Open Access

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

  • Authors:
    • Michael C. Burger
    • Michael W. Ronellenfitsch
    • Nadja I. Lorenz
    • Marlies Wagner
    • Martin Voss
    • David Capper
    • Theophilos Tzaridis
    • Ulrich Herrlinger
    • Joachim P. Steinbach
    • Gabriele Stoffels
    • Karl-Josef Langen
    • Christian Brandts
    • Christian Senft
    • Patrick N. Harter
    • Oliver Bähr
  • View Affiliations

  • Published online on: October 2, 2017     https://doi.org/10.3892/or.2017.6013
  • Pages:3291-3296
  • Copyright: © Burger et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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December 2017
Volume 38 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
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APA
Burger, M.C., Ronellenfitsch, M.W., Lorenz, N.I., Wagner, M., Voss, M., Capper, D. ... Bähr, O. (2017). Dabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and leptomeningeal disease. Oncology Reports, 38, 3291-3296. https://doi.org/10.3892/or.2017.6013
MLA
Burger, M. C., Ronellenfitsch, M. W., Lorenz, N. I., Wagner, M., Voss, M., Capper, D., Tzaridis, T., Herrlinger, U., Steinbach, J. P., Stoffels, G., Langen, K., Brandts, C., Senft, C., Harter, P. N., Bähr, O."Dabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and leptomeningeal disease". Oncology Reports 38.6 (2017): 3291-3296.
Chicago
Burger, M. C., Ronellenfitsch, M. W., Lorenz, N. I., Wagner, M., Voss, M., Capper, D., Tzaridis, T., Herrlinger, U., Steinbach, J. P., Stoffels, G., Langen, K., Brandts, C., Senft, C., Harter, P. N., Bähr, O."Dabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and leptomeningeal disease". Oncology Reports 38, no. 6 (2017): 3291-3296. https://doi.org/10.3892/or.2017.6013