Diagnosis and treatment of non-small cell lung cancer (NSCLC) harboring MET Ex14 skipping: have we met the desired drug?

Abstract

In 2006, the MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping mutation (METex14 skipping) was reported as a new driver gene abnormality in approximately 3% of patients with non-small cell lung cancer (NSCLC) (1). This mutation affects both sexes equally and is present in young non-smokers, elderly individuals, and smokers. Furthermore, it also has been identified in 8–17% of sarcomatoid carcinoma (2-4). In March 2020, the MET inhibitor tepotinib was approved in Japan, and capmatinib was approved in June of the same year. The U.S. Food and Drug Administration (FDA) approved capmatinib in May 2020 and tepotinib in February 2021 (5). Therefore, detection of this mutation is crucial for all patients with advanced NSCLC. This review provides an overview of MET and MET receptor tyrosine kinases, the results of pivotal clinical trials (VISION and GEOMETRY mono-1 trials) on MET-tyrosine kinase inhibitors (Table 1), and the testing systems used for the genetic diagnosis of METex14 skipping.