Dr Bardia on the FDA Approval of Dato-DXd for HR+/HER2-Negative Metastatic Breast Cancer

“The totality of the data supported Dato-DXd as a superior option to standard chemotherapy in this setting, leading to its FDA approval.”

Aditya Bardia, MD, MPH, FASCO, professor, Department of Medicine, Division of Hematology/Oncology, and director, Translational Research Integration, UCLA Health Jonsson Comprehensive Cancer Center, discusses the significance of the FDA approval of datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) for patients with pretreated, hormone receptor–positive, HER2-negative metastatic breast cancer.

On January 17, 2025, the FDA approved Dato-DXd for the treatment of adult patients with unresectable or metastatic, hormone receptor–positive, HER2-negative breast cancer who had received prior endocrine therapy and at least 1 line of chemotherapy in the metastatic setting. This regulatory decision was supported by findings from the phase 3 TROPION-Breast01 trial (NCT05104866).

In the trial, patients treated with Dato-DXd (n = 365) achieved a median progression-free survival of 6.9 months (95% CI, 5.7-7.4) vs 4.9 months (95% CI, 4.2-5.5) for those given investigator’s choice of chemotherapy (n = 367; (HR, 0.63; 95% CI, 0.52-0.76; 2-sided P < .0001). The median overall survival was 18.6 months (95% CI, 17.3-20.1) in the Dato-DXd arm vs 18.3 months (95% CI, 17.3-20.5) in the chemotherapy arm (HR, 1.01; 95% CI, 0.83-1.22).

Dato-DXd is a TROP2-directed antibody-drug conjugate (ADC) that delivers a cytotoxic payload to tumor cells and spares healthy tissue, Bardia explains. The approval of this agent in breast cancer is based on data demonstrating its superior efficacy over standard chemotherapy, highlighting its potential to replace traditional cytotoxic regimens in this setting, he adds. Notably, Dato-DXd was associated with a lower incidence of grade 3/4 adverse effects compared with chemotherapy, further supporting its clinical benefit, he says.

The FDA approval of Dato-DXd provides an additional treatment option for patients with hormone receptor–positive, HER2-negative metastatic breast cancer who have progressed on endocrine-based therapy, Bardia concludes.