Neuro-oncology · 2024
Safety and efficacy of selumetinib in pediatric and adult patients with neurofibromatosis type 1 and plexiform neurofibroma.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод в очереди
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Kim Hyery, Yoon Hee Mang, Kim Eun Key, Ra Young Shin, Kim Hyo-Won, Yum Mi-Sun, Kim Min-Jee, Baek Jae Suk, Sung Yu Sub, Lee Sang Min, Lim Hyeong-Seok, Lee Byung Joo, Lim Hyun Taek, Kim Dohyung, Yoon Jihee, Bae Hyunwoo, Hwang Soojin, Choi Yun-Ha, Kim Kyung Ah, Choi In Hee, Lee Seung Won, Park Su-Jung, Lee Beom Hee
Аннотация
BACKGROUND: 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 NF1 manifestations (eg, neurocognitive function, growth reduction, and café-au-lait spots) are unknown.
METHODS: This open-label, phase II 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 hours for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated.
RESULTS: 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 < .05). Prepubertal patients showed increases in height score and growth velocity (P < .05). Café-au-lait spot intensity decreased significantly (P < .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.
CONCLUSIONS: Selumetinib decreases PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in nonmalignant diverse NF1 manifestations.
TRIAL REGISTRATION: Cris.nih.go.kr Identifier (KCT0003700).
METHODS: This open-label, phase II 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 hours for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated.
RESULTS: 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 < .05). Prepubertal patients showed increases in height score and growth velocity (P < .05). Café-au-lait spot intensity decreased significantly (P < .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.
CONCLUSIONS: Selumetinib decreases PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in nonmalignant diverse NF1 manifestations.
TRIAL REGISTRATION: Cris.nih.go.kr Identifier (KCT0003700).