Dato-DXd Approved by FDA for HR-Positive, HER2-Negative Breast Cancer

By: JNCCN 360 Staff
Posted: Tuesday, January 21, 2025

On January 17, 2025, the U.S. Food and Drug Administration (FDA) approved datopotamab deruxtecan-dlnk (Dato-DXd; Datroway), a TROP2-directed antibody and topoisomerase inhibitor conjugate, for adults with unresectable or metastatic, hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC1+, or IHC2+/ISH–) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. Full prescribing information for Dato-DXd will be posted on Drugs@FDA.

Efficacy was evaluated in the TROPION-Breast01 (ClinicalTrials.gov identifier NCT05104866), a multicenter, open-label, randomized trial. Patients must have experienced disease progression, been deemed unsuitable for further endocrine therapy, and have received one or two lines of prior chemotherapy for unresectable or metastatic disease. Patients were excluded for a history of interstitial lung disease/pneumonitis requiring steroids, ongoing interstitial lung disease/pneumonitis, clinically active brain metastases, or clinically significant corneal disease. Patients also were excluded if they had an Eastern Cooperative Oncology Group performance status > 1.

Randomization was stratified by previous lines of chemotherapy, prior CDK4/6 inhibitor treatment, and geographic region. A total of 732 patients were randomly assigned (1:1) to receive Dato-DXd (n = 365) or investigator’s choice of chemotherapy (n = 367); eribulin (60%), capecitabine (21%), vinorelbine (10%), or gemcitabine (9%).

Median progression-free survival was 6.9 months (95% confidence interval [CI] = 5.7–7.4 months) with Dato-DXd and 4.9 months (95% CI = 4.2–5.5 months) with chemotherapy (hazard ratio = 0.63 [95% CI = 0.52–0.76]; two-sided P < .0001). Median overall survival was 18.6 months (95% CI = 17.3–20.1 months) with Dato-DXd and 18.3 months (95% CI = 17.3–20.5 months) with chemotherapy (hazard ratio = 1.01 [95% CI = 0.83–1.22]; two-sided P was not statistically significant). Confirmed objective response rates were 36% (95% CI = 31%–42%) and 23% (95% CI = 19%–28%), respectively, and the median duration of response was 6.7 months (95% CI = 5.6–9.8 months) and 5.7 months (95% CI = 4.9–6.8 months) with DatoDXd and chemotherapy, respectively.

The most common adverse reactions (≥ 20%), including laboratory abnormalities, were 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.

The recommended dose of Dato-DXd is 6 mg/kg (maximum of 540 mg for patients ≥ 90 kg), administered as an intravenous infusion, once every 3 weeks (21-day cycle), until disease progression or unacceptable toxicity.

U.S. Food and Drug Administration

---