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Durable responses to immunotherapy of non-small cell lung cancers harboring MET exon-14-skipping mutation: A series of 6 cases
- Source :
- Lung cancer (Amsterdam, Netherlands). 150
- Publication Year :
- 2020
-
Abstract
- 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 (10 mutations/Mb) in 3 tested tumors. Four partial and 2 complete responses were obtained during the first 3 months for 5 patients, while pseudoprogression was initially observed in 1. Tolerance was excellent, with only 1 grade-3 immune-related adverse event. Response was maintained for 18-49 months.ICIs could be considered to treat patients whose NSCLCs harbor a METex14 mutation. More biological marker data are needed to identify which patients are most likely to benefit from ICIs.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Oncology
Male
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Pembrolizumab
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
PD-L1
Internal medicine
Carcinoma, Non-Small-Cell Lung
medicine
Humans
Sarcomatoid carcinoma
Aged
Aged, 80 and over
biology
Crizotinib
business.industry
Exons
Middle Aged
medicine.disease
MET Exon 14 Skipping Mutation
Immune checkpoint
respiratory tract diseases
030104 developmental biology
030220 oncology & carcinogenesis
Mutation
biology.protein
Female
KRAS
Immunotherapy
Nivolumab
business
medicine.drug
Subjects
Details
- ISSN :
- 18728332
- Volume :
- 150
- Database :
- OpenAIRE
- Journal :
- Lung cancer (Amsterdam, Netherlands)
- Accession number :
- edsair.doi.dedup.....7f857e56be49300c3ad23090a8c2fcec