RARE-01: PROLONGED DISEASE CONTROL WITH MEK INHIBITOR IN NEUROFIBROMATOSIS TYPE I ASSOCIATED GLIOBLASTOMA

BACKGROUND: Neurofibromatosis type 1 (NF1), is a common inherited autosomal dominant genetic disorder, and has been associated with glioma. Neurofibromin, encoded by the NF1 gene, downregulates the RAS-MAPK (MEK) pathway. Its loss in NF1 leads to activation of the Ras signalling pathway and has been associated with the development of multiple tumours. Preclinical testing suggests activity of MEK inhibitors in NF-1 associated tumors, but no clinical data is available. We report a case of disease control by a MEK inhibitor in recurrent NF1-associated GBM. METHODS: Case report. RESULTS: A 28 year old male with a past history of NF1 associated optic glioma, presented with a left cerebellar glioblastoma (GBM) in October 2011. The patient underwent subtotal resection, chemoradiotherapy and adjuvant temozolomide initially. He developed recurrence in June 2014 which was resected and complicated by hydrocephalus requiring a ventriculo-peritoneal shunt. He progressed on second-line carboplatin and had re-resection in August 2014. He was trialled on everolimus with stable disease for 2 months. Temozolomide was added in November 2014 and controlled disease until progression in February 2015. He was trialled on a MEK inhibitor (trametinib) and since February 2015 the patient has maintained stable disease on MRI, with reduction in oedema and size of the lesion not meeting RANO response criteria. The patient had developed an acneiform rash, which has been managed with doxycycline but has otherwise tolerated treatment well. He has had some minor clinical improvement and has been able to reduce steroid dose. CONCLUSION: NF1 associated GBM is rare. Preclinical data has suggested abnormal signalling of the RAS-MEK pathway as contributory. Here we describe the first case of substantial clinical benefit at minimal toxicity to a MEK inhibitor in a patient with treatment refractory NF1 associated GBM. This case highlights a potential promising new therapy for NF1 GBM.