Dr Bardia on the Efficacy and Safety of Dato-DXd in HR+/HER2– Breast Cancer

Aditya Bardia, MD, MPH, attending physician, medical oncology, Massachusetts General Hospital; associate professor, medicine, Harvard Medical School, discusses key efficacy results from the phase 3 TROPION-Breast01 trial (NCT05104866) of datopotamab deruxtecan (Dato-DXd) in hormone receptor–positive, HER2-negative breast cancer.

This open-label, global study enrolled patients who had received 1 or 2 prior lines of chemotherapy in the inoperable or metastatic setting. Patients were randomly assigned 1:1 to receive either the Trop-2–directed antibody-drug conjugate or investigator’s choice of chemotherapy.

Data presented at the 2023 San Antonio Breast Cancer Symposium show that the trial met its dual primary end point of improved progression-free survival (PFS) vs standard chemotherapy in this population, Bardia reports. At the data cutoff date of July 17, 2023, Dato-DXd produced a median PFS of 6.9 months vs 4.9 months in the chemotherapy arm by blinded independent central review (HR, 0.63; 95% CI, 0.52-0.76; P < .0001). In the Dato-DXd arm, the 6-, 9-, and 12-month PFS rates according to investigator assessment in were 55.2%, 34.7%, and 21.7%, respectively. Respective rates were 36.9%, 20.9%, and 9.9% in the chemotherapy arm.

Moreover, Dato-DXd provided a PFS benefit over chemotherapy regardless of the presence of brain metastases or prior treatment with a CDK4/6 inhibitor, Bardia states. In terms of time to treatment failure (TFST), patients in the Dato-DXd arm experienced a median TFST of 8.2 months (95% CI, 7.4-8.9) compared with 5.0 months (95% CI, 4.6-5.7) in the chemotherapy arm (HR, 0.53; 95% CI, 0.45-0.64), he details.

Additionally, Dato-DXd showed advantages in time to deterioration (TTD) in global health status/quality of life over chemotherapy, Bardia continues. The median TTD at first instance favored Dato-DXd in terms of physical functioning (HR, 0.77; 95% CI, 0.61-0.99), and pain (HR, 0.85; 95% CI, 0.68-1.07).

Safety analysis revealed that patients treated with Dato-DXD experienced a lower incidence of grade 3 or higher treatment-related adverse effects (TRAEs; 21%) vs chemotherapy (45%), Bardia says. However, any-grade TRAEs occurred in the Dato-DXd and chemotherapy arms at rates of 94% vs 86%, respectively, he notes, adding that this agent is commonly associated with AEs such as mucositis.