The Evolving Role of T-DXd Across HER2+ Breast Cancer
Key Points
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Trastuzumab deruxtecan (T-DXd) is being evaluated for various HER2-positive breast cancer indications in the DESTINY series of trials.
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Data from the DESTINY-Breast11 trial may support moving T-DXd into adjuvant therapy for early breast cancer.
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For metastatic disease with brain metastases, T-DXd may be the preferred first-line therapy based on the DESTINY-Breast09 trial outcomes.
DESTINY Trials on T-DXd for HER2+ Breast Cancer
At the 2025 San Antonio Breast Cancer Symposium, Yash Agrawal, MD, of UNC School of Medicine, sat down with Stephanie Graff, MD, of Brown University Health, to discuss recent data for HER2-positive breast cancer. Dr. Agrawal asked Dr. Graff how T-DXd and other antibody-drug conjugates are fitting into both early and advanced breast cancer treatment.
The DESTINY-Breast11 trial showed positive data for T-DXd as a neoadjuvant therapy in high-risk HER2-positive early breast cancer, and T-DXd is appealing as an anthracycline-free regimen. T-DXd may also potentially replace trastuzumab emtansine as a follow-up therapy in patients with residual disease after standard neoadjuvant chemotherapy based on the DESTINY-Breast05 trial. The field may just need longer follow-up from these trials to influence regulatory approvals and treatment guidelines in early breast cancer, said Dr. Graff.
Addressing the concern that moving T-DXd into the early breast cancer setting may leave a gap in treatment options for metastatic disease, Dr. Graff said there is no reason to save a therapy for the metastatic setting if it is the most effective first therapy that patients can receive.
In advanced or metastatic disease, T-DXd may be the preferred first-line therapy for patients with brain metastases based on the central nervous system (CNS) activity data from the DESTINY-Breast09 trial, Dr. Graff said. For patients without CNS involvement, it may still be reasonable to attempt the regimens evaluated in the PATINA or HER2CLIMB-05 trials.