Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve HER2-Mutated Non-Small-Cell Lung Cancer

In non-small-cell lung cancer (NSCLC), activating human epidermal growth factor receptor 2 (HER2) mutations are found in a small subset of patients and are associated with a higher incidence of brain metastases (BMETSs), conferring poor survival outcomes. Trastuzumab deruxtecan (T-DXd) was recently...

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Main Authors: Sara Young, Sean C. Dougherty, Angela M. DeRidder, Camilo E. Fadul, Ryan D. Gentzler
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Case Reports in Oncological Medicine
Online Access:http://dx.doi.org/10.1155/crom/9936011
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author Sara Young
Sean C. Dougherty
Angela M. DeRidder
Camilo E. Fadul
Ryan D. Gentzler
author_facet Sara Young
Sean C. Dougherty
Angela M. DeRidder
Camilo E. Fadul
Ryan D. Gentzler
author_sort Sara Young
collection DOAJ
description In non-small-cell lung cancer (NSCLC), activating human epidermal growth factor receptor 2 (HER2) mutations are found in a small subset of patients and are associated with a higher incidence of brain metastases (BMETSs), conferring poor survival outcomes. Trastuzumab deruxtecan (T-DXd) was recently approved as a second-line agent for use in patients with previously treated, unresectable, or metastatic HER2-mutated NSCLC. We present a case of HER2-mutated NSCLC with BMETS, treated with T-DXd to defer whole-brain radiotherapy (WBRT) because of the concern of long-term neurotoxicity. He initially also received bevacizumab to address the cerebral edema, which allowed stopping corticosteroids. After the first two doses, the patient had remarkable clinical and imaging (brain and systemic) responses without progression after more than 1 year of treatment. T-DXd may be an effective and durable therapy for patients with HER2-mutated NSCLC with brain metastases in situations where intracranial disease would otherwise warrant WBRT. Clinical trials are needed to understand the efficacy and durability of T-DXd in NSCLC with BMETS and the optimal sequence of available therapies.
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spelling doaj-art-b9a71007f2de4142a72e28256cfa4c6c2025-08-20T02:19:48ZengWileyCase Reports in Oncological Medicine2090-67142025-01-01202510.1155/crom/9936011Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve HER2-Mutated Non-Small-Cell Lung CancerSara Young0Sean C. Dougherty1Angela M. DeRidder2Camilo E. Fadul3Ryan D. Gentzler4Department of Internal MedicineDivision of Hematology/OncologyDepartment of Hematology/OncologyDivision of Neuro-OncologyDivision of Hematology/OncologyIn non-small-cell lung cancer (NSCLC), activating human epidermal growth factor receptor 2 (HER2) mutations are found in a small subset of patients and are associated with a higher incidence of brain metastases (BMETSs), conferring poor survival outcomes. Trastuzumab deruxtecan (T-DXd) was recently approved as a second-line agent for use in patients with previously treated, unresectable, or metastatic HER2-mutated NSCLC. We present a case of HER2-mutated NSCLC with BMETS, treated with T-DXd to defer whole-brain radiotherapy (WBRT) because of the concern of long-term neurotoxicity. He initially also received bevacizumab to address the cerebral edema, which allowed stopping corticosteroids. After the first two doses, the patient had remarkable clinical and imaging (brain and systemic) responses without progression after more than 1 year of treatment. T-DXd may be an effective and durable therapy for patients with HER2-mutated NSCLC with brain metastases in situations where intracranial disease would otherwise warrant WBRT. Clinical trials are needed to understand the efficacy and durability of T-DXd in NSCLC with BMETS and the optimal sequence of available therapies.http://dx.doi.org/10.1155/crom/9936011
spellingShingle Sara Young
Sean C. Dougherty
Angela M. DeRidder
Camilo E. Fadul
Ryan D. Gentzler
Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve HER2-Mutated Non-Small-Cell Lung Cancer
Case Reports in Oncological Medicine
title Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve HER2-Mutated Non-Small-Cell Lung Cancer
title_full Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve HER2-Mutated Non-Small-Cell Lung Cancer
title_fullStr Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve HER2-Mutated Non-Small-Cell Lung Cancer
title_full_unstemmed Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve HER2-Mutated Non-Small-Cell Lung Cancer
title_short Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve HER2-Mutated Non-Small-Cell Lung Cancer
title_sort successful treatment of innumerable untreated brain metastases with trastuzumab deruxtecan in chemotherapy naive her2 mutated non small cell lung cancer
url http://dx.doi.org/10.1155/crom/9936011
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