Afatinib: a second-generation EGF receptor and ErbB tyrosine kinase inhibitor for the treatment of advanced non-small-cell lung cancer

Abstract

First-generation reversible EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs) changed our understanding of advanced non-small-cell lung cancer biology and behavior. The presence of sensitizing EGFR mutations in advanced non-small-cell lung cancer defines a subset of patients with a better prognosis and sensitivity to EGFR-TKIs with a better response rate, progression-free survival, quality of life and symptom control than with chemotherapy in the first-line therapy setting. However, current EGFR-TKIs show minimal responses in EGFR wild-type patients or with acquired TKI resistance mediated through the EGFR T790M allele. Afatinib is an irreversible pan-ErbB-TKI, active against wild-type EGFR, sensitizing and T970M-mutant EGFR, ErbB2 and ErbB4 receptors, and represents a step change between reversible first-generation and future irreversible highly specific third-generation EGFR-TKIs. Here, we review the clinical development of afatinib through the LUX-Lung trials portfolio highlighting benefits and toxicities.

Keywords: EGF receptor; ErbB2; ErbB4; adenocarcinoma; afatinib; irreversible; non-small-cell lung cancer; second generation; squamous; tyrosine kinase inhibitor.