RARE-35. 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 glioma subtypes. Besides more benign brain tumors, like ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50-78%) and epitheloid glio...

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Published in:Neuro-oncology (Charlottesville, Va.) Va.), 2017-11, Vol.19 (suppl_6), p.vi217-vi217
Main Authors: Burger, Michael, Ronellenfitsch, Michael, Lorenz, Nadja, Wagner, Marlies, Voss, Martin, Capper, David, Tzaridis, Theophilos, Herrlinger, Ulrich, Steinbach, Joachim, Stoffels, Gabriele, Langen, Karl-Josef, Brandts, Christian, Senft, Christian, Harter, Patrick, Baehr, Oliver
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Language:English
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Summary:BRAF V600E mutations occur frequently in malignant melanoma but are rare in most glioma subtypes. Besides more benign brain tumors, like ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50-78%) and epitheloid glioblastoma (50%) regularly exhibit BRAF mutations. Here 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 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 since 27 months, 7 months and 3 months. One patient showed a dramatic radiologic and clinical response no more than one week after start 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 results in reduced cell densitiy 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.
ISSN:1522-8517
1523-5866
DOI:10.1093/neuonc/nox168.877