Durable responses to immunotherapy of non-small cell lung cancers harboring MET exon-14–skipping mutation: A series of 6 cases

•46.2 % (6/13) patients with METex14 mutations response to immunotherapy.•Disease control lasted more than 18 months with partial or complete response.•No predictive factor of response to immunotherapy was identified.•Tolerance profile is that of patients without oncogenic mutations. About 2–3% of non-small–cell lung cancers (NSCLCs) harbor MET exon-14–skipping (METex14) mutations. Efficacy of the MET-inhibitor crizotinib has been reported, but progression-free survival (PFS) was very short. Immune-checkpoint inhibitors (ICIs) have become a cornerstone of NSCLC treatment but appear to be less effective in non-smokers and against tumors exhibiting oncogenic addiction. We describe 6 remarkable (PFS exceeding 18 months) and durable responses to ICIs of NSCLCs harboring a METex14 mutation. Each patient’s clinical and biological characteristics, and tumor responses after ICIs were examined. Complete tumor-DNA sequencing was available after starting second-line ICIs, which followed first-line chemotherapy. Tumor-cell programmed cell-death protein-1 ligand-1 (PD-L1) expression on tumor cells was evaluated using antibody clone E1L3N (Cell Signaling Technology). Among 25 patients with METex14-mutated NSCLCs, 13 of whom were ICI-treated, 6 had prolonged responses: 5 women, 1 man; 57–80 years old; 3 never-smokers, 1 ex-smoker and 2 smokers; 5 adenocarcinomas, 1 sarcomatoid carcinoma; 5 received nivolumab, 1 pembrolizumab. No EGFR, BRAF or KRAS mutations (only 1 minority KRAS mutation), or ALK or ROS translocations were detected. No concurrent MET amplification was observed. Tumor-mutation burden was low (