EGFR, EGFR TKI, and EMSI: a never-ending story

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) such as gefitinib and erlotinib are the first generation of EGFR inhibitors that were developed more than a decade ago. Beginning with the disappointing results of phase III trials that combined EGFR TKIs with chemotherapy in unselected patients with non-small cell lung cancer (NSCLC) (IDEAL-I and IDEAL–II for gefitinib, TALENT and TRIBUTE for erlotinib), both TKIs had a history of ups (BR.21 for erlotinib, INTEREST for gefitinib) and downs (ISEL for gefitinib), until the recent success of pivotal studies comparing EGFR TKIs to doublet chemotherapy in patients with activating EGFR mutations (IPASS, NEJ002 and WJTOG3405 for gefitinib, OPTIMAL and EURTAC for erlotinib).