Related Experiment Video
Updated: Dec 26, 2025
An Orthotopic Sciatic Nerve Xenograft for Neurofibromatosis Type 1 Neurofibromas
Published on: October 10, 2025
Selumetinib in Children with Inoperable Plexiform Neurofibromas
Andrea M Gross1, Pamela L Wolters1, Eva Dombi1
1From the Pediatric Oncology Branch (A.M.G., P.L.W., E.D., P.W., S.M., M.C.R., D.C.P., A.C., J.T., O.K., J.G., B.C.W.) and the Clinical Pharmacology Program (C.J.P., W.D.F.), Center for Cancer Research, National Cancer Institute, and the Rehabilitation Medicine Department, Clinical Center (S.M.P), National Institutes of Health, Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick (A.B., K.H.), the Cancer Therapy Evaluation Program (M.S., L.A.D.) and the Biostatistics and Data Management Section, Center for Cancer Research (S.M.S., D.J.V.), National Cancer Institute, National Institutes of Health, Shady Grove, and Johns Hopkins University School of Medicine, Baltimore (J.O.B.) - all in Maryland; Children's Hospital of Philadelphia, Philadelphia (M.J.F., A.C.S.); Cincinnati Children's Hospital, Cincinnati (B.W.); Children's National Hospital, Washington, DC (A.K., M.B.); and Indiana University School of Medicine, Indianapolis (D.W.C., C.Z.).
Selumetinib demonstrated significant tumor shrinkage and clinical benefits in children with neurofibromatosis type 1 and inoperable plexiform neurofibromas. This phase 2 trial showed durable responses and improved quality of life, offering a promising treatment option.
Area of Science:
- Pediatric Oncology
- Genetics and Genetic Diseases
- Pharmacology and Therapeutics
Background:
- No approved therapies are currently available for inoperable plexiform neurofibromas in patients diagnosed with neurofibromatosis type 1.
- Plexiform neurofibromas significantly impact children's quality of life due to symptoms like disfigurement, motor dysfunction, and pain.
Purpose of the Study:
- To evaluate the efficacy and clinical benefit of selumetinib in children with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas.
- To determine the objective response rate and assess improvements in pain, quality of life, and function.
Main Methods:
- An open-label, phase 2 clinical trial involving 50 children with neurofibromatosis type 1 and inoperable plexiform neurofibromas.
- Patients received oral selumetinib (25 mg/m² twice daily) on a continuous 28-day cycle schedule.
- Tumor response was assessed using volumetric MRI, alongside clinical outcome assessments including pain, quality of life, disfigurement, and function.
Main Results:
- 70% of patients achieved a partial response, with 28 experiencing a durable response (lasting ≥1 year).
- Clinically meaningful improvements were observed in tumor pain reduction (2-point decrease), daily functioning, quality of life, and physical strength.
- Most frequent toxic effects included gastrointestinal issues, rash, and elevated creatine phosphokinase levels; 11 patients discontinued treatment due to toxicity or disease progression.
Conclusions:
- Selumetinib treatment resulted in durable tumor shrinkage and significant clinical benefits for most children with neurofibromatosis type 1 and inoperable plexiform neurofibromas.
- The study supports selumetinib as a potential therapeutic option for this patient population, demonstrating improvements in key symptom areas.
- Further research and long-term follow-up are warranted to fully understand the safety and efficacy profile of selumetinib in this context.
More Related Videos
09:37Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
05:44Author Spotlight: Collecting the Brain and Serum from the Same Mice Fetus to Study Brain Tumor Development
Published on: May 17, 2024