New Study Shows Tucatinib Delays Progression in Breast Cancer Spread to Brain
Trial Results ESMO Madrid
A national clinical trial led by Duke University School of Medicine found that adding tucatinib to standard care substantially delayed worsening in HER2-positive breast cancer patients with new brain metastases. The results were presented on October 26, 2026, at the European Society for Medical Oncology Congress in Madrid, Spain. Senior author Carey K. Anders, MD, professor of medicine at Duke and a member of the Duke Cancer Institute, and Sarah L. Sammons, an associate professor at the University of Maryland Greenebaum Cancer Center, presented the data on behalf of the Hoosier Cancer Research Network.
Crossing the Blood-Brain Barrier
Tucatinib is already FDA approved for use in patients with advanced or metastatic HER2-positive breast cancer. An advantage of the drug is that it crosses the blood-brain barrier, which means it can reach cancer cells in the brain. The phase 2 BRIDGET trial tested adding tucatinib earlier in patients who had recently experienced a first or second brain metastasis while the cancer outside the brain remained under control. After treatment of brain lesions with radiosurgery, patients received tucatinib in addition to standard HER2-targeted therapy, including trastuzumab/pertuzumab or T-DM1. Patients were enrolled at eight centers, including Duke.
Significant Delay in Progression
After a 19.6-month follow-up, more than half of the 47 enrolled patients had not experienced worsening of the brain metastasis. Overall survival was very encouraging, with 46 out of 47 study patients still alive at the 19.6-month mark. At a 12-month follow-up, 64% of patients had no worsening of their condition. At an 18-month follow-up, 59% were alive with no progression of the disease.
Guideline Update Sought
Historically, patients treated with radiosurgery and standard therapy worsened within six months or less before their first brain metastasis. The researchers are approaching the National Comprehensive Cancer Network to request official guideline changes reflecting these findings. Senior author Carey K. Anders stated that this effort could change the standard of care in this space fairly immediately, as the test agent, tucatinib, is already available in clinic. Patients should discuss combining tucatinib with trastuzumab/pertuzumab with their oncologist.
Trial Design and Enrollment
The phase 2 BRIDGET trial enrolled patients who had recently experienced a first or second brain metastasis while cancer outside the brain remained under control. After treatment of brain lesions with radiosurgery, with or without surgical removal, patients received tucatinib in addition to standard HER2-targeted therapy consisting of trastuzumab/pertuzumab or T-DM1. The study enrolled 47 patients across eight centers, including Duke.
Sarah L. Sammons, an associate professor at the University of Maryland Greenebaum Cancer Center and an adjunct faculty member at Duke, presented the results alongside Carey K. Anders on behalf of the Hoosier Cancer Research Network.
Mechanism Of Action And Targeting
Tucatinib is a selective inhibitor of the human epidermal growth factor receptor 2 (HER2). Unlike some other HER2-targeted therapies, tucatinib is designed with a chemical structure that allows it to cross the blood-brain barrier, a highly selective semipermeable membrane that separates circulating blood from the brain extracellular fluid. This pharmacological property enables the drug to achieve therapeutic concentrations within the central nervous system, directly targeting HER2-positive cancer cells that have metastasized to the brain. Clinical data from the phase 2 BRIDGET trial demonstrated that this ability to penetrate the brain microenvironment contributed to the significant delay in disease progression observed in patients with central nervous system metastases.
In the BRIDGET trial, patients received tucatinib in combination with standard HER2-targeted therapy following local treatment of brain lesions. The trial protocol specified that tucatinib was administered alongside either trastuzumab and pertuzumab or T-DM1. This combination approach leveraged the drug’s capacity to reach intracranial sites, providing a dual mechanism of action against HER2-driven tumors both within and outside the brain. The selectivity of tucatinib for HER2-positive cells while sparing normal tissue further supports its role as a targeted option for this specific patient population.
Sources
Photo: Shixart1985 (CC BY 2.0)
