NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report

IntroductionA 73-year-old Chinese woman with no smoking history was diagnosed with stage IV adenocarcinoma of the lung in August 2020, presenting with left chest pain and multiple lung lesions.Patient concernsThe patient experienced chest pain for 2 months before diagnosis. Initial CT scans revealed...

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Main Authors: Jielin Li, Yunyun Shi, Mengge Zheng, Chenkang Yang, Hong Gao, Xiaoling Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1571777/full
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author Jielin Li
Yunyun Shi
Mengge Zheng
Chenkang Yang
Hong Gao
Xiaoling Li
author_facet Jielin Li
Yunyun Shi
Mengge Zheng
Chenkang Yang
Hong Gao
Xiaoling Li
author_sort Jielin Li
collection DOAJ
description IntroductionA 73-year-old Chinese woman with no smoking history was diagnosed with stage IV adenocarcinoma of the lung in August 2020, presenting with left chest pain and multiple lung lesions.Patient concernsThe patient experienced chest pain for 2 months before diagnosis. Initial CT scans revealed multiple lung nodules, enlarged lymph nodes, and pleural effusion.DiagnosisThe diagnosis was confirmed as advanced NSCLC the left upper lobe of the lung with specific genetic alterations, including EGFR 19del, EGFR amplification, and TPR-NTRK1 fusion, through molecular testing.InterventionsPrior treatments included the first-line therapy gefitinib (250 mg/day) administered from September 2020 to June 2021, targeting the EGFR 19del mutation, achieving a partial response (PR). The second-line therapy osimertinib (80 mg/day) was administered from July 2021 to January 2022, targeting EGFR 19del and T790M mutations, with a progression-free survival (PFS) of approximately 7 months. The third-line therapy almonertinib, another third-generation EGFR-TKI, was administered from January 2022 to March 2022, but the response was poor, leading to further progression. After identifying NTRK fusion and EGFR amplification, the patient was administered larotrectinib as third-line treatment. Prior treatments included targeted therapies and chemotherapy.OutcomesDespite multiple lines of targeted therapy, the patient experienced rapid disease progression at several points, highlighting the challenges in managing NSCLC with complex genetic alterations.ConclusionThis case underscores the importance of ongoing molecular testing and the potential need for combination therapies in managing advanced NSCLC with resistance to multiple targeted treatments. The current treatment with camrelizumab combined with chemotherapy shows promise, but further monitoring is necessary.
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spelling doaj-art-2be8c4e4ec864e3bb23e77b1b68f0c132025-08-20T03:44:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.15717771571777NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case reportJielin Li0Yunyun Shi1Mengge Zheng2Chenkang Yang3Hong Gao4Xiaoling Li5Department of Thoracic Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, ChinaGenetron Health (Beijing) Co. Ltd., Beijing, ChinaGenetron Health (Beijing) Co. Ltd., Beijing, ChinaGenetron Health (Beijing) Co. Ltd., Beijing, ChinaDepartment of Thoracic Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, ChinaDepartment of Thoracic Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, ChinaIntroductionA 73-year-old Chinese woman with no smoking history was diagnosed with stage IV adenocarcinoma of the lung in August 2020, presenting with left chest pain and multiple lung lesions.Patient concernsThe patient experienced chest pain for 2 months before diagnosis. Initial CT scans revealed multiple lung nodules, enlarged lymph nodes, and pleural effusion.DiagnosisThe diagnosis was confirmed as advanced NSCLC the left upper lobe of the lung with specific genetic alterations, including EGFR 19del, EGFR amplification, and TPR-NTRK1 fusion, through molecular testing.InterventionsPrior treatments included the first-line therapy gefitinib (250 mg/day) administered from September 2020 to June 2021, targeting the EGFR 19del mutation, achieving a partial response (PR). The second-line therapy osimertinib (80 mg/day) was administered from July 2021 to January 2022, targeting EGFR 19del and T790M mutations, with a progression-free survival (PFS) of approximately 7 months. The third-line therapy almonertinib, another third-generation EGFR-TKI, was administered from January 2022 to March 2022, but the response was poor, leading to further progression. After identifying NTRK fusion and EGFR amplification, the patient was administered larotrectinib as third-line treatment. Prior treatments included targeted therapies and chemotherapy.OutcomesDespite multiple lines of targeted therapy, the patient experienced rapid disease progression at several points, highlighting the challenges in managing NSCLC with complex genetic alterations.ConclusionThis case underscores the importance of ongoing molecular testing and the potential need for combination therapies in managing advanced NSCLC with resistance to multiple targeted treatments. The current treatment with camrelizumab combined with chemotherapy shows promise, but further monitoring is necessary.https://www.frontiersin.org/articles/10.3389/fphar.2025.1571777/fullEGFR-mutated NSCLCNTRK-fusionlarotrectinibresistancecase report
spellingShingle Jielin Li
Yunyun Shi
Mengge Zheng
Chenkang Yang
Hong Gao
Xiaoling Li
NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report
Frontiers in Pharmacology
EGFR-mutated NSCLC
NTRK-fusion
larotrectinib
resistance
case report
title NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report
title_full NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report
title_fullStr NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report
title_full_unstemmed NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report
title_short NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report
title_sort ntrk1 fusion as an acquired resistance mechanism in egfrex19 mutated nsclc a case report
topic EGFR-mutated NSCLC
NTRK-fusion
larotrectinib
resistance
case report
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1571777/full
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