EPT-05BRAFv600E INHIBITOR (VEMURAFENIB) IN PEDIATRIC PATIENTS AFFECTED BY BRAFv600E MUTATED GLIOMAS

Abstract

Gliomas are common pediatric tumors. Low-grade gliomas not amenable of gross total resection display relevant long-term disabilities; high-grade gliomas (HGG) have a low cure rates. BRAFv600E mutation is critical for the pathogenesis of 10-20%of pediatric gliomas, approaching 100%in gangliogliomas. We investigated Vemurafenib as single agent in 6 pediatric patients affected by BRAFv600E mutated gliomas (2 gangliogliomas, 1 pleomorphic xantoastrocytomas-PXA-in a patient with Down syndrome, 1 ganglioneurocytoma, 2 HGG). Median age at diagnosis was 54 months (range 1-108), F:M ratio 1:5; 3 patients received previous treatment. Vemurafenib was well tolerated: skin toxicity developed in 2/6 patients and reached grade 3 (CTC v4.0) only in one, at 960 mg/day. Two patients with ganglioglioma and 1 with HGG responded within the first 6 months, PXA has not bees assessed yetwhereas the patient with ganglioneurocytoma and the second HGG progressed under treatment, with an overall response rate of 60%. Moreover, not surprisingly, an immediate re-growth of the disease was proved after the treatment suspension in a responder, reversible with the resumption of the drug. In Conclusion Vemurafenib offers a valid treatment option in a selected population of pediatric patients affected by gliomas. Predictive markers of response are highly needed to select patients that could respond, especially in HGG. Moreover, giving the relapse/progression at the end of the treatment, further combinations are needed to achieve complete tumor eradication. The toxicity profile proved good also in a patient with Down syndrome. Confirmation in larger and prospective series is required.