Abstract 4576: Combination of a label independent CTC enrichment platform with fluorescence in situ hybridization for the molecular characterization of CTCs in non-small cell lung cancer patients

Abstract

Abstract Background: Patients with EGFRmt non-small cell lung cancer (NSCLC) develop resistance to first (erlotinib/ gefitinib) and second (afatinib) generation EGFR tyrosine kinase inhibitors (EGFR TKIs). Circulating tumor cells (CTCs) may be used as a potential biological material to monitor genetic alterations during the clinical course of the disease. We used the ParsortixTM (ANGLE) system, a label-independent microfluidic-based technology platform, to enrich CTCs from whole blood of NSCLC patients to evaluate the presence of HER-2 and c-MET amplification using fluorescence in situ hybridization (FISH). Materials and methods: Peripheral blood (PB) (15mL) from 42 patients with EGFRmt and resistant to 1st and 2nd generation EGFR TKIs NSCLC was obtained before, during and after treatment with osimertinib. CTCs were isolated using the ParsortixTM system and were further analyzed for HER-2 and c-MET amplification by FISH. Results: PB samples were obtained before (n=42), after one cycle (n=12) and at PD (n=7) during treatment with Osimertinib. One patient had HER-2 amplified CTCs whereas in total, 5 patients had marginally HER-2-positive CTCs; HER-2-positive CTCs were observed in 1/42 baseline sample but in none post-1st cycle and PD samples. Similarly, c-MET amplification was detected in 3/42 patients at baseline whereas in total 4 patients had marginally c-MET-positive CTCs. Treatment with Osimertinib resulted in a decrease of the number of c-MET amplified CTCs in these patients. In all c-MET and HER-2 amplified CTCs there was no HER-2 or c-MET amplification in the primary tumor. c-MET amplification in the primary tumor was detected only in one patient, however this patient had no detectable CTCs. Conclusions: Our preliminary results indicate that in selected patients with EGFRmt NSCLC, detection of HER-2 or c-MET amplified CTCs may be correlated with tumor resistance to EGFR TKIs. The ParsortixTM system can be successfully combined with downstream FISH analysis for the molecular characterization of CTCs in NSCLC patients. More samples are currently being analyzed in order to reveal the implication of HER-2 and c-MET amplification in resistance to therapy with first, second and third generation EGFR TKIs. Citation Format: Aliki Ntzifa, Martha Zavridou, Pavlos Pollakis, Georgia Bardi, Vasilis Georgoulias, Athanasios Kotsakis, Evi Lianidou. Combination of a label independent CTC enrichment platform with fluorescence in situ hybridization for the molecular characterization of CTCs in non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4576.