RARE-40. PERSONALIZED MEDICINE DIAGNOSIS AND RESPONSE TO TREATMENT WITH BRAF MEK INHIBITION IN A PLEOMORPHIC XANTHOASTROCYTOMA PATIENT

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2018-11, Vol.20 (suppl_6), p.vi243-vi243
• Main Authors: Pina, Yolanda, Macaulay, Robert, Walko, Christine, Evernden, Brittany, Forsyth, Peter
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noy148.1007

Abstract OBJECTIVE To highlight personalized medicine in a patient with a brafmt Pleomorphic Xanthoastrocytoma (PXA) treated with Braf-MEKi. BACKGROUND PXA is a rare low-grade astrocytoma. Rarely (as in this patient) may be malignant, accounting for less than 1% of all CNS neoplasms. BRAF-V600E mutation is usually found in PXA. Clinical trials showed BRAF tyrosine-kinase inhibitors as viable options to treat metastatic brain melanoma tumors. Recent studies showed similar therapy efficacy in primary brain tumors with BRAF mutations. Other studies suggest that brain tumors with BRAF-V600E mutation that fail BRAF inhibitors can benefit from chloroquine, an autophagy inhibitor, by overcoming the resistance of the kinase inhibitors. CASE REPORT: A 20 year-old man presented with a headache. MRI showed a large lesion, which appeared unusual for a classical Glioblastoma Multiforme (GBM). He was diagnosed with “GBM” and treated with radiation/temozolomide. Follow-up imaging showed recurrence. Histology at Moffitt showed an atypical malignant glioma that resembled PXA. Molecular testing demonstrated a BRAF-V600E mutation. Based on this, targeted therapy to inhibit Braf/Mek with Dabrafenib/Trametinib was initiated. Subsequent MRI showed decrease lesion size. After eight-months, he was given a chemotherapy holiday; however, repeat imaging showed disease progression and treatment was re-started. His disease progressed months later, and chloroquine was added to chemotherapy. Follow-up imaging showed tumor remained stable, suggesting addition of chloroquine to Dabrafenib/Trametinib halted tumor progression. Patient remains under surveillance. CONCLUSION A molecular diagnosis of PXA was made guiding targeted therapy. Molecular testing provides new avenues of diagnosis and treatment for NeuroOncology patients. Molecular interrogation should be routine for all NeuroOncology patients who are young or with unusual tumors. Addition of chloroquine overcame resistance to BRAF inhibition in this patient with a brain tumor with BRAF-V600E mutation.