Selumetynib — pierwszy lek skuteczny w terapii nerwiakowłókniaków splotowatych w przebiegu neurofibromatozy typu 1

Abstract

Plexiform neurofibromas progress and increase their size throughout the patient’s life, causing body deformity, disability, and higher mortality. Complete tumour resection is often dificult due to the large size of the plexiform neurofibroma and nerve infiltration. Treatment with MEK inhibitors appears to be a promising therapeutic option that allows reducing the mass of tumours. In the clinical trial NCT01362803 on the effect of selumetinib on inoperable plexiform neurofibromas in type 1 neurofibromatosis, children aged 3 to 18 years were involved. 74% of patients showed a partial response, defined as a reduction of at least 20% in tumour volume. Progression-free time was on average 3 years. The best results were observed after the 16th cycle of therapy. In addition to reducing tumour volume, a significant clinical reduction in pain intensity has also been demonstrated, which has resulted in an improvement in overall quality of life and daily functioning. At the same time, 78% of children from the control sample showed an increase of at least 20% in neurofibroma size. The results of studies on the effects of selumetinib in the adult population are also promising. Selumetinib treatment was well tolerated in both age groups. Gastrointestinal and skin complaints were most commonly observed. Most symptoms could be alleviated by appropriate treatment. More serious but rarer complications were cardiomyopathy and ophthalmic complications.