Final Tuxedo-3 data presented at ESMO 2026 in Madrid show median overall survival of 10.5 months for patients with leptomeningeal disease. The phase II results indicate intracranial activity in active brain metastases but need confirmation in larger prospective trials.
Patients with leptomeningeal disease in Tuxedo-3 had median overall survival of 10.5 months, compared with the usual range of about two to six months for this population. Medsir presented the final survival data at the 2026 congress of the European Society for Medical Oncology (ESMO) in Madrid. Daiichi Sankyo announced on October 22 that the final overall-survival results would be presented as abstract 690O, a proffered paper scheduled for October 25 from 10:15 to 11:45 a.m. ESMO 2026 ran from October 23 to 27.
The phase II trial tested patritumab deruxtecan, also known as HER3-DXd, in patients with active brain metastases linked to metastatic breast cancer or advanced non-small cell lung cancer (NSCLC). A separate cohort included leptomeningeal disease caused by any solid tumour, and the presentation was classified as PanTumor. The study ran across eight hospitals in Spain and Austria. Matthias Preusser, head of the Clinical Division of Oncology at the Medical University of Vienna, was listed as the presenter of the final analysis.
Median overall survival was 7.9 months for patients with breast cancer brain metastases and 6.7 months for those with brain metastases from advanced NSCLC. Intracranial response rates were 23.8% and 30% in the respective groups.
HER3-DXd combines an antibody targeting HER3 with a payload containing a potent topoisomerase I inhibitor. HER3 is highly expressed in central nervous system metastases from breast and lung cancers, making it a potential therapeutic target. The reason for the drug’s intracranial activity remains unclear. Established brain metastases may have a more permeable blood-tumour barrier than the normal blood-brain barrier. That may help antibody-drug conjugates reach tumour tissue.
Neurological function and quality of life generally held steady during treatment. That matters in a setting where longer survival may have limited value if patients lose neurological function. The reported findings on symptoms and quality of life still warrant caution because the number of patients was relatively small.
Principal investigator Dr Matthias Preusser, head of the Clinical Division of Oncology at the Medical University of Vienna, described the results as evidence of intracranial activity. He also cautioned against treating the leptomeningeal survival figure as definitive: Tuxedo-3 was a small, single-arm phase II study with a heterogeneous patient population, so comparisons with historical survival data have limits. An earlier multicentre, single-arm phase II report on Tuxedo-3, focused on active breast-cancer brain metastases, was published in The Lancet Oncology in 2025 (volume 26, pages 1467-1478; DOI 10.1016/S1470-2045(25)00470-X).
The trial included newly diagnosed brain metastases as well as disease that had progressed after local treatment. Researchers observed responses in NSCLC both in previously untreated brain metastases and in cases that had progressed following local treatment. The findings do not yet show which patients benefit most. Researchers still need prospective evidence to assess HER3 and other possible biomarkers, and to determine how the treatment should be combined with established local and systemic therapies.
The study adds prospective evidence for patients with active central nervous system disease, who have often been underrepresented in clinical trials. Separate reporting by the outlet has covered an excavation in Cáceres where six bodies were found in a Franco-era grave.
Preusser said larger prospective trials with appropriate comparison groups are needed to confirm the findings and define patritumab deruxtecan’s role in clinical practice.
