Dissecting T-DXd/Dato-DXd Approvals in Breast Cancer
With the recent approvals of T-DXd and Dato-DXd, the care for breast cancer continues to evolve and expand.
In 2025, 2 important treatments for breast cancer were approved by the FDA. Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) was approved in January for patients with unresectable or metastatic HER2-low or HER2-ultralow breast cancer who have previously been treated with at least 1 type of endocrine therapy in the metastatic setting.1
Erika Hamilton, MD, director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, spoke about T-DXd’s use in the metastatic breast cancer setting. During the discussion with CancerNetwork® at the 2025 International Congress on the Future of Breast Cancer® East hosted by Physicians' Education Resource®, she also focused on emerging data from the phase 3 DESTINY-Breast11 (NCT05113251).
Additionally, Hamilton noted the FDA approval of datopotamab deruxtecan-dlnk (Datroway) for patients with previously treated unresectable or metastatic hormone receptor (HR)–positive, HER2-negative breast cancer.2
Transcript:
T-DXd is a very interesting drug, because not only do we have approval in HER2-positive disease, but we also have approval in HER2-low and have seen data, in fact, in even ultra-low, so IHC0 with some staining. This is a drug that’s getting used in the majority of patients with metastatic disease. We also have emerging data that’s going to be coming from DB11 [DESTINY-Breast11], which is looking at trastuzumab deruxtecan in the neoadjuvant space in HER2-positive disease. We anticipate more data from this compound.
Datopotamab deruxtecan, on the other hand, isn’t a HER2-targeting drug conjugate. It targets TROP2. This is our second TROP2-targeting antibody drug conjugate to join sacituzumab govitecan. If I had to leave people with one pearl, it would be to not think about all the antibody drug conjugates as a class, despite the fact that both are TROP2 targeting antibody drug conjugates, the [adverse] effects are different. With sacituzumab govitecan, we worry about diarrhea and low white blood cell count. With datopotamab deruxtecan, we worry more about nausea and mucositis, and oral stomatitis.
References
- Enhertu approved in the US as first HER2-directed therapy for patients with HER2-low or HER2-ultralow metastatic breast cancer following disease progression after one or more endocrine therapies. News release. FDA. January 27, 2025. Accessed July 16, 2025. https://tinyurl.com/5n8ab8sk
- FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic HR-positive, HER2-negative breast cancer. News release. FDA. January 17, 2025. Accessed July 16, 2025. https://tinyurl.com/3t5xbjnr
