title: 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.
authors: Medical Oncology Department, University Hospital Arnau de Vilanova, Avenida Alcalde Rovira Roure, 80, 25198 Lleida, Spain.
authors: Diego
authors: D
authors: Marquez-Medina
authors: Lung Unit, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK.
authors: Sanjay
authors: S
authors: Popat
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D066246:ErbB Receptors
keywords: EGF receptor; ErbB2; ErbB4; adenocarcinoma; afatinib; irreversible; non-small-cell lung cancer; second generation; squamous; tyrosine kinase inhibitor