Presence of MET exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an EGFR exon 19 deletion that responds to combination of capmatinib and osimertinb: A case report

Lung cancer stands as a leading cause of mortality in China, with EGFR mutations frequently identified as pivotal driver genes. Osimertinib, a tyrosine kinase inhibitor targeting EGFR mutations, is typically employed as a first-line treatment for EGFR-sensitive mutations; nevertheless, resistance ca...

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Main Authors: Siqi Xiang, Liang Zeng, Mingjun Xiang, Yongchang Zhang
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023097232
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author Siqi Xiang
Liang Zeng
Mingjun Xiang
Yongchang Zhang
author_facet Siqi Xiang
Liang Zeng
Mingjun Xiang
Yongchang Zhang
author_sort Siqi Xiang
collection DOAJ
description Lung cancer stands as a leading cause of mortality in China, with EGFR mutations frequently identified as pivotal driver genes. Osimertinib, a tyrosine kinase inhibitor targeting EGFR mutations, is typically employed as a first-line treatment for EGFR-sensitive mutations; nevertheless, resistance can emerge. In this case report, we present the case of a 53-year-old non-smoking male diagnosed with stage IV lung adenocarcinoma bearing an EGFR exon 19 deletion. This patient eventually developed resistance to both Erlotinib and Osimertinib after 28 months of treatment. Subsequent genetic testing uncovered the emergence of new MET exon 14 skipping and MET fusion, coexisting with the initial EGFR exon 19 deletion. In light of this complex molecular profile, the patient was administered a combination therapy consisting of Osimertinib and Capmatinib. This novel approach yielded a partial response, and notably, the patient experienced a progression-free survival exceeding 7 months. Vigilant monitoring of the patient's progress revealed the disappearance of the MET exon 14 skipping and a notable improvement in the patient's symptoms. This case report underscores the potential efficacy of Osimertinib and Capmatinib combination therapy as a viable treatment strategy for patients harboring EGFR-mutated lung cancer who develop resistance to first-line EGFR inhibitors due to MET activation.
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spelling doaj.art-d031b2eaa3d244ce94ceeb5d6b22e8852023-12-02T07:06:04ZengElsevierHeliyon2405-84402023-11-01911e22515Presence of MET exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an EGFR exon 19 deletion that responds to combination of capmatinib and osimertinb: A case reportSiqi Xiang0Liang Zeng1Mingjun Xiang2Yongchang Zhang3Department of Biochemistry and Immunology, Medical Research Center, Institute of Medicine, Jishou University, Jishou, 416000, China; Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, ChinaDepartment of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, ChinaDepartment of Biochemistry and Immunology, Medical Research Center, Institute of Medicine, Jishou University, Jishou, 416000, ChinaDepartment of Biochemistry and Immunology, Medical Research Center, Institute of Medicine, Jishou University, Jishou, 416000, China; Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China; Corresponding author. Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University; Changsha, 410013, China.Lung cancer stands as a leading cause of mortality in China, with EGFR mutations frequently identified as pivotal driver genes. Osimertinib, a tyrosine kinase inhibitor targeting EGFR mutations, is typically employed as a first-line treatment for EGFR-sensitive mutations; nevertheless, resistance can emerge. In this case report, we present the case of a 53-year-old non-smoking male diagnosed with stage IV lung adenocarcinoma bearing an EGFR exon 19 deletion. This patient eventually developed resistance to both Erlotinib and Osimertinib after 28 months of treatment. Subsequent genetic testing uncovered the emergence of new MET exon 14 skipping and MET fusion, coexisting with the initial EGFR exon 19 deletion. In light of this complex molecular profile, the patient was administered a combination therapy consisting of Osimertinib and Capmatinib. This novel approach yielded a partial response, and notably, the patient experienced a progression-free survival exceeding 7 months. Vigilant monitoring of the patient's progress revealed the disappearance of the MET exon 14 skipping and a notable improvement in the patient's symptoms. This case report underscores the potential efficacy of Osimertinib and Capmatinib combination therapy as a viable treatment strategy for patients harboring EGFR-mutated lung cancer who develop resistance to first-line EGFR inhibitors due to MET activation.http://www.sciencedirect.com/science/article/pii/S2405844023097232MET exon 14 skippingMET fusionResistance mechanismOsimertinibCapmatinibEGFR
spellingShingle Siqi Xiang
Liang Zeng
Mingjun Xiang
Yongchang Zhang
Presence of MET exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an EGFR exon 19 deletion that responds to combination of capmatinib and osimertinb: A case report
Heliyon
MET exon 14 skipping
MET fusion
Resistance mechanism
Osimertinib
Capmatinib
EGFR
title Presence of MET exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an EGFR exon 19 deletion that responds to combination of capmatinib and osimertinb: A case report
title_full Presence of MET exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an EGFR exon 19 deletion that responds to combination of capmatinib and osimertinb: A case report
title_fullStr Presence of MET exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an EGFR exon 19 deletion that responds to combination of capmatinib and osimertinb: A case report
title_full_unstemmed Presence of MET exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an EGFR exon 19 deletion that responds to combination of capmatinib and osimertinb: A case report
title_short Presence of MET exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an EGFR exon 19 deletion that responds to combination of capmatinib and osimertinb: A case report
title_sort presence of met exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an egfr exon 19 deletion that responds to combination of capmatinib and osimertinb a case report
topic MET exon 14 skipping
MET fusion
Resistance mechanism
Osimertinib
Capmatinib
EGFR
url http://www.sciencedirect.com/science/article/pii/S2405844023097232
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