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Abstract
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.
Glossary
- AE=
- adverse event;
- CK=
- creatine kinase;
- CTCAE=
- Common Terminology Criteria for Adverse Events;
- DCR=
- disease control rate;
- MAPK=
- mitogen-activated protein kinase;
- NF1=
- neurofibromatosis type 1;
- ORR=
- objective response rate;
- PN=
- plexiform neurofibromas;
- STIR=
- short-tau inversion recovery
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
CME Course: NPub.org/cmelist
- Received August 4, 2021.
- Accepted in final form December 27, 2021.
- © 2022 American Academy of Neurology
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