Durable responses to long-term selumetinib in Chinese pediatric NF1 patients with inoperable plexiform neurofibromas.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
BACKGROUND: This study provides the first long-term efficacy and safety data of selumetinib in Chinese pediatric patients with inoperable symptomatic plexiform neurofibromas (PN) associated with neurofibromatosis type 1 (NF1). METHODS: In this single-center Phase I clinical trial(NCT04590235), we enrolled children with NF1-related PN aged 3 to <18 years and treated them with selumetinib at a dose of 25 mg/m2 twice daily in 28-day cycles until disease progression or intolerance. The study consisted of a predefined treatment phase, with a final data cutoff (DCO) on August 15, 2023, followed by an extended follow-up period with a latest DCO on March 1, 2025. Tumor response was assessed by volumetric MRI using Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria. Safety was evaluated per CTCAE v5.0. Patient-reported outcomes included pain, health-related quality of life (HRQoL), and exploratory growth and dermatologic assessments. Prior PK data have been reported. RESULTS: A total of 16 children were enrolled (median age 11 years; range 4-16) . At the final DCO, the median follow-up duration was 25 cycles (range, 24-33). With extended follow-up at the latest DCO, patients received treatment for a median of 45 cycles (range, 20-52). The objective response rate (ORR) remained 81.3% (95% CI, 54.4%-96.0%) at both the final and latest DCOs, demonstrating durable tumor responses over long-term treatment. At Cycle 42 (predefined assessment timepoint at the latest DCO), the median best percentage reduction in target PN volume was 47.3%. All patients experienced at least one adverse event (AE), while 12 of 16 patients (75.0%) experienced at least one treatment-related adverse event (TRAE). Most TRAEs were Grade 1-2 and consistent with the known safety profile of selumetinib. No Grade ≥3 TRAEs were observed. Treatment was associated with improvements in pain and HRQoL scores. Exploratory analyses suggested increased growth velocity and reduced café-au-lait macule pigmentation in prepubertal patients. CONCLUSIONS: Long-term selumetinib treatment in Chinese pediatric patients with NF1-related PN resulted in durable tumor responses and sustained pain improvement. No new safety signals were identified, although ongoing monitoring of known adverse events remains warranted. TRIAL REGISTRATION: NCT04590235, registered at ClinicalTrials.gov, URL: https://clinicaltrials.gov/study/NCT04590235?term=NCT04590235&rank=1.