A drug known as trastuzumab deruxtecan (T-DXd) has shown impressive activity against difficult-to-treat cancer cells that have spread to the brain in patients with advanced HER2-positive breast cancer. These findings come from the DESTINY-Breast12 study, led by researchers from Dana-Farber Cancer Institute, and were presented at the European Society of Medical Oncology (ESMO) Congress 2024 in Barcelona. The results, published in Nature Medicine, highlight T-DXd as a promising new treatment option for patients facing this challenging form of cancer. Brain metastases are common in HER2-positive breast cancer, with a prognosis that is often worse than breast cancer that has not spread to the brain.
The drug Trastuzumab deruxtecan consists of a chemotherapy agent linked to an antibody that targets the HER2 protein on breast cancer cells. Although trastuzumab is a standard treatment for HER2-positive breast cancer that has spread, including to the brain, patients often see their disease progress in the central nervous system. Patients with brain metastases are particularly in need of additional systemic therapies, making the results of the DESTINY-Breast12 trial significant for the success of T-DXd in treating these patients. The trial included 504 patients with HER2-positive breast cancer from various regions who had previously received at least one therapy before enrolling in the trial.
After a median follow-up of 15.4 months, participants with active or stable brain metastases showed a progression-free survival of 17.3 months. The 12-month progression-free survival rate was 61.6%, with 71% of participants experiencing an intracranial objective response. Additionally, there was a high response rate in tumors outside of the central nervous system for both patients with brain metastases and those without. Ninety percent of patients in both groups were alive one year after starting T-DXd treatment. The side effects of T-DXd were consistent with previous studies, including nausea, constipation, neutropenia, fatigue, and anemia, with interstitial lung disease observed at similar rates to prior research.
These results show that T-DXd has substantial and durable activity in the brains of patients with HER2-positive breast cancer that has metastasized there. This supports the ongoing use of T-DXd in this patient population as a valuable treatment option. The urgent need for systemic therapies for patients with brain metastases in HER2-positive breast cancer makes these findings significant in providing hope for improved outcomes in a particularly challenging form of cancer. The persistent response rates and tolerable side effects of T-DXd make it a promising option for patients in need of effective treatments for this aggressive disease.
