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Ref Type Journal Article
PMID (33335011)
Authors Roth KG, Mambetsariev I, Salgia R
Title Prolonged survival and response to tepotinib in a non-small-cell lung cancer patient with brain metastases harboring MET exon 14 mutation: a research report.
Journal Vol Issue Date Pages Journal Short Title
Cold Spring Harbor molecular case studies 6 6 2020 Dec Cold Spring Harb Mol Case Stud
URL
Abstract Text Tyrosine kinase inhibitors (TKIs) have transformed the standard of care in lung cancer. A number of TKIs have been discovered that specifically target oncogenes, including MET receptor tyrosine kinase. Second-generation MET TKIs are showing improved efficacy over first-generation TKIs. Herein, we report a case of a patient with metastatic lung adenocarcinoma harboring a MET exon 14 splice site mutation who has had prolonged disease control by a second-generation MET-TKI tepotinib. A 66-yr-old man was diagnosed with stage IV lung adenocarcinoma. He was started on carboplatin, paclitaxel, and bevacizumab, but had severe toxicity. He was switched to pembrolizumab as his tumor was PD-L1 70%, and molecular testing was not yet performed because of insufficient tissue. A bronchoscopy with endobronchial ultrasound was performed and a MET exon 14 splice site mutation was detected by next-generation sequencing. Upon progression, he was then enrolled in a clinical trial of tepotinib and continues with stable disease for more than 45 cycles and 31 mo. The MET receptor tyrosine kinase and the ligand hepatocyte growth factor (HGF) have been implicated as oncogenes and drivers of non-small-cell lung cancer (NSCLC). Newer MET TKIs including capmatinib and tepotinib more recently showed not only improved localized control and response, but early data suggests intracranial activity as compared to first-generation MET TKIs, both in the front-line and the refractory setting. This is a case report demonstrating an effective duration of response in a patient with widely metastatic lung adenocarcinoma harboring a MET exon 14 mutation.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CD274 positive lung adenocarcinoma sensitive Pembrolizumab Case Reports/Case Series Actionable In a clinical case study, a patient with CD274 (PD-L1)-positive (70% tumor cells) metastatic lung adenocarcinoma treated with Keytruda (pembrolizumab) achieved a complete response in multiple brain metastases prior to disease progression in a primary lung lesion after 9 months of treatment, but was subsequently treated with Tepmetko (tepotinib) due to the presence of a MET exon 14 skipping mutation, which resulted in prolonged disease stabilization with no recurrence of brain lesions (PMID: 33335011). 33335011