title: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer.
abstract: OBJECTIVE
  Patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) develop resistance during therapy with EGFR tyrosine kinase inhibitors (TKIs). In about half of the patients, this resistance is because of the emergence of the T790M mutation. Third-generation TKIs are active against EGFR-activating mutations and the T790M resistance mutation and have only limited efficacy against wild-type EGFR. Here we review the current status of the clinical development of these novel TKIs.
  
  
  RESULTS
  Third-generation TKIs in clinical development include osimertinib, rociletinib, and HM61713. Osimertinib and rociletinib have shown clinical efficacy in phase I/II trials in patients who had acquired resistance to first- or second-generation TKIs. Both TKIs are currently further evaluated in phase III trials as first-line or second-line therapy in patients with advanced EGFR mutation-positive NSCLC. HM61713 is in early clinical development.
  
  
  CONCLUSIONS
  Third-generation EGFR TKIs have shown activity in patients with acquired resistance to first- and second-generation EGFR TKIs and may further improve clinical outcome in patients with advanced EGFR mutation-positive NSCLC.
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Pirker
mesh_terms: D000178:Acrylamides / Q000627:therapeutic use; D000814:Aniline Compounds; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D009154:Mutation / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D007211:Indoles
chemical_list: D000178:Acrylamides; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C000596361:osimertinib; D007211:Indoles; C000589977:rociletinib; C512478:EGFR protein, human