Negative results of METLung study: an opportunity to better understand the role of MET pathway in advanced NSCLC

The negative results of the global METLung phase III trial recently presented at American Society of Clinical Oncology (ASCO) were clearly unexpected (1). The trial assessed the impact on overall survival (OS) of adding onartuzumab, a monovalent monoclonal antibody against mesenchymal-epithelial transition (MET) factor receptor tyrosine kinase (RTK), to erlotinib in second or third-line therapy of advanced non-small cell lung cancer (NSCLC) patients with MET overexpression. There was a strong rationale behind this phase III trial: dysregulation of MET signaling in cancer is responsible for cell proliferation, cell cycle progression, cell dissociation, motility, spreading and invasion, overexpression of MET is linked to a worse prognosis for both early and late stages of NSCLC, and crosstalk with other RTKs including EGFR can lead to synergistic activation of downstream pathways. Moreover, amplification of MET seems to be involved in a significant proportion of patients with EGFR mutations developing acquired resistance to EGFR inhibitors.