MEK 抑制剂司美替尼 (selumetinib) 可减少 1 型神经纤维瘤 (NF1) 儿科患者的丛状神经纤维瘤 (PN)。其对成人 PN 的安全性和有效性以及对其他 NF1 表现（例如神经认知功能、生长减少和牛奶咖啡斑）的有效性尚不清楚。这项开放标签的 2 期试验招募了 90 名无法手术的儿童或成人 NF1 患者、有症状或潜在病态、可测量的 PN (≥ 3 cm)。 Selumetinib 的给药剂量为 20 或 25 mg/m2 或 50 mg 每 12 小时一次，持续 2 年。评估了药代动力学、PN 体积、生长参数、神经认知功能、牛奶咖啡斑和生活质量 (QoL)。 59 名儿童和 30 名成人（中位年龄，16 岁；范围，3-47）接受了治疗平均 22±5 (4-26) 个司美替尼周期。 89 名符合方案的患者中有 88 名 (98.9%) 表现出目标 PN 体积减少（中位数为 40.8%；4.2%-92.2%），81 名 (91%) 患者表现出部分缓解（体积减少≥ 20%） ）。该反应持续到第 26 个周期。儿童和成人患者的神经认知功能评分（语言理解、知觉推理、处理速度和全面智商）均显着改善（P <0.05）。青春期前患者的身高评分和生长速度均有所增加（P <0.05）。牛奶咖啡斑点强度显着降低（P <0.05）。儿童和成人的生活质量和疼痛评分均有所改善。所有不良事件均为 CTCAE 1 级或 2 级，并且在无需停药的情况下成功得到控制。塞美替尼可减少大多数儿童和成人 NF1 患者的 PN 体积，同时对多种非恶性 NF1 表现也显示出疗效。© 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。

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.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.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.Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.