Selumetinib for Children with Inoperable Plexiform Neurofibromas

Neurofibromatosis type 1 (NF1) is the most common inherited neurological disorder, affecting 1 in 3000 individuals. Among the many clinical manifestations, plexiform neurofibromas occur in half of patients and result in disfigurement, pain, and neurological dysfunction.

Selumetinib, an oral selective MEK inhibitor, is the first approved agent to target symptomatic plexiform neurofibromas in children with NF1. To assess its effectiveness in this setting, investigators conducted an industry-supported, open-label, phase II study of 50 patients (aged, 3–18 years) who received selumetinib (25 mg/m²) twice daily for up to 2 years.

Results were as follows:

• 70% of patients had a confirmed partial response (the primary objective); 56% had a response lasting ≥1 year.
• 68% of patients had improved clinical function, 74% had a clinically meaningful improvement in pain, 48% had improved quality of life, 78% had improved motor strength, and more than half of patients with airway obstruction had significant improvement.
• The most common adverse reactions, occurring in ≥40% of patients, were vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, acne, paronychia, and pruritus.
• Asymptomatic elevation in creatine phosphokinase was observed.

Selumetinib can also cause cardiomyopathy and ocular toxicity (including retinal vein occlusion, retinal pigment epithelial detachment, and impaired vision), but these were not observed in this trial.