Predictive value of serum HGF for treatment response to EGFR tyrosine kinase inhibitor in patients with lung adenocarcinoma.

Abstract

7563 Background: EGFR mutation status has emerged to be a validated predictive biomarker for the response to EGFR-tyrosine kinase inhibitors (EGFR-TKI) treatment in non-small cell lung cancer. However, other predictive biomarkers for EGFR-TKI have not been identified. Methods: We retrospectively analyzed the serum concentration of 13 molecules in a cohort of 95 patients (pts) with lung adenocarcinoma who received EGFR-TKI treatment from 3 centers. Pretreatment serum concentrations of HGF, amphiregulin, Beta-cellulin, EGF, sEGFR, Epiregulin, FGF-basic, HB-EGF, PDGF-BB, PIGF, tenascin C, TGF-alpha and VEGF were measured using ELISA and multiplex immunoassay system. Results: Serum concentrations of HGF and VEGF differ significantly between pts with progressive-disease (PD) and those without PD (HGF, p<0.0001, VEGF, p<0.0001). HGF and VEGF were strongly associated with progression free survival (PFS) and overall survival (OS) in univariate Cox analysis (all tests for hazard ratio [HR] showed p<0.0001). In multivariate Cox analysis stratified by EGFR mutation status (mutant, n=20 /wild-type, n=23 /unknown, n=52), high concentration of HGF showed a shorter PFS and OS independently of significant clinical variables including gender and PS (Table). Conclusions: Serum HGF is closely related with clinical outcomes of EGFR-TKI treatment and it raise the possibility of further refinement for the selection of patients in combination with EGFR mutation status. Our findings warrant further investigations in a prospective study to evaluate whether HGF is a predictive/prognostic biomarker for EGFR-TKI. Multivariate analysis stratified by EGFR mutation status (n = 95); HGF and VEGF were logtransformed Progression-free survival HR 95% CI P HR 95% CI P Gender M vs. F 1.28 (0.77-2.15) 0.34 1.72 (0.96-3.10) 0.07 PS 2-4 vs. 0-1 0.64 (0.36-1.12) 0.11 1.52 (0.86-2.66) 0.15 HGF 6.28 (2.65-14.9) <0.0001 2.78 (1.28-6.01) <0.0001 VEGF 1.94 (1.11-3.39) 0.0204 1.60 (0.85-3.02) 0.15 No significant financial relationships to disclose.