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MET exon 14 skipping mutation in triple-negative pulmonary adenocarcinomas and pleomorphic carcinomas: An analysis of intratumoral MET status heterogeneity and clinicopathological characteristics
Dohee Kwon, Jaemoon Koh, Sehui Kim, et al.
Commentary by Stefan Zimmermann
Our understanding of MET as an actionable target, more specifically MET exon 14 skipping alterations, found in 3% of both non-squamous and squamous advanced NSCLC, has allowed the use of crizotinib and the development of newer MET inhibitors. Yet much remains unknown regarding the clinicopathological characteristics of these tumors. In this series of 147 triple negative (EGFR-, ALK-, and KRAS-) carcinomas, 8.8% of adenocarcinomas and 20% of pleomorphic carcinomas harbored were METex14+. In contrast to EGFR mutations, the MET mutation rate was independent of ethnicity, the alteration was observed in older individuals (median age 73), and there was no statistical association with smoking status. This is an important reminder to screen patients, including older individual with acinar adenocarcinoma and pleomorphic carcinoma. Indeed, after the failure of several high-profile trials, the development of MET TKIs is regaining momentum with tepotinib (NCT02864992), savolitinib (NCT02897479), capmatinib (NCT02750215), glesatinib (NCT02544633) and merestinib (NCT02920996)!