Selumetinib in Japanese pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: An open-label, phase I study

Background Plexiform neurofibromas (PN) are a manifestation of neurofibromatosis type 1 (NF1) that may cause morbidity and impact health-related quality of life (HRQoL). Selumetinib (ARRY-142886, AZD6244) is an orally available, selective, mitogen-activated protein kinase kinase 1/2 inhibitor approved for children with NF1 and symptomatic, inoperable PN in regions including the USA (aged >= 2 years), EU (>= 3 years), and Japan (>= 3 years). This open-label, single-arm, phase I study evaluated selumetinib in Japanese children with NF1 and symptomatic, inoperable PN. Methods Eligible patients (aged 3-18 years) received oral selumetinib (25 mg/m(2) twice daily) continuously in 28-day cycles in a fasted state. Primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics, efficacy, PN-related morbidities, and HRQoL. Results Twelve patients (median age 13.3 years) were enrolled, received >= 1 selumetinib dose (data cutoff: cycle 13 day 1) with median follow-up of 11.5 months. All patients had baseline PN-related morbidities, most commonly disfigurement (91.7%) and pain (58.3%). Most frequently reported any-grade adverse events were dermatologic and gastrointestinal. Objective response rate was 33.3%; median duration of response was not reached. Most patients (83.3%) had target PN volume reduction versus baseline. No patients reported worsening of PN-related morbidities. Selumetinib was rapidly absorbed with moderate-to-high inter-patient variability in maximum plasma concentration and area under the concentration-time curve from time 0-6 hours. Conclusions Consistent with results of the phase II SPRINT trial, 25 mg/m(2) selumetinib twice daily was well tolerated with a manageable safety profile in Japanese children with NF1 and symptomatic, inoperable PN.

Automated summary

This study evaluated the use of Selumetinib in Japanese children with neurofibromatosis. The results showed that the medication had a certain improvement in the patients' condition and the side effects were manageable.