Epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer: a decade of progress and hopeful future
Nearly 50% of patients with non-small cell lung cancer (NSCLC) are found to have metastatic disease at presentation (1). Platinum doublet chemotherapy remains the standard initial therapy for a vast majority of patients with advanced NSCLC who have a good performance status. Approximately 10% of patients with advanced NSCLC have activating mutations in the epidermal growth factor receptor tyrosine kinase (EGFR TK) in the tumor tissues (2). Significant progress has been made in the use of molecularly targeted therapies in lung cancer since the initial discovery linking the presence of certain EGFR TK mutations with exquisite responsiveness to EGFR tyrosine kinase inhibitor (TKI) gefitinib (3,4). Although erlotinib, another EGFR TKI, has been approved for use in patients with advanced NSCLC who have progressive disease after platinum based therapy based on the randomized study sponsored by the National Cancer Institute (NCI)-Canada, it is evident now that the impressive clinical benefit from EGFR TKIs is seen almost exclusively in patients whose tumor cells demonstrate specific mutations in the EGFR TK domain (5).