Dr Bartsch on the TUXEDO-1 Trial of T-DXd in HER2+ Breast Cancer With Brain Metastases

Rupert Bartsch, MD, associate professor, Department of Medicine, Division of Oncology, Medical University of Vienna, discusses findings from the final analysis of the phase 2 TUXEDO-1 trial (NCT04752059) of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in patients with HER2-positive breast cancer with active brain metastases, which were presented during the 2023 San Antonio Breast Cancer Symposium.

The single-arm, prospective, single-center TUXEDO-1 trial enrolled adult patients with HER2-positive breast cancer with active brain metastases who had received prior treatment with trastuzumab (Herceptin) and pertuzumab (Perjeta), had an ECOG performance status of 0 or 1, and were not indicated for immediate local therapy. Patients received T-DXd until disease progression, unacceptable toxicity, or trial withdrawal for any other reason.

At a median follow-up of 26.5 months, the median progression-free survival (PFS) with T-DXd was 21 months (95% CI, 13.3-not reached [NR]). This median PFS was similar to that reported in the retrospective exploratory pooled analysis of T-DXd activity in patients with HER2-positive metastatic breast cancer with brain metastases who were enrolled in the phase 2 DESTINY-Breast01 (NCT03248492), phase 3 DESTINY-Breast02 (NCT03523585), and phase 3 DESTINY-Breast03 (NCT03529110) trials. In this analysis, which was presented at the 2023 ESMO Congress, the median central nervous system PFS per blinded independent central review was 18.5 months (95% CI, 13.6-23.3) with T-DXd vs 4.0 months (95% CI, 2.7-5.7) with a comparator (HR, 0.1919; 95% CI, 0.1060-0.3473).

The median overall survival in TUXEDO-1 was NR (95% CI, 22.2-NR). Bartsch notes the potential for phase 2 bias in this finding, as the patient population enrolled in TUXEDO-1 may have had relatively low-risk disease despite the presence of brain metastases. However, these survival data indicate that systemic therapies, including T-DXd, can effectively manage breast cancer brain metastases, Bartsch emphasizes. Tucatinib (Tukysa) is another effective agent for treating patients with brain metastases, as evidenced in the phase 2 HER2CLIMB trial (NCT02614794), Bartsch concludes.