Therapeutic Effects of Selumetinib on Diffuse Neurofibroma and Optic Pathway Glioma in Neurofibromatosis Type 1

Purpose Selumetinib is approved for the treatment of inoperable plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1). However, its efficacy in treating NF1-associated diffuse neurofibromas (NF1-DN) or optic pathway gliomas (NF1-OPG) remains unclear. We evaluated the safety and efficacy of selumetinib in these subgroups. Methods This was a sub-analysis of a Korean phase II, open-label trial. A total of 88 pediatric and adult patients with NF1-PN (59 children and 29 adults) were treated for at least 2 years (~ 26 cycles, 28-day cycle) with oral selumetinib (20 or 25 mg/m², or 50 mg/dose every 12 hours). Tumor volume, quality of life (QoL), and visual acuity were assessed. Results Among 88 treated patients, NF1-DN was diagnosed in 25 patients (28%), and NF1-OPG in 3 patients (3%). No serious adverse events were reported. All NF1-DN patients exhibited disfigurement, and two experienced pain. Partial response (PR) was achieved in 9 patients (36%) and confirmed PR in 6 patients (24%). The median time to PR was 6 cycles (range, 6–12), and the median time to best response was 15 cycles (range, 6–26), with a median volume change of − 18.0% (range, − 55.5% to + 36.3%). Pain improvement was observed in one patient. After cycle 26, 4 patients (16%) had PR, 11 (44%) had stable disease (SD), and 10 (40%) had progressive disease (PD). Visual impairment was noted in all three NF1-OPG patients. One patient (33%) achieved PR at cycle 12 (− 36.1% from baseline) and complete response (CR) at cycle 26; however, visual acuity did not improve. SD was maintained in the other two patients. QOL improved in 16 patients (57%). Conclusions Selumetinib demonstrated therapeutic potential for NF1-DN and NF1-OPG, although its efficacy appears to be lower than in NF1-PN.