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

Viola W Zhu,1 Alexa B Schrock,2 Siraj M Ali,2 Sai-Hong Ignatius Ou1 1Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine School of Medicine, Orange, CA, USA; 2Clinical Development, Foundation Medicine, Inc., Cambridge, MA...

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Autores principales:	Zhu VW, Schrock AB, Ali SM, Ou SI
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	osimertinib crizotinib EGFR MET amplification erlotinib (3-6) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/92497f75a8b94fb7b5a39d98c3997684
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spelling	oai:doaj.org-article:92497f75a8b94fb7b5a39d98c39976842021-12-02T04:27:18ZDifferential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification1179-2728https://doaj.org/article/92497f75a8b94fb7b5a39d98c39976842019-03-01T00:00:00Zhttps://www.dovepress.com/differential-response-to-a-combination-of-full-dose-osimertinib-and-cr-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Viola W Zhu,1 Alexa B Schrock,2 Siraj M Ali,2 Sai-Hong Ignatius Ou1 1Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine School of Medicine, Orange, CA, USA; 2Clinical Development, Foundation Medicine, Inc., Cambridge, MA, USA Abstract: 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. Keywords: resistance, TKI, erlotinib, cabozantinib, CGP, gefitinibZhu VWSchrock ABAli SMOu SIDove Medical PressarticleosimertinibcrizotinibEGFRMETamplificationerlotinib (3-6)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 10, Pp 21-26 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	osimertinib crizotinib EGFR MET amplification erlotinib (3-6) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	osimertinib crizotinib EGFR MET amplification erlotinib (3-6) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Zhu VW Schrock AB Ali SM Ou SI 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
description	Viola W Zhu,1 Alexa B Schrock,2 Siraj M Ali,2 Sai-Hong Ignatius Ou1 1Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine School of Medicine, Orange, CA, USA; 2Clinical Development, Foundation Medicine, Inc., Cambridge, MA, USA Abstract: 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. Keywords: resistance, TKI, erlotinib, cabozantinib, CGP, gefitinib
format	article
author	Zhu VW Schrock AB Ali SM Ou SI
author_facet	Zhu VW Schrock AB Ali SM Ou SI
author_sort	Zhu VW
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_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_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_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
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/92497f75a8b94fb7b5a39d98c3997684
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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

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