Datopotamab Deruxtecan Approved for HR-Positive, HER2-Negative Breast Cancer

On January 17, 2025, the US Food and Drug Administration (FDA) approved the Trop-2–directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) for the treatment of patients with unresectable or metastatic, HR-positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. This regulatory decision was based on results from the TROPION-Breast01 trial.

In this multicenter, open-label trial, 723 patients were randomized on a 1-to-1 basis to receive Dato-DXd (n = 365), or the investigator’s choice of chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine; n = 367). All patients were required to have experienced disease progression, to have been deemed unsuitable for further endocrine therapy, and to have received 1 or 2 lines of prior chemotherapy for unresectable or metastatic disease. Randomization was stratified based on previous lines of chemotherapy, prior CDK4/6 inhibitor treatment, and geographical region. The major efficacy measure was progression-free survival (PFS) by blinded independent central review, and overall survival (OS). Secondary outcomes included objective response rate (ORR) and duration of response (DOR) by blinded independent central review.

The median PFS was 6.9 months in the Dato-DXd arm and 4.6 months in the chemotherapy arm (hazard ratio [HR], 0.63; 2-sided P < .0001). The median OS was 18.6 months in the Dato-DXd arm and 18.3 months in the chemotherapy arm (HR, 1.01; 2-sided P not statistically significant). The confirmed ORR were 36% and 23%, and the median DOR were 5.7 months and 5.7 months, respectively.

The most common adverse events experienced by ≥ 20% of patients and included lab abnormalities were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphate.

The recommended dose for datopotamab deruxtecan is 6 mg/kg, with a maximum of 540 mg for patients ≥ 90 kg, administered by intravenous infusion, once every 3 weeks in 21-day cycles until disease progression or unacceptable toxicity.

Source:

FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. Accessed on January 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast