14; n=14). The median overall survival was not yet reached after a median follow-up time of 14 months (95% CI 11 - 17; n=24). We further screened for co-existing genetic lesions such as mutations in EGFR, BRAF, KRAS, PIK3CA as well as translocations of ALK and amplifications of ERBB2. Two patients demonstrated co-occurring PIK3CA mutations and one a BRAFmutation. Conclusions: Screening for FGFR1 is feasible under routine clinical conditions. By implementation of a regional molecular screening network the ability to screen for FGFR1 amplification was successfully expanded to non-academic centers and private practices. FGFR1 amplifications in squamous cell cancer of the lung are frequent (16%) and associated with smoking history. Screening for FGFR1 might pave the way for the application of new FGFR1 directed targeted drugs in squamous cell lung cancer.