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Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports

The acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable and heterogeneous. The strategies to overcome acquired resistance are significant. For patients with secondary T790M-positive after early generation EGFR-TKIs, osimertinib is the standard...

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Autores principales: Zeng, Yue, Feng, Yuanqing, Fu, Guihua, Jiang, Junlan, Liu, Xiaohan, Pan, Yue, Hu, Chunhong, Liu, Xianling, Wu, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020767/
https://www.ncbi.nlm.nih.gov/pubmed/35462930
http://dx.doi.org/10.3389/fphar.2022.838247
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author Zeng, Yue
Feng, Yuanqing
Fu, Guihua
Jiang, Junlan
Liu, Xiaohan
Pan, Yue
Hu, Chunhong
Liu, Xianling
Wu, Fang
author_facet Zeng, Yue
Feng, Yuanqing
Fu, Guihua
Jiang, Junlan
Liu, Xiaohan
Pan, Yue
Hu, Chunhong
Liu, Xianling
Wu, Fang
author_sort Zeng, Yue
collection PubMed
description The acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable and heterogeneous. The strategies to overcome acquired resistance are significant. For patients with secondary T790M-positive after early generation EGFR-TKIs, osimertinib is the standard second-line therapy. In patients resistant to prior early generation EGFR-TKIs, the acquired T790M mutation overlaps with other driver gene resistance, such as HER2-and MET amplification, accounting for 4–8%. The efficacy of osimertinib is unclear in patients with concurrent multiple driver gene resistance. We here report a patient who acquired EGFR T790M, STRN-ALK fusion, and EGFR amplification after gefitinib progression and subsequent MET amplification acquired from osimertinib. The other patient acquired EGFR T790M and MET amplification post-dacomitinib and acquired CCDC6-RET fusion after osimertinib treatment. Besides, subsequent new bypass activations were the possible resistance mechanisms to second-line osimertinib. Both patients had progression-free survival (PFS) less than 4 months and limited benefits from osimertinib second-line therapy. The T790M accompanying driver gene resistance will be a new subtype after EGFR-TKIs progression, needing effective treatment options.
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spelling pubmed-90207672022-04-21 Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports Zeng, Yue Feng, Yuanqing Fu, Guihua Jiang, Junlan Liu, Xiaohan Pan, Yue Hu, Chunhong Liu, Xianling Wu, Fang Front Pharmacol Pharmacology The acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable and heterogeneous. The strategies to overcome acquired resistance are significant. For patients with secondary T790M-positive after early generation EGFR-TKIs, osimertinib is the standard second-line therapy. In patients resistant to prior early generation EGFR-TKIs, the acquired T790M mutation overlaps with other driver gene resistance, such as HER2-and MET amplification, accounting for 4–8%. The efficacy of osimertinib is unclear in patients with concurrent multiple driver gene resistance. We here report a patient who acquired EGFR T790M, STRN-ALK fusion, and EGFR amplification after gefitinib progression and subsequent MET amplification acquired from osimertinib. The other patient acquired EGFR T790M and MET amplification post-dacomitinib and acquired CCDC6-RET fusion after osimertinib treatment. Besides, subsequent new bypass activations were the possible resistance mechanisms to second-line osimertinib. Both patients had progression-free survival (PFS) less than 4 months and limited benefits from osimertinib second-line therapy. The T790M accompanying driver gene resistance will be a new subtype after EGFR-TKIs progression, needing effective treatment options. Frontiers Media S.A. 2022-04-06 /pmc/articles/PMC9020767/ /pubmed/35462930 http://dx.doi.org/10.3389/fphar.2022.838247 Text en Copyright © 2022 Zeng, Feng, Fu, Jiang, Liu, Pan, Hu, Liu and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zeng, Yue
Feng, Yuanqing
Fu, Guihua
Jiang, Junlan
Liu, Xiaohan
Pan, Yue
Hu, Chunhong
Liu, Xianling
Wu, Fang
Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports
title Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports
title_full Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports
title_fullStr Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports
title_full_unstemmed Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports
title_short Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports
title_sort acquired concurrent egfr t790m and driver gene resistance from egfr-tkis hampered osimertinib efficacy in advanced lung adenocarcinoma: case reports
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020767/
https://www.ncbi.nlm.nih.gov/pubmed/35462930
http://dx.doi.org/10.3389/fphar.2022.838247
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