title: AZD9291 in EGFR-mutant advanced non-small-cell lung cancer patients.
abstract: Non-small-cell lung cancer (NSCLC) patients whose tumors have an EGFR-activating mutation develop acquired resistance after a median of 9-11 months from the beginning of treatment with erlotinib, gefitinib and afatinib. T790M mutation is the cause of this resistance in approximately 60% of cases. AZD9291 is an oral, irreversible, mutant-selective EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) developed to have potency against EGFR mutations, including T790M mutation, while sparing wild-type EGFR. A Phase I trial of AZD9291 in EGFR-mutant NSCLC patients, demonstrated high activity, essentially among T790M-mutant tumors, with a manageable tolerability profile. Ongoing Phase III trials are evaluating AZD9291 in EGFR-mutant patients as first-line treatment compared with erlotinib and gefitinib; and as second-line treatment compared with chemotherapy after progression on EGFR TKI in T790M-mutant tumors. Better identification of T790M-mutant tumors post EGFR TKI relapse and mechanisms of resistance to AZD9291 are the future challenges. This article reviews the emerging data regarding AZD9291 in the treatment of patients with advanced NSCLC.
authors.affiliation: Gustave Roussy, Medical Oncology Department, Villejuif, France.
authors.forename: Jordi
authors.initials: J
authors.lastname: Remon
authors.affiliation: Gustave Roussy, Medical Oncology Department, Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Planchard
mesh_terms: D000178:Acrylamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D019233:Retreatment; D016896:Treatment Outcome; D007211:Indoles; D011743:Pyrimidines
chemical_list: D000178:Acrylamides; D000814:Aniline Compounds; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; C000596361:osimertinib; D007211:Indoles; D011743:Pyrimidines
keywords: AURA; AZD9291; EGFR mutant; non-small-cell lung cancer