Efficacy and Safety of Selumetinib in Pediatric Patients With Neurofibromatosis Type 1: A Systematic Review and Meta-analysis

Neurology. 2022 Mar 1;98(9):e938-e946. doi: 10.1212/WNL.0000000000013296. Epub 2022 Jan 11.


Background and objectives: Although the recent approval of selumetinib is expected to transform the management of children with neurofibromatosis type 1 (NF1), particularly those with symptomatic and inoperable plexiform neurofibromas, no systematic review has summarized its efficacy and safety based on the latest studies. This study was conducted to systematically evaluate the efficacy and safety of selumetinib in children with NF1.

Methods: Original articles reporting the efficacy and safety of selumetinib in patients with NF1 were identified in PubMed and EMBASE up to January 28, 2021. The pooled objective response rates (ORRs) and disease control rates (DCRs) were calculated using the DerSimonian-Laird method based on random-effects modeling. The pooled proportion of adverse events (AEs) was also calculated. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system.

Results: Five studies involving 126 patients were included in our analysis. The studies had a very low to moderate quality of the evidence. The pooled ORR was 73.8% (95% CI 57.3%-85.5%) and the DCR was 92.5% (95% CI 66.5%-98.7%). The 2 most common AEs were diarrhea, which had a pooled rate of 63.8% (95% CI 52.9%-73.4%), and an increase in creatine kinase levels, which had a pooled rate of 63.3% (95% CI 35.6%-84.3%).

Discussion: Our results indicate that selumetinib is an effective and safe treatment for pediatric patients with symptomatic, inoperable plexiform neurofibromas. Further larger-scale randomized controlled studies are needed to confirm the long-term outcome of patients treated with this drug.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Benzimidazoles / adverse effects
  • Child
  • Diarrhea
  • Humans
  • Neurofibroma, Plexiform*
  • Neurofibromatosis 1* / complications
  • Neurofibromatosis 1* / drug therapy


  • AZD 6244
  • Benzimidazoles