title: Advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations: first-line treatment with afatinib and other EGFR TKIs.
abstract: Based on the results of several randomised controlled trials, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have now replaced platinum-based chemotherapy as first-line therapy for advanced non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation. Areas covered: This review describes the EGFR pathway and its abnormalities in NSCLC and discusses the differential molecular and clinical activity of first and next-generation EGFR TKIs in the first-line treatment of tumors with an activating EGFR mutation, with a special focus on the second-generation agent afatinib. A comprehensive literature search was conducted to identify all relevant clinical trials including abstracts from most recent meetings to provide up-to-date information on this topic. Expert commentary: While the first-generation EGFR TKIs erlotinib and gefitinib exhibited good tolerability and improved progression-free survival compared with a platinum doublet, they failed to improve overall survival (OS). In contrast, clinical trials of afatinib (LUX-Lung 3 and 6) demonstrated a significant OS advantage over a platinum doublet, particularly in patients whose tumors harbored the Del19 mutation. Moreover, in a head-to-head comparison afatinib improved efficacy versus gefitinib in patients with common EGFR mutations across a range of clinically relevant endpoints. Afatinib is therefore a promising first-line option in these patients.
authors.affiliation: a Department of Respiratory Medicine, Allergology and Sleep Medicine , Paracelsus Medical University, General Hospital Nuernberg , Nuremberg , Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brückl
authors.affiliation: b Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology Centre Munich , Ludwig-Maximilians Universität München , Munich , Germany.
authors.forename: Amanda
authors.initials: A
authors.lastname: Tufman
authors.affiliation: b Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology Centre Munich , Ludwig-Maximilians Universität München , Munich , Germany.
authors.forename: Rudolf Maria
authors.initials: RM
authors.lastname: Huber
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D066246:ErbB Receptors
keywords: Afatinib; EGFR; NSCLC; erlotinib; gefitinib; mutation-positive