Abstract

MET exon14 skipping mutation (SM) and high gene copy number (HGCN) are present in 3-4% and ≤1% of NSCLCs. The response to MET inhibitor treatment has been reported in ongoing clinical trials; however, the response to chemotherapy, including immunotherapy, is currently unknown. We conducted a retrospective analysis of patients with MET gene alteration. We collected the clinicopathological data of NSCLC patients with MET gene alteration. The response to chemotherapy was evaluated according to RECIST v1.1. Systemic chemotherapy was given to 10 patients: SM (n=5) and HGCN (n=5). The median age was 67.5 (range 41- 77) years. Thirty percent of the patients were female and 40% were never smokers. The most common histology was adenocarcinoma (40%), followed by pulmonary sarcomatoid carcinoma (20 %). The tumor PD-L1 expression was >50% in 57% (4/7) of the cases and 1-49% in 43% (3/7) of the cases. Platinum doublet, MET inhibitor, immunotherapy (I-O), and I-O+chemotherapy were given to 6, 8, 2 and 1 patients. The overall response rate was 50%, 83%, 0% and 100%, respectively. Hyper-progressive disease after immunotherapy was observed in one patient with SM. The responses to platinum doublet and MET inhibitor treatment were good, while the response to immunotherapy was poor in NSCLC patients with MET gene alteration. MET gene alterations should be identified before the administration of immunotherapy.

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