Abstract 557: Noninvasive analysis of acquired resistance to EGFR-TKI

Abstract

Abstract BACKGROUND Epidermal growth factor receptor (EGFR) T790M mutation is associated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) resistance in non-small cell lung cancer (NSCLC). However, the tissue availability limits the genotyping of EGFR T790M mutation in the clinical setting. The aims of this study are to develop a blood-based, non-invasive approach to detect the EGFRT790M mutation in advanced NSCLC patients. Additionally, plasma concentrations of HGF, MET and amphiregulin which are also resistant factors of EGFR-TKIs EXPERIMENTAL DESIGN Plasma sample were collected from NSCLC patients with activating EGFR mutations, who had resistant to EGFR-TKIs treatment. EGFR T790M mutations were detected using droplet-digital PCR (ddPCR) system from plasma DNA at resistance to EGFR-TKI. Plasma concentrations of HGF, soluble MET (sMET) and amphiregulin were determined using enzyme-linked immunosorbent assay. The relationships between the EGFR T790M mutation status and the plasma concentrations, progression-free survival (PFS) overall survival (OS) were analyzed. RESULTS Twenty-one (35%) of the patients had EGFR T790M mutation in plasma DNA using ddPCR system. The levels amphiregulin tended to be increased at the resistance in the patients with EGFR T790M mutation. The PFS and OS of the patients with EGFR T790M mutation was significantly shorter than that of the patients without EGFR T790M mutation (P =0.03 and 0.04). The PFS of the patients who had high amphiregulin at the resistance and the OS of the patients who had high amphiregulin at pre-treatment were shorter than these of t low amphiregulin (P = 0.05 and 0.05) CONCLUSIONS The ddPCR system is a detectable method for determining the plasma EGFR T790M mutation status. The combination of EGFR T790M mutation status by ddPCR and the amphiregulin levels may aid in monitoring drug resistance and in predicting a prognosis. Citation Format: Hideharu Kimura, Makoto Nishio, Tsutomu Daito, Kazuto Nishio. Noninvasive analysis of acquired resistance to EGFR-TKI. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 557. doi:10.1158/1538-7445.AM2014-557