title: Osimertinib, a third-generation tyrosine kinase inhibitor targeting non-small cell lung cancer with EGFR T790M mutations.
abstract: Oncogenic driver mutations in the epidermal growth factor receptor (EGFR) gene have provided a focus for effective targeted therapy. Unfortunately, all patients eventually develop resistance to frontline therapy with EGFR tyrosine kinase inhibitors (TKIs). The majority of patients develop a large subclonal population of tumor cells with a T790M mutation that renders these cells resistant to first-generation TKIs. Osimertinib is a third-generation EGFR TKI that was designed to overcome resistance from T790M mutations. This agent has demonstrated strong preclinical activity, and in the clinic it has demonstrated a high objective response rate and progression-free survival in patients with EGFR double mutations (L858R/T790M and exon 19 deletion/T790M). It is now approved by the FDA for patients who have a documented T790M mutation and who have progressed on a prior TKI. Osimertinib is also approved in the E.U. and Japan.
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: McCoach
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. antonio.Jimeno@UCDenver.edu.
authors.forename: A
authors.initials: A
authors.lastname: Jimeno
mesh_terms: D000178:Acrylamides; D000814:Aniline Compounds; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D007211:Indoles; D011743:Pyrimidines
chemical_list: D000178:Acrylamides; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; C000596361:osimertinib; D007211:Indoles; D011743:Pyrimidines; C512478:EGFR protein, human
keywords: EGFR; Osimertinib; T790M; Tyrosine kinase inhibitor