The identification of clinically relevant driver mutations has reshaped the therapeutic landscape of non-small cell lung cancer (NSCLC). In the past year, the activation of the mesenchymal-to-epithelial transition (MET) pathway has gained importance because of the recent development of selective and effective MET inhibitors. In NSCLC, MET dysregulation may be caused either by mutation or amplification and is associated with poor prognosis. In addition, the optimal first-line treatment is currently undetermined since data from different trials suggest limited activity of immune checkpoint inhibitors, indicating a high medical need. In phase II trials, MET inhibitors have shown promising response rates (41–65%) and duration of response in MET exon 14 mutated NSCLC. First-line trials are currently ongoing. In de novo MET amplified NSCLC, the activity of these inhibitors seems limited to tumours with a high level amplification. As in other oncogene driven NSCLC, resistance mechanisms do appear ultimately and future research should focus on this in order to optimise treatment options for MET dysregulated NSCLC.

(BELG J MED ONCOL 2021;15(6):278-82)