A drug that delivers chemotherapy directly to tumors has shown impressive activity against some of the hardest-to-reach cancer cells: those that have spread to the brain in patients with advanced HER2-positive breast cancer. The results, from an international clinical trial led by researchers at Dana-Farber Cancer Institute, reinforce previous findings about the benefits of the drug — trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate — in these patients, trial leaders say.
The results of the trial, called the DESTINY-Breast12 study, were presented today at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain, and simultaneously published in a paper in the journal Natural medicine.
The results indicate that T-DXd is a valuable new treatment option for patients with a particularly challenging form of cancer, the researchers say. “Up to half of patients with HER2-positive breast cancer develop brain metastases, which often have a worse prognosis than breast cancer that has not spread to the brain,” says Nancy Lin, MD, trial leader and senior author of the study in Natural medicineLin is the associate chief of the Division of Breast Oncology at the Dana-Farber Susan F. Smith Center for Women’s Cancers and director of the Metastatic Breast Cancer Program. Localized therapies such as surgery, radiosurgery and radiation therapy to the brain are used to treat brain metastases, but the disease typically progresses in the central nervous system (the brain and spinal cord) within six to 12 months of treatment.
Trastuzumab deruxtecan consists of the drug deruxtecan (a chemotherapy agent) attached to an antibody that targets the HER2 protein on breast cancer cells. Trastuzumab is a cornerstone treatment for HER2-positive breast cancer that has spread to other parts of the body, including the brain. But, as with treatments specifically targeting the brain, patients receiving trastuzumab often see their disease progress, often in the central nervous system.
“Additional systemic therapies are urgently needed for patients with brain metastases,” Lin said.
The DESTINY-Breast12 trial involved 504 patients with HER2-positive breast cancer treated at 78 cancer centers in Western Europe, Japan, Australia, and the U.S. Two hundred and sixty-three participants had active or stable brain metastases and 241 had no brain metastases. All had received at least one therapy prior to enrollment in the trial.
After a median follow-up of 15.4 months, progression-free survival for participants with brain metastases (the length of time patients lived with their cancer before it got worse) was a median of 17.3 months, the researchers found. Progression-free survival at 12 months was 61.6%. Seventy-one percent of participants had an intracranial objective response (a measurable shrinkage of their cancer in the central nervous system). As expected, there was also a high response rate in tumors outside the central nervous system in patients with or without brain metastases. Ninety percent of patients in both groups were alive one year after starting T-DXd treatment.
Side effects associated with T-DXd were consistent with those reported in previous studies and included nausea, constipation, neutropenia (low levels of a type of white blood cell), fatigue, and anemia. Interstitial lung disease (ILD), a known risk of T-DXd, was seen at similar rates as in previous studies, and monitoring for this potentially fatal side effect remains critical.
“Our data show that T-DXd has substantial and long-lasting activity in the brain of patients with HER2-positive breast cancer that has metastasized to the brain,” Lin said. “These results support the drug’s future use in this patient population.”