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Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study
Purpose: A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimer...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549661/ https://www.ncbi.nlm.nih.gov/pubmed/31213907 http://dx.doi.org/10.2147/CMAR.S207170 |
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author | Igawa, Satoshi Ono, Taihei Kasajima, Masashi Ishihara, Mikiko Hiyoshi, Yasuhiro Kusuhara, Seiichiro Nishinarita, Noriko Fukui, Tomoya Kubota, Masaru Sasaki, Jiichiro Hisashi, Mitsufuji Yokoba, Masanori Katagiri, Masato Naoki, Katsuhiko |
author_facet | Igawa, Satoshi Ono, Taihei Kasajima, Masashi Ishihara, Mikiko Hiyoshi, Yasuhiro Kusuhara, Seiichiro Nishinarita, Noriko Fukui, Tomoya Kubota, Masaru Sasaki, Jiichiro Hisashi, Mitsufuji Yokoba, Masanori Katagiri, Masato Naoki, Katsuhiko |
author_sort | Igawa, Satoshi |
collection | PubMed |
description | Purpose: A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating EGFR mutation, ie, exon 19 deletion or L858R point mutation. Patients and methods: A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation. Results: A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (P=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS. Conclusion: Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib. |
format | Online Article Text |
id | pubmed-6549661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-65496612019-06-18 Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study Igawa, Satoshi Ono, Taihei Kasajima, Masashi Ishihara, Mikiko Hiyoshi, Yasuhiro Kusuhara, Seiichiro Nishinarita, Noriko Fukui, Tomoya Kubota, Masaru Sasaki, Jiichiro Hisashi, Mitsufuji Yokoba, Masanori Katagiri, Masato Naoki, Katsuhiko Cancer Manag Res Original Research Purpose: A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating EGFR mutation, ie, exon 19 deletion or L858R point mutation. Patients and methods: A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation. Results: A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (P=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS. Conclusion: Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib. Dove 2019-05-28 /pmc/articles/PMC6549661/ /pubmed/31213907 http://dx.doi.org/10.2147/CMAR.S207170 Text en © 2019 Igawa et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Igawa, Satoshi Ono, Taihei Kasajima, Masashi Ishihara, Mikiko Hiyoshi, Yasuhiro Kusuhara, Seiichiro Nishinarita, Noriko Fukui, Tomoya Kubota, Masaru Sasaki, Jiichiro Hisashi, Mitsufuji Yokoba, Masanori Katagiri, Masato Naoki, Katsuhiko Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study |
title | Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study |
title_full | Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study |
title_fullStr | Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study |
title_full_unstemmed | Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study |
title_short | Impact of EGFR genotype on the efficacy of osimertinib in EGFR tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study |
title_sort | impact of egfr genotype on the efficacy of osimertinib in egfr tyrosine kinase inhibitor-resistant patients with non-small cell lung cancer: a prospective observational study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549661/ https://www.ncbi.nlm.nih.gov/pubmed/31213907 http://dx.doi.org/10.2147/CMAR.S207170 |
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