Innovative Treatment Options of Plexiform Neurofibromas with MEK Inhibitors

Background: Neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas (PNF) are congenital peripheral nerve sheath tumors with highest growth rates especially in young children. They significantly contribute to the burden of disease with pain, disfigurement or functional impairment. However, in most cases surgery cannot achieve complete tumor removal, carries a high risk of postoperative deficits and does not prevent tumor regrowth. Therefore, the recent approval of the MEK inhibitor selumetinib for the treatment of plexiform neurofibromas provides a long-awaited novel therapeutic option.

Methods: Here, we reported our experience with MEK inhibitor treatment in 12 pediatric NF1 patients with inoperable and symptomatic plexiform neurofibromas with progressive growth. They presented with facial, cervical, thoracic, retroperitoneal, and intrahepatic tumors and were treated over periods from 3 to 24 months.

Results: Volumetric MRI after 6 months of MEK inhibitor treatment demonstrated a median tumor volume reduction of 30.6% in all patients. In addition, the majority of patients reported clinical benefit such as less pain, improved range of motion or reduced disfigurement. Therapy-related side-effects occurred in 42% of treated children, appeared to be more severe in adolescents as in younger children and mainly consisted of skin toxicity, paronychia and gastrointestinal symptoms. Only 2 patients decided to discontinue MEK inhibitor treatment after severe skin toxicity occurred and no further reduction of tumor size was observed.

Conclusion: All NF1 patients showed a tumor reduction between 20 and 55.7% after MEK inhibitor treatment.

MEK inhibition is a novel therapeutic approach for inoperable PNF with high efficacy and manageable safety profile.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
28 October 2021