Trial reportNeuro-oncology2023
A phase I/II study of intrathecal trastuzumab in human epidermal growth factor receptor 2-positive (HER2-positive) cancer with leptomeningeal metastases: Safety, efficacy, and cerebrospinal fluid pharmacokinetics.
Trial report in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 4 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7).Breast (Edinburgh, Scotland) · 2024Guideline
- DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2024Guideline
- Leptomeningeal metastasis from solid tumours: EANO-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.ESMO open · 2023Guideline
- Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases.Breast (Edinburgh, Scotland) · 2023Pooled it
- Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in women with HER2Nature cancer · 2026Trial
- Phase 1 study of intracranial T cell therapy with pemetrexed for refractory brain metastases and glioblastomas.Cell reports. Medicine · 2026Article
- Peptide-Based Delivery Systems: Selected Insights into Cell-Penetrating Peptides.ACS chemical neuroscience · 2026Review
- Intrathecal nivolumab in metastatic solid tumors with leptomeningeal disease: dose escalation part of the multicenter IT-PD1/NOA-26 phase 1 trial.Nature cancer · 2026Article
- Antibody-drug conjugates in breast cancer brain and leptomeningeal metastases: mechanistic insights and therapeutic progress.Cancer metastasis reviews · 2026Review
- Bridging the blood-brain barrier: strategies to improve delivery of biologics to tumors in the brain.Fluids and barriers of the CNS · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Case report: Systemic T-DXd and bevacizumab plus local therapy prolongs survival in breast cancer leptomeningeal metastasis: a case series and literature review.Frontiers in oncology · 2026Article
- Serial CSF CA19-9 monitoring and CSF genomic profiling in ERBB2-mutant lung adenocarcinoma with leptomeningeal metastasis: a case report.Frontiers in oncology · 2026Article
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- Intrathecal pemetrexed in patients with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistant refractory leptomeningeal metastasis lung adenocarcinoma: a retrospective study.Journal of thoracic disease · 2025Article
- Point/Counterpoint: Intrathecal therapy for patients with leptomeningeal metastases from solid tumors.Neuro-oncology · 2025Article
- A HER3-targeting antibody-drug conjugate for leptomeningeal metastasis.Nature medicine · 2025Article
- Drug treatment of breast cancer brain metastases: progress and challenges.Discover oncology · 2025Review
- Review
- Leptomeningeal Disease: Current Approaches and Future Directions.Current neurology and neuroscience reports · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundPatients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum-tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive leptomeningeal disease (LMD).
methodsThis multicenter study enrolled 34 LMD patients in a combined phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the phase I; the phase II was limited to HER2-positive breast cancer.
resultsIntrathecal trastuzumab was well-tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80 mg were included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for phase II dose treated patients was 8.3 months (95% CI 5.2-19.6). The phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2-20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable cerebrospinal fluid (CSF) concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations.
conclusionThis study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.