Dabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and leptomeningeal disease

  • BRAF V600E mutations occur frequently in malignant melanoma, but are rare in most malignant glioma subtypes. Besides, more benign brain tumors such as ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50-78%) and epitheloid glioblastoma (50%) regularly exhibit BRAF mutations. In the present study, we report on three patients with recurrent malignant gliomas harbouring a BRAF V600E mutation. All patients presented with markedly disseminated leptomeningeal disease at recurrence and had progressed after radiotherapy and alkylating chemotherapy. Therefore, estimated life expectancy at recurrence was a few weeks. All three patients received dabrafenib as a single agent and all showed a complete or nearly complete response. Treatment is ongoing and patients are stable for 27 months, 7 months and 3 months, respectively. One patient showed a dramatic radiologic and clinical response after one week of treatment. We were able to generate an ex vivo tumor cell culture from CSF in one patient. Treatment of this cell culture with dabrafenib resulted in reduced cell density and inhibition of ERK phosphorylation in vitro. To date, this is the first series on adult patients with BRAF-mutated malignant glioma and leptomeningeal dissemination treated with dabrafenib monotherapy. All patients showed a dramatic response with one patient showing an ongoing response for more than two years.

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Author:Michael Christian BurgerORCiDGND, Michael Wilfried RonellenfitschORCiDGND, Nadja Irene LorenzGND, Marlies Wagner, Martin VossORCiD, David Capper, Theophilos Tzaridis, Ulrich Herrlinger, Joachim Peter SteinbachORCiDGND, Gabriele Stoffels, Karl-Josef Langen, Christian Hubertus BrandtsORCiDGND, Christian Alexander SenftORCiDGND, Patrick Nikolaus HarterORCiDGND, Oliver Bähr
URN:urn:nbn:de:hebis:30:3-471650
DOI:https://doi.org/10.3892/or.2017.6013
ISSN:1791-2431
ISSN:1021-335X
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29039591
Parent Title (English):Oncology reports
Publisher:Spandidos Publ.
Place of publication:Athens
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/10/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/09/04
Tag:BRAF; BRAF V600E; PXA; dabrafenib; glioblastoma; glioma; leptomeningeal disease; pleomorphic xanthoastrocytoma
Volume:38
Issue:6
Page Number:6
First Page:3291
Last Page:3296
Note:
Copyright: © Burger et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
HeBIS-PPN:437862097
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0