title: [Afatinib as first-line therapy in mutation-positive EGFR. Results by type of mutation].
abstract: The discovery of endothelial growth factor receptor (EGFR) mutations has laid the foundations for personalized medicine in non-small cell lung carcinoma (NSCLC). In phase III trials, the first-generation tyrosine kinase inhibitors (TKI), gefitinib and erlotinib, demonstrated greater efficacy compared with chemotherapy in patients with EGFR mutations, achieving progression-free survival of 8-13.5 months. Afatinib, a second-generation irreversible pan-ErbB inhibitor, is the first TKI that has shown a benefit in overall survival (OS) compared with chemotherapy in EGFR mutation-positive NSCLC when used as first-line treatment. Exon 19 deletion (Del19) and the single-point substitution mutation (L858R) in exon 21, called activating mutations due to their ability to confer sensitivity to TKI, represent approximately 90% of the EGFR mutations in NSCLC. Distinct sensitivity to TKI has been observed depending on the type of mutation, with greater progression-free survival in patients with the Del19 mutation. The analysis of OS in the LUX-Lung 3 and LUX-Lung 6 trials showed a statistically significant increase in survival in afatinib-treated patients with the Del 19 mutation, but no significant increase in that of patients with the L858R mutation. Direct comparison of afatinib and gefitinib as first-line therapy (LUX-Lung 7 trial) showed a statistically-significant increase in progression-free survival (hazard ratio: 0.73; 95% confidence interval, 0.57-0.95; p=0.0165) with afatinib. In the analysis by type of mutation, this benefit was observed for both the Del19 and the L858R mutations.
authors.affiliation: Servicio de Oncología Médica, Hospital Universitari i Politècnic La Fe, Valencia, España. Electronic address: juan_osc@gva.es.
authors.forename: Óscar Juan
authors.initials: ÓJ
authors.lastname: Vidal
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D018815:Genes, erbB; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D066246:ErbB Receptors
keywords: Activating mutations; Afatinib; Cáncer de pulmón; EGFR; Inhibidores de la tirosincinasa; Lung cancer; Mutaciones activadoras; Mutaciones no comunes; Tyrosine kinase inhibitors; Uncommon mutations