title: Dacomitinib, a new therapy for the treatment of non-small cell lung cancer.
abstract: BACKGROUND
  Advanced or metastatic non-small cell lung cancer (NSCLC) is characterized by a poor prognosis and few second- or third-line treatments. First-generation reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibition (TKI) has paved the way for targeted treatment in lung cancer. These drugs result in excellent responses in patients with activating EGFR mutations. Unfortunately, resistance often develops. Second-generation irreversible inhibitors hope to prevent mutational progression to a resistant clone or delay the use of alternative non-targeted therapies.
  
  
  METHODS
  This article focuses on the current published ongoing research using the second-generation irreversible TKI, dacomitinib . The use of dacomitinib, a pan inhibitor of the HER family of tyrosine kinases, will be reviewed along with its efficacy in the advanced or metastatic NSCLC population.
  
  
  CONCLUSIONS
  Data available suggest dacomitinib is effective in NSCLC patients both in initial treatment and after failure of first-generation inhibitors. Furthermore, preclinical data suggest dacomitinib can achieve responses in tumors harboring the T790M, gatekeeper mutation, present in up to 50% of tumors that have acquired resistant to first-generation inhibitors. Its usefulness in potentially delaying development of resistant clones as well as in combination with other targeting strategies is under investigation.
authors.affiliation: Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20889, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Brzezniak
authors.forename: Corey A
authors.initials: CA
authors.lastname: Carter
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D052999:Quinazolinones; C525726:dacomitinib; D066246:ErbB Receptors