%0 Journal Article
%T Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.
%A Kim H
%A Yoon HM
%A Kim EK
%A Ra YS
%A Kim HW
%A Yum MS
%A Kim MJ
%A Baek JS
%A Sung YS
%A Lee SM
%A Lim HS
%A Lee BJ
%A Lim HT
%A Kim D
%A Yoon J
%A Bae H
%A Hwang S
%A Choi YH
%A Kim KA
%A Choi IH
%A Lee SW
%A Park SJ
%A Lee BH
%J Neuro Oncol
%V 0
%N 0
%D 2024 Jul 8
%M 38975694
%F 13.029
%R 10.1093/neuonc/noae121
%X <B>BACKGROUND: </B>The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown.<BR><B>METHODS: </B>This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated.<BR><B>RESULTS: </B>Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation.<BR><B>CONCLUSIONS: </B>Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.