Epidermal growth factor receptor T790M mutation: A major culprit in the progression of epidermal growth factor receptor-driven non-small cell lung cancer and the role of repeat biopsy.

Abstract

Non-small cell lung cancer (NSCLC) accounts for the majority of primary lung cancer cases worldwide. The activating mutations of epidermal growth factor receptor (EGFR) have been demonstrated to associate with the development of NSCLC, with T790M mutation being the most common. Over the years, EGFR tyrosine kinase inhibitors (TKIs) were developed to target EGFR-related mutations. However, patients with activating EGFR mutations who are initially responsive to EGFR-TKIs eventually develop acquired resistance after a median progression-free survival of 10-16 months, followed by disease progression. Recently, the third-generation EGFR inhibitors have emerged as potential therapeutics to block the growth of EGFR T790M-positive tumors. This article reviews the emerging data regarding EGFR mutations and clinical evidence on third-generation agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC. It also reviews the role of repeat biopsy in improving the success rates of treatment of EGFR T790M-derived drug-resistant NSCLC.