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Successful Treatment of Innumerable Untreated Brain Metastases With Trastuzumab Deruxtecan in Chemotherapy-Naïve
Sara Young1, Sean C Dougherty2, Angela M DeRidder3
1Department of Internal Medicine, University of Virginia, Charlottesville, Virginia, USA.
Abstract:
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.
Insights
Trastuzumab deruxtecan shows promise for treating HER2-mutated non-small-cell lung cancer with brain metastases. This targeted therapy offers a durable response, potentially delaying whole-brain radiotherapy and its neurotoxic effects.
Area of Science:
- Oncology
- Medical Research
Background:
- Activating human epidermal growth factor receptor 2 (HER2) mutations in non-small-cell lung cancer (NSCLC) are rare but linked to brain metastases and poor prognosis.
- Trastuzumab deruxtecan (T-DXd) is an approved second-line treatment for HER2-mutated metastatic NSCLC.
Observation:
- A case study involving a patient with HER2-mutated NSCLC and brain metastases was treated with T-DXd.
- Bevacizumab was administered to manage cerebral edema, enabling corticosteroid discontinuation.
- The patient achieved significant clinical and imaging responses after two T-DXd doses, with over a year of sustained disease control.
Findings:
- T-DXd demonstrated remarkable efficacy in controlling both intracranial and systemic disease in a patient with HER2-mutated NSCLC and brain metastases.
- The treatment allowed for the deferral of whole-brain radiotherapy (WBRT), mitigating concerns about long-term neurotoxicity.
Implications:
- T-DXd may represent an effective and durable therapeutic option for NSCLC patients with brain metastases, particularly when WBRT is a consideration.
- Further clinical trials are essential to confirm the efficacy and durability of T-DXd in this patient population and to establish optimal treatment sequencing.
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