Commentary
Video
Author(s):
Rupert Bartsch, MD, discusses findings from the final analysis of the phase 2 TUXEDO-1 trial of trastuzumab deruxtecan in patients with HER2-positive breast cancer with active 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.