Dissecting T-DXd/Dato-DXd Approvals in Breast Cancer

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

1. 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
2. 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