SynthesisBreast (Edinburgh, Scotland)2023
Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases.
Synthesis in Breast (Edinburgh, Scotland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 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
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Defining the Prognostic Significance of BRAF V600E in Early-Stage Colon Cancer: A Systematic Review and Meta-Analysis.Current oncology (Toronto, Ont.) · 2025Pooled it
- Clinical Activity of Mitogen-Activated Protein Kinase Inhibitors in Patients With MAP2K1 (MEK1)-Mutated Metastatic Cancers.JCO precision oncology · 2025Pooled it
- Preclinical evaluation of trastuzumab deruxtecan in a new HER2+ leptomeningeal colonization model.Cancer letters · 2026Article
- 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
- Bridging the blood-brain barrier: strategies to improve delivery of biologics to tumors in the brain.Fluids and barriers of the CNS · 2026Review
- Antibody drug conjugates in metastatic brain tumors: current landscape, therapeutic potential and challenges.Journal of neuro-oncology · 2025Review
- Drug treatment of breast cancer brain metastases: progress and challenges.Discover oncology · 2025Review
- Leptomeningeal Disease: Current Approaches and Future Directions.Current neurology and neuroscience reports · 2025Review
- Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease.Journal of neuro-oncology · 2025Review
- Leptomeningeal metastatic disease: new frontiers and future directions.Nature reviews. Clinical oncology · 2025Review
- A review on intrathecal administration of medications for leptomeningeal metastases in solid tumors.Frontiers in pharmacology · 2025Review
- A potential central nervous system niche for trastuzumab deruxtecan in patients with HER2-expressing non-small cell lung cancer.Translational lung cancer research · 2024Article
- The Real-World Clinical Outcomes of Heavily Pretreated HER2+ and HER2-Low Metastatic Breast Cancer Patients Treated with Trastuzumab Deruxtecan at a Single Centre.Current oncology (Toronto, Ont.) · 2024Article
- Review
- Antibody-Drug Conjugates for the Treatment of Non-Small Cell Lung Cancer with Central Nervous System Metastases.Current oncology (Toronto, Ont.) · 2024Review
- Article
- Review
- Preclinical and clinical efficacy of trastuzumab-deruxtecan in breast cancer brain metastases: a new insight on central nervous system activity.Annals of translational medicine · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 15 institutions in 8 countries.
Funding
Abstract
backgroundPatients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM.
methodsWe conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint.
results7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine.
conclusionsThe results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.
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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.