First Approval for New Antibody-drug Conjugate in Breast Cancer
The FDA has issued its first approval for datopotamab deruxtecan-dlnk, a targeted therapy, for certain types of breast cancer.
The U.S. Food and Drug Administration (FDA) has approved datopotamab deruxtecan-dlnk (dato-DXd; Datroway) for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, unresectable or metastatic breast cancer that has already been treated with endocrine therapy and chemotherapy.
Dato-DXd is a type of targeted therapy known as an antibody-drug conjugate. The antibody portion, datopotamab, binds to the protein Trop-2, which is overexpressed on some types of cancer, including many breast cancers. When dato-DXd binds to Trop-2, it is brought inside the cell, where it releases deruxtecan, a drug that poisons the cell.
This is the first FDA approval for dato-DXd. Dato-DXd is the second Trop-2-targeting antibody-drug conjugate approved for pretreated HR-positive, HER2-negative advanced or metastatic breast cancer.
The approval was based on results from the multicenter, open-label, randomized phase III TROPION-Breast01 clinical trial; the data were presented at the 2023 San Antonio Breast Cancer Symposium, co-organized by the American Association for Cancer Research (AACR). Researchers enrolled 732 patients with unresectable or metastatic, HR-positive, HER2-negative breast cancer whose disease progressed on or following endocrine therapy, who were deemed unsuitable for additional endocrine therapy, and who had received one or two lines of prior chemotherapy. Patients were randomly assigned (1:1) to receive dato-DXd or chemotherapy.
Patients who received dato-DXd had higher response rates and survived longer without disease progression than those treated with chemotherapy. In the dato-DXd arm, 36% of patients experienced a response that lasted a median of 6.7 months, compared with 23% of patients in the chemotherapy arm who experienced responses lasting a median of 5.7 months. Patients in the dato-DXd arm and chemotherapy arm survived a median of 6.9 months and 4.9 months, respectively, without disease progression.
The recommended dose of dato-DXd is 6 mg/kg (up to a maximum of 540 mg) delivered once every three weeks as an intravenous infusion until disease progression or unacceptable toxicity.
Breast cancer is the most common non-skin cancer and second leading cause of cancer death among women in the United States. Around 70% of breast cancers are HR-positive and HER2-negative. According to federal statistics, it was estimated that 310,720 individuals would be diagnosed with breast cancer and 42,250 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on January 17, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.
