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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

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: Cai, Boning, Li, Xiaomo, Huang, Xiang, Ma, Tonghui, Qu, Baolin, Yu, Wei, Yang, Wei, Zhang, Pei, Chen, Jing, Liu, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674488/
https://www.ncbi.nlm.nih.gov/pubmed/34926253
http://dx.doi.org/10.3389/fonc.2021.738832
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author Cai, Boning
Li, Xiaomo
Huang, Xiang
Ma, Tonghui
Qu, Baolin
Yu, Wei
Yang, Wei
Zhang, Pei
Chen, Jing
Liu, Fang
author_facet Cai, Boning
Li, Xiaomo
Huang, Xiang
Ma, Tonghui
Qu, Baolin
Yu, Wei
Yang, Wei
Zhang, Pei
Chen, Jing
Liu, Fang
author_sort Cai, Boning
collection PubMed
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.
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spelling pubmed-86744882021-12-17 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 Cai, Boning Li, Xiaomo Huang, Xiang Ma, Tonghui Qu, Baolin Yu, Wei Yang, Wei Zhang, Pei Chen, Jing Liu, Fang Front Oncol Oncology 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. Frontiers Media S.A. 2021-12-02 /pmc/articles/PMC8674488/ /pubmed/34926253 http://dx.doi.org/10.3389/fonc.2021.738832 Text en Copyright © 2021 Cai, Li, Huang, Ma, Qu, Yu, Yang, Zhang, Chen and Liu 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 Oncology
Cai, Boning
Li, Xiaomo
Huang, Xiang
Ma, Tonghui
Qu, Baolin
Yu, Wei
Yang, Wei
Zhang, Pei
Chen, Jing
Liu, Fang
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 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_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_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
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674488/
https://www.ncbi.nlm.nih.gov/pubmed/34926253
http://dx.doi.org/10.3389/fonc.2021.738832
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