Targeted therapies have transformed the management of non–small-cell lung cancer and placed an increased emphasis on stratifying patients on the basis of the presence of oncogenic drivers. The best characterised molecular driver to date is epidermal growth factor receptor. Selective oral inhibitors of epidermal growth factor receptor that are superior to chemotherapy have become available in clinical practice. Unfortunately progression develops after a median of ten to twelve months. This article provides a framework for understanding clinically relevant resistance mechanisms to epidermal growth factor receptor-tyrosine kinase inhibitors and strategies to delay or overcome resistance, both those clinically available and those in development.

(BELG J MED ONCOL 2018;12(2):68–74)