Patritumab Deruxtecan Shows Promise for Leptomeningeal Metastases Treatment

August 8, 2025
Patritumab Deruxtecan Shows Promise for Leptomeningeal Metastases Treatment

Patritumab deruxtecan, a novel antibody-drug conjugate (ADC), has demonstrated significant potential in improving survival rates for patients suffering from leptomeningeal metastatic disease (LMD) linked to solid tumors. Findings from the phase 2 TUXEDO-3 trial, published on May 30, 2025, in Nature Medicine, indicate that 65% of evaluated patients remained alive after three months of treatment, exceeding the predefined threshold of 25% necessary for clinical relevance (Preusser et al., 2025).

Leptomeningeal metastases, characterized by the infiltration of cancer cells into the leptomeninges or cerebrospinal fluid (CSF), pose a serious challenge within oncology, often resulting in a dismal prognosis. Current therapies yield a median overall survival of only 2 to 6 months, highlighting the critical need for innovative treatment options (Favourable results of patritumab deruxtecan, 2025).

In the TUXEDO-3 trial, which included 20 evaluable patients between January and July 2024, participants primarily presented with breast (60%) and lung (30%) cancers. The study’s design involved administering patritumab deruxtecan at a dose of 5.6 mg/kg intravenously every three weeks, with a median follow-up period of 5.4 months. The study's results revealed a Kaplan-Meier estimated 3-month and 6-month overall survival rate of 69.6% and 58.9%, respectively. Additionally, the objective response rates for intracranial and extracranial lesions were 11.1% and 30.8%, respectively, underscoring the treatment's efficacy (Preusser et al., 2025).

The safety profile of patritumab deruxtecan was consistent with prior studies, with no new safety signals reported. The most common adverse events included anemia (40.9%), nausea (31.8%), and neutropenia (27.3%), with a serious adverse event rate of 18.2%. Importantly, there were no treatment-related deaths observed during the trial (Preusser et al., 2025).

These findings are particularly significant given the limited treatment landscape for patients with LMD. While current treatment guidelines primarily recommend radiotherapy or intrathecal pharmacotherapy, the ability of patritumab deruxtecan to improve or stabilize neurological symptoms suggests its potential as a valuable systemic treatment option (Favourable results of patritumab deruxtecan, 2025).

According to Dr. Michael Preusser, lead investigator and oncologist at the Medical University of Vienna, "Overall, our data show clinically relevant activity of HER3-DXd in patients with LMD of solid cancers and may open the path to novel treatment options for this condition characterized by high morbidity and mortality."

Experts advocate for further investigations to compare patritumab deruxtecan with other therapies, such as trastuzumab deruxtecan (T-DXd; Enhertu), particularly given the heterogeneous nature of LMD across various solid tumors (Preusser et al., 2025; Favourable results of patritumab deruxtecan, 2025). The TUXEDO-3 trial’s outcomes underscore the need for robust clinical trials to refine treatment guidelines for these challenging patient populations. As the field of oncology continues to evolve, the exploration of HER3 as a therapeutic target in central nervous system metastases remains crucial for advancing patient care.

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Patritumab DeruxtecanLeptomeningeal MetastasesTUXEDO-3 TrialSolid TumorsOncologyAntibody-Drug ConjugateCancer TreatmentClinical TrialsBreast CancerLung CancerCerebrospinal FluidSurvival RatesNeurological SymptomsPatient SafetyCancer ResearchPhase 2 StudyMedical University of ViennaDr. Michael PreusserECOG Performance StatusAdverse EventsSystemic TherapyTrastuzumab DeruxtecanCNS MetastasesMorbidityMortalityClinical GuidelinesTreatment OptionsInnovative TherapiesCancer PrognosisHealthcare Advances

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