As supported by data from the phase 3 TROPION-Breast01 trial, datopotamab deruxtecan is now an FDA-approved treatment for patients with HR-positive, HER2-negative breast cancer.
The FDA has approved Dato-DXd, a TROP2-directed ADC, for the treatment of patients with HR+, HER2– breast cancer that has been previously treated with systemic therapy.1
This approval is supported by findings from the phase 3 TROPION-Breast01 trial (NCT05104866). The median progression-free survival (PFS) was 6.9 months (95% CI, 5.7-7.4) in the Dato-DXd arm and 4.9 months (95% CI, 4.2-5.5) in the chemotherapy arm (HR, 0.63; 95% CI, 0.52-0.76; two-sided P-value <.0001).
The median overall survival (OS) was 18.6 months (95% CI, 17.3-20.1) in the Dato-DXd arm and 18.3 months (95% CI, 17.3-20.5) in the chemotherapy arm (HR, 1.01; 95% CI, 0.83-1.22; two-sided P-value was not statistically significant). The confirmed overall response rate (ORR) was 36% (95% CI, 31-42) and 23% (95% CI, 19-28) and median duration of response (DOR) was 6.7 months (95% CI, 5.6-9.8) and 5.7 months (95% CI, 4.9-6.8) in the Dato-DXd and chemotherapy arms, respectively.
According to progression-free survival (PFS) findings presented at the 2023 San Antonio Breast Cancer Symposium,3 at 6 months, the PFS rates were 53.3% vs 38.5%, respectively, and at 12 months, these rates were 25.5% vs 14.6%.
“Dato-DXd is a TROP2-directed antibody-drug conjugate. This was studied in the phase 3 TROPION-Breast01trial, which was a global study that enrolled patients with hormone receptor-positive, HER2– advanced disease who had received 1 to 2 prior lines of chemotherapy,” said Tanya Gupta, MD, medical oncologist in the Stanford University Department of Medicine, Division of Medical Oncology, in an interview with Targeted OncologyTM.
In TROPION-Breast01, Dato-DXd was compared with the investigator's choice of chemotherapy in patients with inoperable or metastatic HR+, HER2– breast cancer who have received 1 or 2 prior lines of systemic therapy. The estimated enrollment was 732 patients across sites in 10 states in the US and 19 additional countries.4
PFS and overall survival served as the primary end points of the study. Secondary end points included ORR, duration of response, PFS by investigator assessment, disease control rate, time to first subsequent therapy, and time to second subsequent therapy.
For safety, the most common adverse events (≥20%), including laboratory abnormalities, consisted of stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased alanine aminotransferase, keratitis, increased aspartate aminotransferase, and increased alkaline phosphatase.
According to the FDA, the recommended dose of Dato-DXd is 6 mg/kg (maximum of 540 mg for patients ≥90 kg), administered via intravenous infusion, once every 3 weeks on a 21-day cycle, until disease progression or unacceptable toxicity.
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