Personalized Treatment for a Patient with a BRAF V600E-Mutation Using Dabrafenib and Tumor Treatment Fields (TTFields; NovoTTF -100A) Device in a Glioblastoma Arising from Ganglioglioma (P3.280)

Background/objective: Glioblastoma multiforme (GBM) patients have low survival rate despite multimodality treatments with surgery, radiation and chemotherapy. Recurrent GBM fare worse (6 month’s progression-free survival - 9[percnt]), reflecting minimal benefit from salvage treatment. Here we report clinical history, molecular finding and treatment response in a patient with BRAF V 600 mutated GBM arising from a ganglioglioma. Method: H&E staining and comprehensive genomic profiling (CGP) via Foundation One were performed on the tumor sample from a male patient undergoing treatment at the Department of Neuro-Oncology at Baylor University Medical Center. Presentation: A 25 year old man presented to our clinic in 2013 with residual/recurrent high-grade glioma (HGG) arising from a long standing ganglioglioma. The original diagnosis of ganglioglioma was made in 1999. Patient underwent sub-total resection and monitoring. In 2013, craniotomy, resection of mass and biopsy was performed. The pathology was suggestive of HGG with features of GBM versus an anaplastic ganglioglioma. A CGP performed on the tumor tissue detected BRAF V600E mutation and homozygous losses in CDKN2A, CDKN2B, and BCOR. Results: The patient was eligible for participating in a clinical trial (NCT00916409) of NovoTTF-100A device with concurrent-radiation+chemotherapy (CCRT). He relapsed four months after completion of his CCRT, with MRI showing areas of enhancements. TMZ was discontinued and he was offered dabrafenib, an oral selective inhibitor of BRAF V600E, with continued use of Novo-TTF. At the time of this report, after 23 months of treatment with dabrafenib+Novo-TTF, patient’s recent MRI shows a complete response in all areas with no active lesions or new areas of enhancement. Conclusion: Our report suggests: 1) targeted therapy with dabrafenib matched the genomic alterations relative to chemotherapy (temozolomide) while being treated with Novo-TTF 2) longstanding response (historically >1year) indicates possible synergies of targeted therapy with Novo-TTF and/or novel mechanisms to counteract the resistance to treatments. Disclosure: Dr. Melguizo has received personal compensation for activities with Novocure Inc. as an consultant. Dr. Meletath has nothing to disclose. Dr. Pavlick has received personal compensation for activities with Foundation Medicine. Dr. Snipes has nothing to disclose. Dr. Rajaram has nothing to disclose. Dr. Brennan has received compensation for activities with Foundation Medicine as an employee. Dr. Hamilton has nothing to disclose. Dr. Chmielecki holds stock and/or stock options in Foundation Medicine. Dr. Elvin has received personal compensation for activities with Foundation Medicine. Dr. Palma holds stock and/or stock options in Foundation Medicine. Dr. Ross has received compensation for serving on the Foundation of Medicine. Dr. Miller has received personal compensation for activities with Foundation Medicine as an employee. Dr. Stephens has received personal compensation for activities with Foundation Medicine as an employee. Dr. Ali has received compensation from Foundation Medicine as an employee and having an equity interest. Dr. Beiss has received personal compensation for activities with Novocure as an employee. Dr. Beiss has equity interest in Novocure.