Patritumab deruxtecan activity in breast cancer patients with brain metastases

New data from the TUXEDO-3 phase 2 trial, recently published on The Lancet Oncology, show that  patritumab deruxtecan (HER3-DXd) could offer a novel therapeutic option in patients with metastatic breast cancer and active brain metastases, as already suggested by previous data.

For the TUXEDO-3 phase 2 trial, 21 female patients with heavily pretreated advanced breast cancer (luminal, HER2-positive breast cancer or triple-negative breast cancer) were enrolled and treated for a median of 3 months with HER3-DXd. This novel antibody-drug conjugate targets HER3, which is overexpressed in brain metastases of metastatic breast cancer; as authors underscore, «A key therapeutic goal is to delay or avoid whole-brain radiotherapy while providing effective systemic treatment. Trastuzumab deruxtecan and the tyrosine-kinase inhibitor tucatinib are established systemic treatment options for HER2-positive breast cancer with brain metastasis. However, disease progression will eventually occur and systemic approaches are needed for luminal and triple-negative breast cancer, for which local therapy remains the standard of care». For the study, the threshold for the primary endpoint was at least 15% of patients having intracranial response. After a median follow-up of 4.9 months, five (24%) patients had an intracranial response irrespective of the breast cancer subtype; serious adverse events occurred in six (29%) patients and no treatment-related deaths were reported. As authors conclude, «We showed clinically meaningful activity in a heavily pretreated population and, importantly, both quality of life and neurocognitive function were preserved, underscoring the potential clinical value of this approach. The TUXEDO-3 trial establishes a proof of principle for the activity of antibody–drug conjugate-based therapy in patients with breast cancer and brain metastases beyond the HER2-positive setting, highlighting an important opportunity to address unmet needs in other subtypes».