title: [Management of patients with resistance to EGFR-TKI].
abstract: Patients presenting with non-small cell lung cancer (NSCLC) and active EGFR mutation have a high response rate (60-70%) to EGFR tyrosine kinase inhibitors (TKI) with little immediate progression (primary resistance). However, progression on this treatment (secondary resistance) is inevitable even for those who responded initially. These two situations are distinct in terms of management. In case of primary resistance, screening for other associated molecular abnormalities (tumour heterogeneity) should be done, even resulting in a false positive in the initial screening of EGFR mutation. In case of secondary resistance, a new pathology sample should be taken insofar as is possible to determine the presence of an acquired mutation of EGFR resistance (T790M in 60% of cases) or c-Met amplification (20% of cases). The presence of a T790M mutation could respond to irreversible EGFR-TKI, while a c-Met amplification could be managed with a targeted anti-Met therapy. However, the gold standard is still cytotoxic chemotherapy at present if a clinical trial based on a targeted therapy is not possible.
authors.affiliation: Service d'oncologie multidisciplinaire et innovations thérapeutiques & INSERM U911 CRO2, Université de la Mediterranée, Assistance publique-Hôpitaux de Marseille, hôpital Nord, Chemin des Bourrely, 13915 Marseille cedex 20, France. Fabrice.Barlesi@ap-hm.fr
authors.forename: F
authors.initials: F
authors.lastname: Barlesi
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D005784:Gene Amplification; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D011799:Quinazolines / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met; D000077156:Gefitinib