Managing acquired resistance in EGFR-mutated non–small cell lung cancer

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) deliver high response rates with relatively modest toxicity in patients with advanced EGFR-mutated non–small cell lung cancer. Despite this, nearly all tumors eventually develop resistance to first-line therapy. At present, the only standard treatment option for patients with acquired resistance is cytotoxic chemotherapy. In this article, we review the latest research into methods of targeting acquired resistance to EGFR TKI therapy, including third-generation EGFR TKIs that target the T790M resistance mutation and other novel agents in development.