EGFR tyrosine kinase inhibitors as first-line therapy in advanced EGFR mutation-positive non-small cell lung cancer: strategies to improve clinical outcome

The epidermal growth factor receptor (EGFR) has been established as a clinically relevant target for the treatment of patients with advanced non-small cell lung cancer (NSCLC) (1). EGFR blockade can be achieved by either monoclonal antibodies directed against the surface of the receptor or tyrosine kinase inhibitors directed against the intracellular domain of the receptor (1,2). Monoclonal antibodies such as cetuximab and necitumumab improved outcome including overall survival, particularly in patients with squamous cell NSCLC and/or high EGFR expression or EGFR fluorescence in situ positivity (3-7). EGFR tyrosine kinase inhibitors (TKIs) have also been established for the treatment of patients with advanced NSCLC (1). While these TKIs show efficacy in non-oncogene-driven NSCLC, they have much higher efficacy in patients who harbour EGFR mutations in their tumours. EGFR mutations occur in tumours of about 40% of Asian patients and 15% of Caucasian patients with advanced NSCLC (8). Based on the results from several randomized phase 3 trials, EGFR TKIs have been established as first-line therapy in patients with advanced EGFR mutation-positive NSCLC (1).