An antibody-drug conjugate, trastuzumab deruxtecan (T-DXd), has demonstrated promising activity against HER2-positive breast cancer that has spread to the brain. The findings from the DESTINY-Breast 12 trial, presented at the European Society of Medical Oncology Congress, suggest that T-DXd could offer a substantial benefit for patients with this challenging condition. The study, led by researchers at the Dana-Farber Cancer Institute, highlights the potential of targeted therapies to overcome the limitations of conventional treatments for brain metastases.
DESTINY-Breast 12 Trial Results
The DESTINY-Breast 12 trial enrolled 504 patients with HER2-positive breast cancer across 78 centers in Western Europe, Japan, Australia, and the U.S. Among these patients, 263 had active or stable brain metastases, while 241 had no brain metastases. All participants had previously received at least one line of therapy.
After a median follow-up of 15.4 months, the median progression-free survival (PFS) in patients with brain metastases was 17.3 months. The 12-month PFS rate was 61.6%. Furthermore, 71% of participants experienced an intracranial objective response, indicating a measurable reduction in cancer within the central nervous system.
Impact on Survival and Overall Response
The study also revealed a high level of response in tumors outside the central nervous system, regardless of the presence of brain metastases. Approximately 90% of patients in both groups were alive one year after initiating treatment with T-DXd.
Nancy Lin, MD, leader of the trial and senior author of the study published in Nature Medicine, noted the significance of these findings. "Our data show that T-DXd has substantial and durable activity within the brain in patients with HER2-positive breast cancer that has metastasized there," she stated.
Safety and Tolerability
The side effects associated with T-DXd were consistent with those reported in previous studies, including nausea, constipation, neutropenia, fatigue, and anemia. Interstitial lung disease, a known potential side effect of T-DXd, was observed at levels comparable to prior research, underscoring the importance of monitoring patients for its development.
Mechanism of Action
T-DXd comprises the chemotherapy agent deruxtecan linked to trastuzumab, a monoclonal antibody that targets the HER2 protein on breast cancer cells. This targeted approach allows for the direct delivery of chemotherapy to the tumor site, potentially minimizing systemic toxicity and enhancing efficacy, especially in hard-to-treat areas like the brain.
Clinical Context and Current Treatment Landscape
Brain metastases occur in as many as half of patients with HER2-positive breast cancer and are associated with a poorer prognosis compared to breast cancer that has not spread to the brain. Current treatments for brain metastases typically involve localized therapies such as surgery, radiosurgery, and radiation therapy. However, these treatments often provide only temporary relief, with disease progression in the central nervous system occurring within six to 12 months.
The encouraging results from the DESTINY-Breast 12 trial suggest that T-DXd could represent a valuable new option for patients with HER2-positive breast cancer brain metastases, addressing a critical unmet need in this population.
