Targeting MET and EGFR in NSCLC—what can we learn from the recently reported phase III trial of onartuzumab in combination with erlotinib in advanced non-small cell lung cancer?

The epidermal growth factor (EGFR) is overexpressed in non-small cell lung cancer (NSCLC), and treatment with erlotinib as monotherapy in patients previously treated with chemotherapy is associated with improved overall survival (OS) (1). However, resistance to tyrosine kinase inhibitors targeting the EGFR is observed in the majority of patients and may be associated with the overexpression and/or amplification of the tyrosine kinase receptor MET (2). Increased MET expression in NSCLC has also been associated with worse prognosis and is co-expressed in 70% of EGFR mutant tumours (2). This data generated a valid rationale for combining MET and EGFR targeted agents in the management of advanced NSCLC.