Targeting MET exon 14 skipping mutations in non-small cell lung cancer

MET exon 14 skipping mutation (MET∆ex14) is present in about 3% of non-small cell lung cancers (NSCLCs). Recently, two MET-tyrosine kinase inhibitors (capmatinib and tepotinib) demonstrated their clinical potential in the treatment of this subgroup of NSCLC patients resulting in their FDA approval (EMA approval pending). In their respective pivotal trials, these agents have yielded a promising median progression-free survival (PFS) of 8-12 months. Unfortunately, however, it has also been reported that a third to half of patients show inherent resistance to MET-TKIs. Furthermore, the emergence of acquired resistance to MET-TKIs is inevitable. This article will summarize the clinical trial data generated with capmatinib and tepotinib in this setting after which some insights into the inherent and acquired resistance mechanisms to MET-TKIs will be addressed.