Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for advanced non-small-cell lung cancer (NSCLC) patients. However, most patients will eventually develop resistance. For EGFR-TKI resistance mediated by MET amplification, the combination of EGFR and M...

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Autores principales:	Boning Cai, Xiaomo Li, Xiang Huang, Tonghui Ma, Baolin Qu, Wei Yu, Wei Yang, Pei Zhang, Jing Chen, Fang Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	non-small cell lung cancer (NSCLC) EGFR mutation targeted therapy resistance MET amplification case report Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0fb222ca7ab849f6a9487d56a8f4dbdc
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spelling	oai:doaj.org-article:0fb222ca7ab849f6a9487d56a8f4dbdc2021-12-02T08:22:34ZCase Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation2234-943X10.3389/fonc.2021.738832https://doaj.org/article/0fb222ca7ab849f6a9487d56a8f4dbdc2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.738832/fullhttps://doaj.org/toc/2234-943XEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for advanced non-small-cell lung cancer (NSCLC) patients. However, most patients will eventually develop resistance. For EGFR-TKI resistance mediated by MET amplification, the combination of EGFR and MET TKIs has shown promising results in early clinical trials. However, acquired resistance to MET inhibitors forms a formidable challenge to this dual blockade approach. Here, we presented an NSCLC patient with EGFR exon 19 deletion (ex19del) who was resistant to first-line erlotinib treatment but responded to chemotherapy. Given the finding of MET overexpression/amplification after disease progression, the patient received gefitinib plus crizotinib with a partial response. Her disease progressed again, and molecular testing revealed a novel MET Y1230H mutation and a PD-L1 TPS score of 75%. She received a salvage regime consisting of gefitinib, cabozantinib, and pembrolizumab with a partial response. Since we now know that EGFR ex19del NSCLC patients generally do not respond to PD-1 blockade therapy, this response is more likely the contribution from gefitinib plus cabozantinib. Therefore, sequential use of type I and II MET inhibitors in EGFR/MET dual blockade may be an effective therapeutic option for EGFR-mutant, MET-amplified NSCLC.Boning CaiXiaomo LiXiang HuangTonghui MaBaolin QuWei YuWei YangPei ZhangJing ChenFang LiuFrontiers Media S.A.articlenon-small cell lung cancer (NSCLC)EGFR mutationtargeted therapy resistanceMET amplificationcase reportNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	non-small cell lung cancer (NSCLC) EGFR mutation targeted therapy resistance MET amplification case report Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	non-small cell lung cancer (NSCLC) EGFR mutation targeted therapy resistance MET amplification case report Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Boning Cai Xiaomo Li Xiang Huang Tonghui Ma Baolin Qu Wei Yu Wei Yang Pei Zhang Jing Chen Fang Liu Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation
description	Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for advanced non-small-cell lung cancer (NSCLC) patients. However, most patients will eventually develop resistance. For EGFR-TKI resistance mediated by MET amplification, the combination of EGFR and MET TKIs has shown promising results in early clinical trials. However, acquired resistance to MET inhibitors forms a formidable challenge to this dual blockade approach. Here, we presented an NSCLC patient with EGFR exon 19 deletion (ex19del) who was resistant to first-line erlotinib treatment but responded to chemotherapy. Given the finding of MET overexpression/amplification after disease progression, the patient received gefitinib plus crizotinib with a partial response. Her disease progressed again, and molecular testing revealed a novel MET Y1230H mutation and a PD-L1 TPS score of 75%. She received a salvage regime consisting of gefitinib, cabozantinib, and pembrolizumab with a partial response. Since we now know that EGFR ex19del NSCLC patients generally do not respond to PD-1 blockade therapy, this response is more likely the contribution from gefitinib plus cabozantinib. Therefore, sequential use of type I and II MET inhibitors in EGFR/MET dual blockade may be an effective therapeutic option for EGFR-mutant, MET-amplified NSCLC.
format	article
author	Boning Cai Xiaomo Li Xiang Huang Tonghui Ma Baolin Qu Wei Yu Wei Yang Pei Zhang Jing Chen Fang Liu
author_facet	Boning Cai Xiaomo Li Xiang Huang Tonghui Ma Baolin Qu Wei Yu Wei Yang Pei Zhang Jing Chen Fang Liu
author_sort	Boning Cai
title	Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation
title_short	Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation
title_full	Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation
title_fullStr	Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation
title_full_unstemmed	Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation
title_sort	case report: sequential combination targeted therapy with type i and ii met inhibitors in a metastatic egfr-mutated, met-amplified nsclc patient with acquired met y1230h mutation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0fb222ca7ab849f6a9487d56a8f4dbdc
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Case Report: Sequential Combination Targeted Therapy With Type I and II MET Inhibitors in a Metastatic EGFR-Mutated, MET-Amplified NSCLC Patient With Acquired MET Y1230H Mutation

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