{Reference Type}: Journal Article
{Title}: Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.
{Author}: Kim H;Yoon HM;Kim EK;Ra YS;Kim HW;Yum MS;Kim MJ;Baek JS;Sung YS;Lee SM;Lim HS;Lee BJ;Lim HT;Kim D;Yoon J;Bae H;Hwang S;Choi YH;Kim KA;Choi IH;Lee SW;Park SJ;Lee BH;
{Journal}: Neuro Oncol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 8
{Factor}: 13.029
{DOI}: 10.1093/neuonc/noae121
{Abstract}: <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.