Cargando…
Afatinib for the treatment of metastatic non-small cell lung cancer
Targeting the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC) harboring sensitizing mutations in the tyrosine kinase (TKI) domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340466/ https://www.ncbi.nlm.nih.gov/pubmed/25733926 http://dx.doi.org/10.2147/CMAR.S51808 |
_version_ | 1782359028644446208 |
---|---|
author | Joshi, Monika Rizvi, Syed M Belani, Chandra P |
author_facet | Joshi, Monika Rizvi, Syed M Belani, Chandra P |
author_sort | Joshi, Monika |
collection | PubMed |
description | Targeting the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC) harboring sensitizing mutations in the tyrosine kinase (TKI) domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in exon 18, in-frame deletions or insertion of exon 19, L858R or L861Q mutation in exon 21. Approximately 90% of these mutations are exon 19 deletion or exon 21 L858R point mutation. Gefitinib and erlotinib are reversible first-generation inhibitors of mutant EGFR, and treatment with these agents in the first-line setting has demonstrated a progression-free survival of 9.5–13.7 months. However, the majority of these patients ultimately develop resistance to these drugs. Afatinib is an irreversible pan-ErbB inhibitor that was developed to circumvent the problem of resistance to first-generation TKIs. The LUX-Lung studies have evaluated the efficacy and toxicities of afatinib in treatment-naïve and refractory NSCLC patients. The promising results of some of these trials led to approval of afatinib by the US Food and Drug Administration for patients with advanced NSCLC and EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. Afatinib causes toxicities similar to those of the first-generation EGFR TKIs, such as diarrhea, rash, acne, and stomatitis, and overall is well tolerated. This article focuses on the clinical studies of afatinib in patients with NSCLC. |
format | Online Article Text |
id | pubmed-4340466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43404662015-03-02 Afatinib for the treatment of metastatic non-small cell lung cancer Joshi, Monika Rizvi, Syed M Belani, Chandra P Cancer Manag Res Review Targeting the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC) harboring sensitizing mutations in the tyrosine kinase (TKI) domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in exon 18, in-frame deletions or insertion of exon 19, L858R or L861Q mutation in exon 21. Approximately 90% of these mutations are exon 19 deletion or exon 21 L858R point mutation. Gefitinib and erlotinib are reversible first-generation inhibitors of mutant EGFR, and treatment with these agents in the first-line setting has demonstrated a progression-free survival of 9.5–13.7 months. However, the majority of these patients ultimately develop resistance to these drugs. Afatinib is an irreversible pan-ErbB inhibitor that was developed to circumvent the problem of resistance to first-generation TKIs. The LUX-Lung studies have evaluated the efficacy and toxicities of afatinib in treatment-naïve and refractory NSCLC patients. The promising results of some of these trials led to approval of afatinib by the US Food and Drug Administration for patients with advanced NSCLC and EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. Afatinib causes toxicities similar to those of the first-generation EGFR TKIs, such as diarrhea, rash, acne, and stomatitis, and overall is well tolerated. This article focuses on the clinical studies of afatinib in patients with NSCLC. Dove Medical Press 2015-02-19 /pmc/articles/PMC4340466/ /pubmed/25733926 http://dx.doi.org/10.2147/CMAR.S51808 Text en © 2015 Joshi et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Review Joshi, Monika Rizvi, Syed M Belani, Chandra P Afatinib for the treatment of metastatic non-small cell lung cancer |
title | Afatinib for the treatment of metastatic non-small cell lung cancer |
title_full | Afatinib for the treatment of metastatic non-small cell lung cancer |
title_fullStr | Afatinib for the treatment of metastatic non-small cell lung cancer |
title_full_unstemmed | Afatinib for the treatment of metastatic non-small cell lung cancer |
title_short | Afatinib for the treatment of metastatic non-small cell lung cancer |
title_sort | afatinib for the treatment of metastatic non-small cell lung cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340466/ https://www.ncbi.nlm.nih.gov/pubmed/25733926 http://dx.doi.org/10.2147/CMAR.S51808 |
work_keys_str_mv | AT joshimonika afatinibforthetreatmentofmetastaticnonsmallcelllungcancer AT rizvisyedm afatinibforthetreatmentofmetastaticnonsmallcelllungcancer AT belanichandrap afatinibforthetreatmentofmetastaticnonsmallcelllungcancer |