Afatinib treatment in advanced non-small cell lung cancer

Jane L Hurwitz, Paula Scullin, Lynn CampbellDepartment of Medical Oncology, Northern Ireland Cancer Centre, Belfast, UKAbstract: Despite some recent advances in the management of advanced non-small cell lung cancer (NSCLC), prognosis for these patients remains poor. Small molecule epidermal growth f...

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Autores principales:	Hurwitz JL, Scullin P, Campbell L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/741b1daef61b4425ad6261ca551bba90
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spelling	oai:doaj.org-article:741b1daef61b4425ad6261ca551bba902021-12-02T03:26:39ZAfatinib treatment in advanced non-small cell lung cancer1179-2728https://doaj.org/article/741b1daef61b4425ad6261ca551bba902011-10-01T00:00:00Zhttp://www.dovepress.com/afatinib-treatment-in-advanced-non-small-cell-lung-cancer-a8422https://doaj.org/toc/1179-2728Jane L Hurwitz, Paula Scullin, Lynn CampbellDepartment of Medical Oncology, Northern Ireland Cancer Centre, Belfast, UKAbstract: Despite some recent advances in the management of advanced non-small cell lung cancer (NSCLC), prognosis for these patients remains poor. Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have however provided a new therapeutic option in this disease setting and EGFR mutation testing is now routine practice for newly diagnosed NSCLC patients. A proportion of patients will not respond to first-generation EGFR-TKIs however, and those who do will ultimately develop resistance and disease relapse. Next-generation EGFR-TKIs which inhibit multiple members of the EGFR family are being developed in order to increase sensitivity and overcome resistance to existing agents. Afatinib (BIBW 2992) is an oral, irreversible inhibitor of EGFR and HER2 tyrosine kinases and is the most advanced of these agents in clinical development. Pre-clinical and early-phase clinical trials have demonstrated a favorable safety profile as a single agent and in combination with other anti-cancer agents, and provide evidence of clinical activity in advanced NSCLC. The LUX-Lung trials suggest that for selected patients, afatinib offers symptomatic improvement and prolonged progression-free survival, although this has not yet translated into improved overall survival. This article aims to review the use of EGFR-TKIs in the management of advanced NSCLC and the mechanisms underlying resistance to these agents. We will discuss the current pre-clinical and clinical data regarding afatinib, its potential to overcome resistance to first-generation TKIs, and its emerging role in advanced NSCLC treatment.Keywords: EGFR, tyrosine kinase inhibitor, mutation, LUX-lungHurwitz JLScullin PCampbell LDove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol 2011, Iss default, Pp 47-57 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hurwitz JL Scullin P Campbell L Afatinib treatment in advanced non-small cell lung cancer
description	Jane L Hurwitz, Paula Scullin, Lynn CampbellDepartment of Medical Oncology, Northern Ireland Cancer Centre, Belfast, UKAbstract: Despite some recent advances in the management of advanced non-small cell lung cancer (NSCLC), prognosis for these patients remains poor. Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have however provided a new therapeutic option in this disease setting and EGFR mutation testing is now routine practice for newly diagnosed NSCLC patients. A proportion of patients will not respond to first-generation EGFR-TKIs however, and those who do will ultimately develop resistance and disease relapse. Next-generation EGFR-TKIs which inhibit multiple members of the EGFR family are being developed in order to increase sensitivity and overcome resistance to existing agents. Afatinib (BIBW 2992) is an oral, irreversible inhibitor of EGFR and HER2 tyrosine kinases and is the most advanced of these agents in clinical development. Pre-clinical and early-phase clinical trials have demonstrated a favorable safety profile as a single agent and in combination with other anti-cancer agents, and provide evidence of clinical activity in advanced NSCLC. The LUX-Lung trials suggest that for selected patients, afatinib offers symptomatic improvement and prolonged progression-free survival, although this has not yet translated into improved overall survival. This article aims to review the use of EGFR-TKIs in the management of advanced NSCLC and the mechanisms underlying resistance to these agents. We will discuss the current pre-clinical and clinical data regarding afatinib, its potential to overcome resistance to first-generation TKIs, and its emerging role in advanced NSCLC treatment.Keywords: EGFR, tyrosine kinase inhibitor, mutation, LUX-lung
format	article
author	Hurwitz JL Scullin P Campbell L
author_facet	Hurwitz JL Scullin P Campbell L
author_sort	Hurwitz JL
title	Afatinib treatment in advanced non-small cell lung cancer
title_short	Afatinib treatment in advanced non-small cell lung cancer
title_full	Afatinib treatment in advanced non-small cell lung cancer
title_fullStr	Afatinib treatment in advanced non-small cell lung cancer
title_full_unstemmed	Afatinib treatment in advanced non-small cell lung cancer
title_sort	afatinib treatment in advanced non-small cell lung cancer
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/741b1daef61b4425ad6261ca551bba90
work_keys_str_mv	AT hurwitzjl afatinibtreatmentinadvancednonsmallcelllungcancer AT scullinp afatinibtreatmentinadvancednonsmallcelllungcancer AT campbelll afatinibtreatmentinadvancednonsmallcelllungcancer
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Afatinib treatment in advanced non-small cell lung cancer

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