Intracranial activity of T-DXd in HER2+ Metastatic Breast Cancer

Dr Annelies Feyaerts is a medical oncology resident at the University Hospitals Leuven. During SABCS 2024 she presented a clinical case illustrating the intracranial activity of trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer. The poster describes a 49-year-old woman who was diagnosed with a HER2-positive, HR-negative invasive ductal carcinoma of the right breast in May 2021. 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 tumour. Paclitaxel was stopped after 18 administrations because of increasing polyneuropathy, while the administration of trastuzumab and pertuzumab continued, with prolonged disease control and an excellent quality of life. However, in January 2024, the patient presented with symptoms of nausea, vomiting and dizziness. A CT scan of the brain identified multiple metastases with a significant mass in the posterior fossa. The neurosurgical team was reluctant to resect the largest brain metastasis. Whole-brain radiation therapy was considered, but this involved a substantial risk of brain herniation and significant post-treatment morbidity. Based on the data from the Destiny Breast-01 and TUXEDO-1 trials, a treatment with trastuzumab-deruxtecan (T-DXd) at the dose of 5.4 mg/kg was therefore initiated. A significant clinical improvement was observed following the first treatment cycle, with a 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 an excellent quality of life.