AUTHOR=Cai Boning , Li Xiaomo , Huang Xiang , Ma Tonghui , Qu Baolin , Yu Wei , Yang Wei , Zhang Pei , Chen Jing , Liu Fang 

TITLE=Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation

JOURNAL=Frontiers in Oncology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.738832

DOI=10.3389/fonc.2021.738832

ISSN=2234-943X

ABSTRACT=Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for advanced non-small-cell lung cancer (NSCLC) patients harboring sensitizing EGFR mutations. However, most patients will eventually develop resistance to EGFR-targeted therapy. Increasing knowledge of de novo and acquired resistance mechanisms allows oncologists to develop mechanism-based therapies to overcome therapeutic resistance. For instance, in EGFR-mutant NSCLC patients with EGFR TKI resistance mediated by MET amplification, the combination therapy of EGFR and MET TKIs has shown promising results in early clinical trials. However, acquired on-target resistance to MET inhibitors forms a formidable challenge to this approach. Here we describe an EGFR-mutant, MET-amplified NSCLC patient who was resistant to first-line erlotinib treatment but responded to the combination targeted therapy of gefitinib plus type 1 MET inhibitor crizotinib after the failure of chemotherapy. After disease progression, molecular testing of the biopsy revealed an acquired MET Y1230H mutation and PD-L1 TPS score of 75%. The patient received a combination treatment regime consisting of gefitinib, type 2 MET inhibitor cabozantinib, and PD-1 antibody pembrolizumab with a prolonged response. Our work suggests that the combination of EGFR TKI with either crizotinib or cabozantinib may serve as the backbone for effective therapeutic options in advanced EGFR-mutant, MET-amplified NSCLC patients.