title: Afatinib for the treatment of advanced non-small-cell lung cancer.
abstract: BACKGROUND
  The inhibition of the epidermal growth factor receptor (EGFR) through tyrosine kinase inhibitors (TKIs) represents an effective strategy for EGFR-mutated NSCLC. Afatinib is an irreversible erythroblastosis oncogene B (ErbB) family blocker, able to inhibit the kinase domains of EGFR, HER2 and HER4, and the transphosphorylation of ErbB3 that has recently been approved in the United States for the first-line treatment of EGFR-mutated NSCLC and in Europe and Japan for the treatment of EGFR-mutated TKI-naive patients.
  
  
  METHODS
  The authors analyzed the pharmacology and the clinical activity of afatinib in NSCLC through a review of the literature. Trials exploring different settings have been reported, including LUX-Lung 3 and LUX-Lung 6, where the drug achieved better outcomes in terms of response rate, progression-free survival and quality of life compared with chemotherapy. The main toxicities of afatinib are gastrointestinal and skin-related adverse events.
  
  
  CONCLUSIONS
  Afatinib showed remarkable efficacy as a first-line treatment in the presence of common EGFR mutations. Afatinib showed some activity in NSCLC with acquired resistance to EGFR TKIs, although, currently, its efficacy after the failure of erlotinib or gefitinib has not been clearly stated. Direct clinical data comparing the activity and tolerability of different inhibitors are still needed.
authors.affiliation: UOS Tumori Polmonari, IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro , L.go Benzi 10, Genova 16132 , Italy carlo.genova1985@gmail.com.
authors.forename: Carlo
authors.initials: C
authors.lastname: Genova
authors.forename: Erika
authors.initials: E
authors.lastname: Rijavec
authors.forename: Giulia
authors.initials: G
authors.lastname: Barletta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Burrafato
authors.forename: Federica
authors.initials: F
authors.lastname: Biello
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Dal Bello
authors.forename: Simona
authors.initials: S
authors.lastname: Coco
authors.forename: Anna
authors.initials: A
authors.lastname: Truini
authors.forename: Angela
authors.initials: A
authors.lastname: Alama
authors.forename: Francesco
authors.initials: F
authors.lastname: Boccardo
authors.forename: Francesco
authors.initials: F
authors.lastname: Grossi
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D066246:ErbB Receptors