Identifying and Targeting MET Alterations in NSCLC

Lung cancer is ranking no.1 in top 10 causes of cancer death in Taiwan. Non-small cell lung cancer (NSCLC) is a subtype of the most frequently diagnosed lung cancer. With an increasing understanding of NSCLC biology, new diagnostic and therapeutic strategies have been developed to identify driver mutations and NSCLC is further characterized by molecularly defined subsets actionable with targeted therapies.

Therapeutic strategies targeting EGFR, ALK, ROS1, and other driver oncogenes have revolutionized the treatment landscape of NSCLC. Recently, MET exon 14 skipping (METex14) has joined the group of actionable driver mutations. METex14 skipping occur in 3-4% of all NSCLC patients, result in constitutive activation of the MET receptor by altering a region required for receptor degradation. Multi-kinase inhibitor of MET, such as crizotinib, and more recently selective MET inhibitors, such as tepotinib and capmatinib, have demonstrated clinical efficacy and safety in clinical trials. These results have led to the approval of MET inhibitors by TFDA.

The other alteration in MET is amplification. MET amplification plays an important role in the development of NSCLC either de novo or in resistance to epidermal growth factor receptor tyrosine–kinase inhibitor (EGFR-TKI) settings. Emerging data are developed to demonstrate the clinical benefit of selective MET inhibitors in MET amplification.

With more evidence, treatment landscape for MET alterations in NSCLC will be largely updated to improve treatment outcomes and precision medicine will also be highlights to optimize treatment strategies.