FDA Approves Dato-DXd in HR+, HER2- Breast Cancer Following TROPION-Breast01

Virginia G. Kaklamani, MD, DSc, professor of medicine in the Division of Hematology-Medical Oncology at The University of Texas Health Science Center San Antonio, discusses findings from the phase 3 TROPION-Breast01 trial (NCT05104866) of datopotamab deruxtecan (Dato-DXd) in patients with unresectable or metastatic hormone receptor-positive (HR+), HER2-negative (HER2–) breast cancer who have received prior systemic therapy.

The FDA approved Dato-DXd for the treatment of patients with HR+, HER2– breast cancer that has been previously treated with systemic therapy on January 17, 2025.

According to findings from the phase 3 TROPION-Breast01 trial, the median progression-free survival was 6.9 months (95% CI, 5.7-7.4) in the Dato-DXd arm and 4.9 months (95% CI, 4.2-5.5) in the chemotherapy arm (HR, 0.63; 95% CI, 0.52-0.76; two-sided P-value <.0001).

Transcription:

0:09 | The TROPION-Breast01 trial was a phase 3 clinical trial looking at Dato-DXd, comparing it to chemotherapy in patients with metastatic hormone receptor-positive breast cancer. As a reminder, Dato-DXd is an antibody-drug conjugate, where the antibody is an anti-TROP2 antibody, and the payload is a topoisomerase I inhibitor, which is the same payload used with trastuzumab deruxtecan [Enhertu]. The clinical trial met its first primary end point of progression-free survival with an improvement that was statistically significant compared to single-agent chemotherapy.

0:51 | Efficacy was, again, not only statistically significant but also clinically significant for our patients. I think what was impressive was the [adverse event] profile of Dato-DXd. There was very little cytopenia, which is something we have seen with other antibody-drug conjugates [ADCs]. There was some stomatitis, but it seems that a steroidal mouthwash can help with that. Additionally, there was a lower rate of interstitial lung disease than what we have seen with other ADCs like T-DXd, even though they use the same payload.

1:24 | So, this seems to be a nice approach for patients in the metastatic setting, where we really have 2 goals in therapy. We aim to improve outcomes, improve survival, and also not compromise on quality of life. An ADC with a favorable toxicity profile is very welcomed in that setting.