CTP-14. Treatment with MEK inhibitors in patients with low-grade gliomas in Neurofibromatosis type 1: a preliminary report

Abstract Pediatric low-grade glioma (pLGG) account for 30%–40% of all central nervous system (CNS) tumors in children. Childrens with Neurofibromatosis type 1 (NF1) have an increased risk of developing pLGG, particularly of the optic pathway and brainstem. Selumetinib and trametinib, orally bioavailable and selective MEK1/MEK2 inhibitors (MEKi), act on the MAPK pathway activated in NF1. In April 2020 the US Food and Drug Administration and in June 2021 the European Medicines Agency approved selumetinib for inoperable plexiform neurofibromas in NF1. We evaluated MEKi effcacy and safety in NF1 related pLLGs. From January 2022 to May 2025 6 patients (4 females, 2 males, median age 12,5 years, range 8-19) were admitted to our hospital for symptomatic, recurrent, inoperable pLGGs (4 optic-pathway, 1 posterior fossa, 1 quadrigeminal plate) and NF1. MEKi were administered (4 selumetinib, 2 trametinib) after disease progression for failure of previous treatments (5 patients multiple chemotherapies, one patient 1 previous chemotherapy). MRI assessment was performed every 3-6 months and radiological response was defined in accordance with RAPNO criteria. At first radiological evaluation, 5/6 patients (83,3%) showed a partial response (-57,4% mean volume reduction, range -44 to -77%) and 1/6 (16,6%) stable disease. Best response was observed after a mean of 5,6 months (range 3-11). The mean best response was -72,6% volume reduction (range -48 to -98%). At least 4 patients experienced a clinical benefit: 1 patient achieved improvement in visual field, 2 patients in vigilance and 1 patient in ataxia. No patient experienced clinical worsening. The most frequent toxicities reported were mucocutaneus. MEKi selumetinib and trametinib represent promising strategies in children with LGGs and NF1. In our small series, the treatment was effective and well tolerable. Further studies are needed to establish the possible superiority of MEK inhibitor treatment in patients with pLGGs and NF1 to avoid or delay chemotherapy treatment in this population.