[Afatinib as first-line therapy in mutation-positive EGFR. Results by type of mutation].
| Autor: | Vidal ÓJ; Servicio de Oncología Médica, Hospital Universitari i Politècnic La Fe, Valencia, España. Electronic address: juan_osc@gva.es. |
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| Jazyk: | Spanish; Castilian |
| Zdroj: | Medicina clinica [Med Clin (Barc)] 2016 Apr; Vol. 146 Suppl 1, pp. 12-8. |
| DOI: | 10.1016/S0025-7753(16)30258-5 |
| Abstrakt: | 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. (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.) |
| Databáze: | MEDLINE |
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