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Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification

Exploring resistance mechanisms in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) upon disease progression on EGFR tyrosine kinase inhibitors (TKIs) has been an area of great interest as it may lead to effective next-line treatment strategies. Here we report a case of emergent MET ampl...

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Autores principales: Zhu, Viola W, Schrock, Alexa B, Ali, Siraj M, Ou, Sai-Hong Ignatius
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419586/
https://www.ncbi.nlm.nih.gov/pubmed/30881166
http://dx.doi.org/10.2147/LCTT.S190403
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author Zhu, Viola W
Schrock, Alexa B
Ali, Siraj M
Ou, Sai-Hong Ignatius
author_facet Zhu, Viola W
Schrock, Alexa B
Ali, Siraj M
Ou, Sai-Hong Ignatius
author_sort Zhu, Viola W
collection PubMed
description Exploring resistance mechanisms in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) upon disease progression on EGFR tyrosine kinase inhibitors (TKIs) has been an area of great interest as it may lead to effective next-line treatment strategies. Here we report a case of emergent MET amplification detected in a tumor sample from a patient with NSCLC harboring EGFR L858R mutation after disease progression on erlotinib. The patient subsequently had a sustained partial response to a combination of full-dose osimertinib and crizotinib with excellent tolerance but eventually had central nervous system (CNS) progression. Comprehensive genomic profiling performed on the resected brain sample continued to demonstrate MET amplification as an acquired resistance mechanism. A review of literature shows several groups have utilized similar combination regimens (erlotinib or osimertinib + crizotinib or cabozantinib), albeit with various dosing to target MET alterations in patients with EGFR-mutant NSCLC. As more actionable resistance mechanisms are identified, we envision combination TKI therapy will be readily adopted in clinical practice. Our case report adds to a growing body of evidence that combination osimertinib and crizotinib should be recommended to EGFR-mutant NSCLC patients with emergent MET amplification as acquired resistance. More importantly, as crizotinib has limited brain penetration, developing next-generation MET inhibitors with better CNS activity is urgently needed.
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spelling pubmed-64195862019-03-16 Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification Zhu, Viola W Schrock, Alexa B Ali, Siraj M Ou, Sai-Hong Ignatius Lung Cancer (Auckl) Case Report Exploring resistance mechanisms in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) upon disease progression on EGFR tyrosine kinase inhibitors (TKIs) has been an area of great interest as it may lead to effective next-line treatment strategies. Here we report a case of emergent MET amplification detected in a tumor sample from a patient with NSCLC harboring EGFR L858R mutation after disease progression on erlotinib. The patient subsequently had a sustained partial response to a combination of full-dose osimertinib and crizotinib with excellent tolerance but eventually had central nervous system (CNS) progression. Comprehensive genomic profiling performed on the resected brain sample continued to demonstrate MET amplification as an acquired resistance mechanism. A review of literature shows several groups have utilized similar combination regimens (erlotinib or osimertinib + crizotinib or cabozantinib), albeit with various dosing to target MET alterations in patients with EGFR-mutant NSCLC. As more actionable resistance mechanisms are identified, we envision combination TKI therapy will be readily adopted in clinical practice. Our case report adds to a growing body of evidence that combination osimertinib and crizotinib should be recommended to EGFR-mutant NSCLC patients with emergent MET amplification as acquired resistance. More importantly, as crizotinib has limited brain penetration, developing next-generation MET inhibitors with better CNS activity is urgently needed. Dove Medical Press 2019-03-12 /pmc/articles/PMC6419586/ /pubmed/30881166 http://dx.doi.org/10.2147/LCTT.S190403 Text en © 2019 Zhu et al. 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.
spellingShingle Case Report
Zhu, Viola W
Schrock, Alexa B
Ali, Siraj M
Ou, Sai-Hong Ignatius
Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification
title Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification
title_full Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification
title_fullStr Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification
title_full_unstemmed Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification
title_short Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification
title_sort differential response to a combination of full-dose osimertinib and crizotinib in a patient with egfr-mutant non-small cell lung cancer and emergent met amplification
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419586/
https://www.ncbi.nlm.nih.gov/pubmed/30881166
http://dx.doi.org/10.2147/LCTT.S190403
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