The leptomeningeal metastatic disease (LMD) is a serious complication in advanced solid tumors, especially for breast and lung cancer. Due to currently limited treatment options, the spread of cancer cells in the meninges leads to death within a short time. An international research team led by MedUni Vienna and AKH Vienna has now tested the active ingredient Patritumab Deruxtecan (HER3-DXD) for patients for the first time as part of a clinical study. The promising results were now presented at the annual conference of the American Society of Clinical Oncology (ASCO) in Chicago and published in the top journal “Nature Medicine”.
As part of the so-called Tuxedo-3 study, 20 patients were dealt with with LMD at seven clinics in Austria and Spain, including the University Hospital AKH Vienna, with Patritumab Deruxtecan (Her3 DXD). Her3-DXD is a so-called antibody ingredient conjugate that has not yet been approved for clinical use, but is the subject of cancer research. It consists of an antibody that ties the receptor from the receptor on the surface of certain tumor cells, and a cell poison that is coupled to it, which is introduced directly into the cancer cell. The patient participating in the current study: Inside with untreated LMD and predominantly breast or lung cancer as an underlying disease, Her3-DXD was administered intravenously every three weeks. With remarkable success, such as the investigations by the research team around Matthias Preusser, head of the clinical department for oncology of the University Clinic for internal medicine I of MedUni Vienna and AKH Vienna, show: Three months after the start of therapy with Her3 DXD, with 65 percent, significantly more study participants were: Inside still alive, neurological symptoms and quality of life remained stable or improved in most even.
The leptomeal metastatic disease is a serious form of cancer metastasis in which cancer cells spread in the meninges or in the brain fluid (cerebrospinal fluid). LMD occurs in up to ten percent of the patient: inside with advanced solid tumors-most often in the case of breast, lung cancer and melanoma. The symptoms range from headaches, nausea, neurological failures such as paralysis to visual disturbances and seizures. Without treatment, life expectancy is often only a few weeks, with therapy (radiation or chemotherapy given 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 in patient: inside with leptomingeal metastasis can develop a promising clinical effectiveness-and that with acceptable compatibility,” says Matthias Preusser. “Especially with this difficult to treat, which usually leads to death quickly, this is a promising new approach.” In addition to the tumor infestation of the brain skin, Her3-DXD is also examined in the Tuxedo-3 study in patients: inside with metastases in the brain. The aim is to pave the way for a new treatment option for patients: in addition to the in addition to ongoing admission studies with LMD and brain metastases.
Publication: Nature Medicine
Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: 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 Oberondorfer, Maximilian Marhold, Anna Sophie Berghoff, Julia Furtner, Thorsten Fuenderer, Rupert Bartsch.
https://doi.org/10.1038/s41591-025-03744-1