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Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2

Unlike common epidermal growth factor receptor gene (EGFR) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene (HER2) are associated with insensitivity to EGFR-TKIs, with treatment o...

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Autores principales: Takeda, Masayuki, Sakai, Kazuko, Hayashi, Hidetoshi, Tanaka, Kaoru, Tanizaki, Junko, Takahama, Takayuki, Haratani, Koji, Nishio, Kazuto, Nakagawa, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940408/
https://www.ncbi.nlm.nih.gov/pubmed/29765525
http://dx.doi.org/10.18632/oncotarget.24958
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author Takeda, Masayuki
Sakai, Kazuko
Hayashi, Hidetoshi
Tanaka, Kaoru
Tanizaki, Junko
Takahama, Takayuki
Haratani, Koji
Nishio, Kazuto
Nakagawa, Kazuhiko
author_facet Takeda, Masayuki
Sakai, Kazuko
Hayashi, Hidetoshi
Tanaka, Kaoru
Tanizaki, Junko
Takahama, Takayuki
Haratani, Koji
Nishio, Kazuto
Nakagawa, Kazuhiko
author_sort Takeda, Masayuki
collection PubMed
description Unlike common epidermal growth factor receptor gene (EGFR) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene (HER2) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel. Between July 2013 and June 2017, 206 patients with pathologically confirmed lung cancer were screened for genetic alterations including HER2 and EGFR mutations. Ten patients harbored HER2 exon-20 insertions (one of whom also carried an exon-19 deletion of EGFR), and 12 patients harbored EGFR exon-20 mutations. Five of the 13 patients with EGFR mutations were treated with EGFR-TKIs, two of whom manifested a partial response, two stable disease, and one progressive disease. Among the seven patients treated with nivolumab, one patient manifested a partial response, three stable disease, and three progressive disease, with most (86%) of these patients discontinuing treatment as a result of disease progression within 4 months. The H1047R mutation of PIK3CA detected in one patient was the only actionable mutation coexisting with the exon-20 mutations of EGFR or HER2. Potentially actionable mutations thus rarely coexist with exon-20 mutations of EGFR or HER2, and EGFR-TKIs and nivolumab show limited efficacy in patients with such exon-20 mutations.
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spelling pubmed-59404082018-05-15 Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2 Takeda, Masayuki Sakai, Kazuko Hayashi, Hidetoshi Tanaka, Kaoru Tanizaki, Junko Takahama, Takayuki Haratani, Koji Nishio, Kazuto Nakagawa, Kazuhiko Oncotarget Research Paper Unlike common epidermal growth factor receptor gene (EGFR) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene (HER2) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel. Between July 2013 and June 2017, 206 patients with pathologically confirmed lung cancer were screened for genetic alterations including HER2 and EGFR mutations. Ten patients harbored HER2 exon-20 insertions (one of whom also carried an exon-19 deletion of EGFR), and 12 patients harbored EGFR exon-20 mutations. Five of the 13 patients with EGFR mutations were treated with EGFR-TKIs, two of whom manifested a partial response, two stable disease, and one progressive disease. Among the seven patients treated with nivolumab, one patient manifested a partial response, three stable disease, and three progressive disease, with most (86%) of these patients discontinuing treatment as a result of disease progression within 4 months. The H1047R mutation of PIK3CA detected in one patient was the only actionable mutation coexisting with the exon-20 mutations of EGFR or HER2. Potentially actionable mutations thus rarely coexist with exon-20 mutations of EGFR or HER2, and EGFR-TKIs and nivolumab show limited efficacy in patients with such exon-20 mutations. Impact Journals LLC 2018-04-20 /pmc/articles/PMC5940408/ /pubmed/29765525 http://dx.doi.org/10.18632/oncotarget.24958 Text en Copyright: © 2018 Takeda et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Takeda, Masayuki
Sakai, Kazuko
Hayashi, Hidetoshi
Tanaka, Kaoru
Tanizaki, Junko
Takahama, Takayuki
Haratani, Koji
Nishio, Kazuto
Nakagawa, Kazuhiko
Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2
title Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2
title_full Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2
title_fullStr Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2
title_full_unstemmed Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2
title_short Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2
title_sort clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of egfr or her2
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940408/
https://www.ncbi.nlm.nih.gov/pubmed/29765525
http://dx.doi.org/10.18632/oncotarget.24958
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