EGFR inhibitors as first-line therapy in advanced non-small cell lung cancer

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), erlotinib and gefitinib, are active agents in the treatment of advanced non-small cell lung cancer (NSCLC). Although platinum-based doublet chemotherapy remains the cornerstone for the first-line treatment of metastatic NSCLC, several phase II and III trials have been conducted utilizing EGFR TKIs in this setting. Patients with advanced NSCLC who are life long never-smokers, those with EGFR TK mutations, and those with bronchioloalveolar cell carcinoma histology seem to have promising efficacy with first-line therapy with EGFR TKIs compared with unselected groups of patients receiving the same agents. Phase III trials have clearly demonstrated no improvement in survival when EGFR TKIs were combined with conventional platinum-based doublets, with the exception of subset analysis in nonsmokers. This review will summarize the results of clinical trials on erlotinib or gefitinib in the first-line treatment of select and unselected patients with NSCLC and describe ongoing studies with these agents in NSCLC.