Selumetinib for Managing NF1-PN in Pediatric Patients at Risk for Developing Tumor-Related Morbidity

Findings from a phase 2 study show treatment with selumetinib led to significant shrinkage of plexiform neurofibromas (PN) among pediatric patients with neurofibromas type 1 (NF1).

Selumetinib was approved by the FDA for the treatment of inoperable symptomatic PNs in pediatric patients with NF1. This phase 2 study enrolled patients with NF1 and inoperable PNs without clinically significant morbidity, but had the potential to cause symptoms, to determine the response rate to selumetinib.

A total of 25 patients were enrolled in the trial between November 12, 2015, and September 6, 2018. Patients received selumetinib at 25 mg/m2 orally twice daily (each cycle of treatment was 28 days).

Researchers performed volumetric magnetic resonance imaging analysis and outcome assessments, including patient-reported (PRO), observer-reported, and functional outcome measures, every 4 cycles for 2 years. Confirmed partial response was defined as PN volume decrease of ≥20% on at least 2 consecutive scans ≥3 months apart.

Overall, 72% of patients on the trial experienced a confirmed partial response on selumetinib. Patients received selumetinib for a median of 41 cycles at data cutoff. At baseline, approximately 50% of patients rated having some target tumor pain, which was significantly decreased by pre-cycle 13. Researchers noted that Most objectively measured baseline functions, including visual, motor, bowel/bladder, or airway function were within normal limits and did not clinically or statistically worsen during treatment.

In conclusion, selumetinib treatment resulted in significant shrinkage in the majority of patients with NF1-PN on this trial and no new PN-related symptoms developed while on the drug. In addition, PRO measures indicated decreased in tumor-related pain intensity, supporting selumetinib treatment for preventing the development of PN-related morbidities. 

Source:

Gross AM, Glassberg B, Wolters PL, et al. Neuro Oncol. 2022 Nov 2;24(11):1978-1988. doi:10.1093/neuonc/noac109.