Selumetinib Clinically Improves NF1-Associated Neurofibromas

The MEK inhibitor selumetinib showed clinical responses in the plexiform neurofibromas of adult patients with neurofibromatosis type 1 (NF1)-an indication which currently has no approved therapies available, according to new study findings. 

The phase II results were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, this week in Boston.

The researchers said patients with NF1 develop benign and malignant tumors increasingly throughout their lifetimes – and especially the particular kind of nerve tumors they studied. 

“Twenty to 50% of patients with NF1 develop plexiform neurofibromas, which are tumors that form in peripheral nerves,” said Geraldine O’Sullivan Coyne, MD, PhD, of the National Cancer Institute in Bethesda, Maryland. “While these are not cancerous, they are at risk for developing into aggressive cancers.”

The open-label, single-site study has enrolled 26 patients between 18 and 60 years of age (median age of 33), as of this past August. The target response rate they reported at the outset was 45%. 

The selumetinib was administered in 50 mg doses twice daily continuously for 28-day cycles. Of the 21 evaluable patients, 71% had a partial response (based on a 20% volume decrease). Twenty-one patients remain in the study, with 4 patients discontinuing treatment based on adverse effects or other reasons. The grade 3 drug-related toxicities included transaminitis (5 patients, 23%), rash (4 patients, 19%), and pancreatic enzyme elevation (4 patients, 19%). 

The goal is to see if these adult results translate to pediatric patients, said O’Sullivan Coyne. 

“We hope the results in adults will parallel those reported in pediatric populations,” she added.