Abstract P1-08-23: Targeting Brain Metastasis: The Success of Trastuzumab-Deruxtecan in HER2+ Cancers: A Case Report

Abstract A 49-year-old female was diagnosed with invasive ductal carcinoma of the right breast in May 2021. Molecular profile of the tumor was estrogen receptor 0/8, progesterone receptor 0/8, and HER2 3+ with positive FISH, along with a TP53 mutation but without a PIK3CA mutation. Further staging with PET-CT scan showed the presence of bone lesions and extensive liver metastases, suggesting a risk of imminent liver failure. The initial treatment protocol comprised weekly paclitaxel combined with trastuzumab and pertuzumab administered every three weeks along with denosumab. There was a major response in the tumor. Paclitaxel was stopped after 18 administrations because of increasing polyneuropathy, while the administration of trastuzumab and pertuzumab continued, with prolonged disease control and excellent quality of life. In January 2024, after 25 months of confirmed response, the patient presented with symptoms of nausea, vomiting and dizziness. Neurological examination revealed a wide-based gait and was otherwise unremarkable. A CT scan of the brain identified multiple metastases with a significant mass effect, especially within the posterior fossa. This mass effect led to signs of ascending transtentorial herniation, crowding at the foramen magnum, and the secondary development of hydrocephalus. As initial treatment, high-dose corticosteroids were administered. The case was discussed at our multidisciplinary tumor board. Given the substantial burden of brain metastases, the prognosis was deemed poor. The neurosurgical team was reluctant to resect the largest brain metastasis, highlighting the potential complications and risks involved. In case of progressive hydrocephalus during the treatment course, a ventriculoperitoneal shunt was proposed as a palliative treatment to relieve intracranial pressure. Whole-brain radiation therapy was considered, however involved a substantial risk of brain herniation and significant post-treatment morbidity due to its wide-ranging impact, including potential adverse effects on healthy brain tissue. Based on the data from the Destiny Breast-01 and TUXEDO-1 trials, treatment with trastuzumab-deruxtecan monotherapy at the dose of 5.4 mg/kg was initiated. Significant clinical improvement was observed following the first treatment cycle, with sustained improvement thereafter. After three cycles, a significant radiological response was observed, with near-complete regression of the brain metastases and without signs of extra-cranial progression. At the last visit in May 2025, the patient was still in deep remission with excellent quality of life. This case illustrates that advancements in oncology and the refinement of antibody-drug conjugates are opening a new landscape of therapeutic possibilities, even in critical situations. In some cases, this progress allows the avoidance of high-risk neurosurgical procedures and reduces the morbidity associated with whole-brain radiation therapy. Initial medical approach rather than surgical or radiotherapy approach of life-threatening brain metastases should be added to the oncological armamentarium in HER2-positive breast cancer. Citation Format: Annelies Feyaerts, Yannick Van Herck, Françoise Derouane, Kristian Jochems, Thomas Decramer, Adinda Baten, Patrick Neven, Hans Wildiers. Targeting Brain Metastasis: The Success of Trastuzumab-Deruxtecan in HER2+ Cancers: A Case Report [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-08-23.