Selumetinib in the treatment of plexiform neurofibromas in neurofibromatosis type 1: a 6-year prospective case series with review of the literature

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by pigmented lesions, cutaneous neurofibromas, and brain and peripheral nerve tumors. Plexiform neurofibromas (PNs) are congenital tumors whose growth tends to accelerate in the pediatric age. Selumetinib, a MEK1/2 inhibitor, is the first pharmacological treatment that has shown efficacy in reducing the size of PNs by inhibiting their key pathway, with few and moderate adverse events. The purpose of this study is to describe the effect of selumetinib in a large cohort of patients with NF1. METHODS: This is a prospective case series that describes the patients affected by NF1 with inoperable, symptomatic, or disfiguring PNs treated with selumetinib at the Institute for Maternal and Child Health IRCCS "Burlo Garofolo" in Trieste, from January 2017 to June 2023. To determine the patients' response to selumetinib, we compared the MRI volume of the PN before the beginning of the treatment with the last one available. RESULTS: Twenty-three patients with PNs were treated with selumetinib. During the follow-up period (mean time 1085 days), a tumor reduction above 20% was observed in 13 patients (57%), while 7 subjects (30%) had a tumor stabilization and 3 (13%) had a tumor growth. The median volumetric reduction was 23%. No significant correlations were found between the patients' response to treatment and the other variables considered. No severe adverse events were recorded. CONCLUSIONS: In this prospective case series selumetinib appeared to be a useful drug for the treatment of PNs.