Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/32756
Title: Understanding the activity of antibody-drug conjugates in primary and secondary brain tumours.
Austin Authors: Mair, Maximilian J;Bartsch, Rupert;Le Rhun, Emilie;Berghoff, Anna S;Brastianos, Priscilla K;Cortes, Javier;Gan, Hui K ;Lin, Nancy U;Lassman, Andrew B;Wen, Patrick Y;Weller, Michael;van den Bent, Martin;Preusser, Matthias
Affiliation: Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.;Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria.
Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.;Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Olivia Newton-John Cancer Wellness and Research Centre
Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.;Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
International Breast Cancer Center (IBCC), Pangaea Oncology, Quirónsalud Group, Madrid and Barcelona, Spain.;Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain.;Medical Scientia Innovation Research (MEDSIR), Barcelona, Spain.
Cancer Therapies and Biology Group, Centre of Research Excellence in Brain Tumours, Olivia Newton-John Cancer Wellness and Research Centre, Austin Hospital, Heidelberg, VIC, Australia.;La Trobe University School of Cancer Medicine, Heidelberg, VIC, Australia.;Department of Medicine, University of Melbourne, Heidelberg, VIC, Australia.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Division of Neuro-Oncology, Department of Neurology, Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and New York-Presbyterian Hospital, New York, NY, USA.
Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.;Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
The Brain Tumour Center, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands.
Issue Date: Jun-2023
Date: 2023
Publication information: Nature Reviews. Clinical Oncology 2023-06; 20(6)
Abstract: Antibody-drug conjugates (ADCs), a class of targeted cancer therapeutics combining monoclonal antibodies with a cytotoxic payload via a chemical linker, have already been approved for the treatment of several cancer types, with extensive clinical development of novel constructs ongoing. Primary and secondary brain tumours are associated with high mortality and morbidity, necessitating novel treatment approaches. Pharmacotherapy of brain tumours can be limited by restricted drug delivery across the blood-brain or blood-tumour barrier, although data from phase II studies of the HER2-targeted ADC trastuzumab deruxtecan indicate clinically relevant intracranial activity in patients with brain metastases from HER2+ breast cancer. However, depatuxizumab mafodotin, an ADC targeting wild-type EGFR and EGFR variant III, did not provide a definitive overall survival benefit in patients with newly diagnosed or recurrent EGFR-amplified glioblastoma in phase II and III trials, despite objective radiological responses in some patients. In this Review, we summarize the available data on the central nervous system activity of ADCs from trials involving patients with primary and secondary brain tumours and discuss their clinical implications. Furthermore, we explore pharmacological determinants of intracranial activity and discuss the optimal design of clinical trials to facilitate development of ADCs for the treatment of gliomas and brain metastases.
URI: https://ahro.austin.org.au/austinjspui/handle/1/32756
DOI: 10.1038/s41571-023-00756-z
ORCID: 0000-0002-6537-3874
0000-0002-9408-3278
0000-0003-4470-8425
0000-0001-7623-1583
0000-0001-7319-8546
0000-0002-1748-174X
0000-0001-5710-5127
0000-0003-3541-2315
Journal: Nature Reviews. Clinical Oncology
PubMed URL: 37085569
ISSN: 1759-4782
Type: Journal Article
Appears in Collections:Journal articles

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