FDA Approval Summary: Datopotamab Deruxtecan-dlnk for Treatment of Patients with Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer.

On January 17, 2025, the FDA approved datopotamab deruxtecan-dlnk (DATROWAY; Dato-DXd), a Trop-2-directed antibody and topoisomerase inhibitor conjugate, for the treatment of adults with unresectable or metastatic, hormone receptor-positive, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. Approval was based on results from TROPION-Breast01 (TB01), a multicenter, randomized, open-label trial comparing Dato-DXd with investigator's choice of chemotherapy (ICC). The trial was designed with dual primary endpoints: progression-free survival assessed by blinded independent central review according to RECIST v1.1 and overall survival (OS). TB01 demonstrated a 2-month improvement in median progression-free survival for Dato-DXd compared with ICC (6.9 vs. 4.9 months, respectively; stratified HR, 0.63; 95% confidence interval, 0.52-0.76; P < 0.0001). The OS endpoint was not met; at the final analysis of OS, the median OS was 18.6 months in the Dato-DXd arm and 18.3 months in the ICC arm (HR, 1.01; 95% confidence interval, 0.83-1.22). Although there was no OS improvement, Dato-DXd was also not associated with a clear trend toward potential detriment compared with ICC. The most commonly reported adverse reactions (≥20%) with Dato-DXd were stomatitis, nausea, fatigue, alopecia, constipation, dry eye, keratitis, and vomiting. Overall, the favorable benefit-risk profile for Dato-DXd supported its approval for the intended indication.