ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
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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
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standard for PET imaging of brain metastases: version 1.0.European journal of nuclear medicine and molecular imaging · 2025Guideline
- Pooled it
- A phase II study of atezolizumab in combination with stereotactic radiation for patients with triple-negative breast cancer and brain metastasis.Breast cancer research and treatment · 2026Trial
- Tucatinib-trastuzumab-capecitabine for treatment of leptomeningeal metastasis in women with HER2Nature cancer · 2026Trial
- Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases.Neuro-oncology · 2024Trial
- Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial.Nature medicine · 2024Trial
- A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Trial
- Preclinical evaluation of trastuzumab deruxtecan in a new HER2+ leptomeningeal colonization model.Cancer letters · 2026Article
- Antibody-drug conjugates in breast cancer brain and leptomeningeal metastases: mechanistic insights and therapeutic progress.Cancer metastasis reviews · 2026Review
- Interleukin-34-Induced Arg1+ Macrophages Play a Key Role in Breast Cancer Brain Metastasis.Cancer research communications · 2026Article
- Impact of trastuzumab deruxtecan (T-DXd) and brain stereotactic radiosurgery on intracranial control and radionecrosis risk in HER2-positive or -low breast cancer brain metastases.Breast (Edinburgh, Scotland) · 2026Observational
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- Expression of HER2, HER3, and TROP2 in primary tumors and brain metastases of breast cancer.Breast cancer (Tokyo, Japan) · 2026Article
- Trastuzumab deruxtecan efficacy, FcRn-facilitated penetration of the blood-tumor barrier, and distribution to tumor cells in HER2+ brain metastasis model systems.Neuro-oncology · 2026Article
- Recapitulating lung cancer metastasisOncology reports · 2026Review
- Novel treatment strategies and key research priorities for patients with breast cancer and central nervous system (CNS) metastases.NPJ breast cancer · 2025Review
- Factors associated with developing and surviving brain metastases in patients with breast cancer: a multi-center experience.BMC cancer · 2025Article
- LncPRESS1 promotes the progression and cisplatin resistance of breast cancer through upregulation of ENO1 and activation of glycolysis.Cell division · 2025Article
- The latest progress of personalized drug screening and therapy research for common clinical tumors through the PDX model platform.Journal of pharmaceutical analysis · 2025Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
purposeBrain metastases can occur in up to 50% of patients with metastatic HER2-positive breast cancer. Because patients with active brain metastases were excluded from previous pivotal clinical trials, the central nervous system (CNS) activity of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is not well characterized. EXPERIMENTAL
designWe studied how T-DXd affects growth and overall survival in orthotopic patient-derived xenografts (PDX) of HER2-positive and HER2-low breast cancer brain metastases (BCBM). Separately, we evaluated the effects of T-DXd in a retrospective cohort study of 17 patients with stable or active brain metastases.
resultsT-DXd inhibited tumor growth and prolonged survival in orthotopic PDX models of HER2-positive (IHC 3+) and HER2-low (IHC 2+/FISH ratio < 2) BCBMs. T-DXd reduced tumor size and prolonged survival in a T-DM1-resistant HER2-positive BCBM PDX model. In a retrospective multi-institutional cohort study of 17 patients with predominantly HER2-positive BCBMs, the CNS objective response rate (ORR) was 73% (11/15) while extracranial response rate was 45% (5/11). In the subset of patients with untreated or progressive BCBM at baseline, the CNS ORR was 70% (7/10). The median time on treatment with T-DXd was 8.9 (1.3-16.2) months, with 42% (7/17) remaining on treatment at data cutoff.
conclusionsT-DXd demonstrates evidence of CNS activity in HER2-positive and HER2-low PDX models of BCBM and preliminary evidence of clinical efficacy in a multi-institution case series of patients with BCBM. Prospective clinical trials to further evaluate CNS activity of T-DXd in patients with active brain metastases are warranted. See related commentary by Soffietti and Pellerino, p. 8.
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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.