P3.02b-051 Outcome of Advanced EGFR-Mutated NSCLC Patients with MET-Driven Acquired Resistance to EGFR TKI. Results of the METEORE Study: Topic: EGFR Clinical

Abstract

Several mechanisms of acquired resistance to EGFR TKIs have been described including the T790M mutation and MET amplification. Whereas the T790M mutation confers prolonged survival and sensitivity to 3rd generation TKIs, there is no data on outcome and treatment of MET-driven resistant EGFR-mutated NSCLC patients. Molecular and clinico-pathological data from patients with advanced EGFR-mutated NSCLC and MET overexpression or amplification on a post-progression (PP) sample obtained after treatment with EGFR TKI were retrospectively reviewed in 15 nationwide centers. MET overexpression was defined by MET immunochemistry (IHC) score 3+ and MET amplification was assessed by FISH and defined by MET/CEP7 ratio >2 or MET copy number >6 or MET clusters. 43 patients were included (24 del19, 16 L858R and 3 rare EGFR mutations). The median time between EGFR TKI initiation and PP biopsy was 13.8 months [2.1-61.3]. On PP biopsy, 20 tumors tested for FISH (53%) had MET amplification and all out of 37 samples tested for IHC were scored 3+. No epithelial to mesenchymal transformation was observed. A T790M mutation was found in 12/42 (29%) PP biopsies. 5 patients had both MET amplification and T790M mutation. The median overall survival (OS), and the median PP OS were 36.2 months [IC95% 27.3-45.6] and 18.5 months [IC95% 10.6-26.5], respectively. 16 patients received a MET TKI. Objective response was reported in 1 out of 12 evaluable patients treated with a MET TKI as single agent and in 1 of 2 patients treated with a combination of MET and EGFR TKIs. No significant difference was found according to the MET FISH status for OS and PP OS. 3 out of 9 evaluable T790M-positive patients had an objective response upon 3rd generation EGFR TKI. T790M-positive patients had a better OS (median 84.7 vs. 32.2 months, p=0.016) and PP OS (median 36.9 vs. 11 months, p=0.0141) than T790M-negative patients. Even when associated with MET-driven resistance to EGFR TKIs, the T790M mutation may be associated with relative sensitivity to 3rd generation EGFR TKIs and prolonged survival. MET TKIs alone yield low ORR, which emphasizes the need for further evaluation of combinations of EGFR and MET TKIs.