FDA Approval Summary: Datopotamab Deruxtecan-dlnk for Treatment of Patients with Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer
Melanie Royce, Mirat Shah, Lijun Zhang, Joyce Cheng, Mary Kate Bonner, Melissa A. Pegues, Claudia P. Miller, Lily Leu, Lauren Price, Junshan Qiu, Jingyu Yu, Tien M. Truong, Sarah E. Dorff, Yuching Yang, Nailing Zhang, Maria Gutierrez-Lugo, Tiffany K. Ricks, William F. Pierce, Zhongjun Luo, Dana Kappel, Kirsten B. Goldberg, Stacy S. Shord, Shenghui Tang, Vishal Bhatnagar, Richard Pazdur, Paul G. Kluetz, Laleh Amiri‐Kordestani
Abstract
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.