(Vienna, 30 May 2025) Leptomeningeal metastatic disease (LMD) is a serious complication of advanced solid tumours, particularly breast and lung cancer. Due to the currently limited treatment options, the spread of cancer cells to the meninges leads to death within a short period of time. An international research team led by MedUni Vienna and the University Hospital Vienna has now tested the drug patritumab deruxtecan (HER3-DXd) in patients with LMD for the first time in a clinical trial. The promising results were presented simultaneously at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago and published in the top journal Nature Medicine.
As part of the TUXEDO-3 study, 20 patients with LMD at seven clinics in Austria and Spain, including the University Hospital Vienna, were treated with patritumab deruxtecan (HER3-DXd). HER3-DXd is an antibody-drug conjugate that has not yet been approved for clinical use but is the subject of cancer research. It consists of an antibody that binds specifically to the HER3 receptor on the surface of certain tumour cells and a cell toxin coupled to it that is introduced directly into the cancer cell. Patients participating in the current study with untreated LMD and predominantly breast or lung cancer as the underlying disease were administered HER3-DXd intravenously every three weeks. With remarkable success, as shown by the investigations of the research team led by Matthias Preusser, Head of the Division of Oncology at the Department of Medicine I at MedUni Vienna and University Hospital Vienna: Three months after starting treatment with HER3-DXd, 65 percent of the study participants were still alive, significantly more than expected, and neurological symptoms and quality of life remained stable or even improved in most cases.
Leptomeningeal metastatic disease (LMD) is a serious form of cancer metastasis in which cancer cells spread to the meninges or cerebrospinal fluid (CSF). LMD occurs in up to ten percent of patients with advanced solid tumours – most commonly in breast and lung cancer and melanoma. Symptoms range from headaches, nausea and neurological deficits such as paralysis to visual disturbances and seizures. Without treatment, life expectancy is often only a few weeks, but with therapy (e.g. radiation or chemotherapy administered directly into the cerebrospinal fluid), it can be extended to several months in individual cases. The medical need for new treatment approaches is correspondingly high.
"Our study results show that intravenously administered HER3-DXd can demonstrate relevant clinical efficacy in patients with leptomeningeal metastasis – and with acceptable tolerability," says Matthias Preusser. "This is a promising new approach, especially for this difficult-to-treat disease, which usually leads to rapid death." In addition to tumour involvement of the meninges, in the TUXEDO-3 study HER3-DXd is also being investigated in patients with brain metastases. The aim is to pave the way for a new treatment option for patients with LMD and brain metastases in addition to ongoing registration studies.
Publication: Nature Medicine
Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumours: the
phase 2 TUXEDO-3.
Matthias Preusser, Javier Garde-Noguera, Juan José García-Mosquera, María Gion, Richard Greil, Miriam Arumi, Manuel Ruiz-Borrego, Antonio Llombart-Cussac, María Valero, Javier Cortés, Marta Campolier, José Antonio Guerrero, Paula González-Alonso, Carlos Jiménez Cortegana, Jose Rodríguez-Morató, Marta Vaz-Batista, Felicitas Oberndorfer, Maximilian Marhold, Anna Sophie Berghoff, Julia Furtner, Thorsten Fuereder, Rupert Bartsch.
https://doi.org/10.1038/s41591-025-03744-1