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Review
. 2023 Jun 16;23(1):553.
doi: 10.1186/s12885-023-10996-y.

Treatment decisions and the use of MEK inhibitors for children with neurofibromatosis type 1-related plexiform neurofibromas

Amy E Armstrong  1 , Allan J Belzberg  2 , John R Crawford  3   4 , Angela C Hirbe  5 , Zhihong J Wang  6
Affiliations
Review

Treatment decisions and the use of MEK inhibitors for children with neurofibromatosis type 1-related plexiform neurofibromas

Amy E Armstrong et al. BMC Cancer. .

Abstract

Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with NF1 and symptomatic, inoperable PN. In a phase I/II trial, most children (approximately 70%) achieved reduction in tumor volume accompanied by improvements in patient-reported outcomes (decreased tumor-related pain and improvements in quality of life, strength, and range of motion). Selumetinib is currently the only licensed medical therapy indicated for use in pediatric patients with symptomatic, inoperable NF1-PN, with approval based on the results of this pivotal clinical study. Several other MEK inhibitors (binimetinib, mirdametinib, trametinib) and the tyrosine kinase inhibitor cabozantinib are also being investigated as medical therapies for NF1-PN. Careful consideration of multiple aspects of both disease and treatments is vital to reduce morbidity and improve outcomes in patients with this complex and heterogeneous disease, and clinicians should be fully aware of the risks and benefits of available treatments. There is no single treatment pathway for patients with NF1-PN; surgery, watchful waiting, and/or medical treatment are options. Treatment should be individualized based on recommendations from a multidisciplinary team, considering the size and location of PN, effects on adjacent tissues, and patient and family preferences. This review outlines the treatment strategies currently available for patients with NF1-PN and the evidence supporting the use of MEK inhibitors, and discusses key considerations in clinical decision-making.

Keywords: Clinical decision making; MEK inhibitors; Neurofibromatosis type 1; Plexiform neurofibroma; Surgery.

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Conflict of interest statement

AA received consultancy fees from Springworks Therapeutics; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Alexion, Prime Pharmaceuticals, and EM Partners; and has participated on a Data Safety Monitoring or Advisory Board for Alexion. AB received grants or contracts from the Neurosurgery Pain Research Institute, John Hopkins School of Medicine. JC reports no conflicts of interest. AH received royalties or licenses from Boehringer Ingelheim and Deutsches Krebsforschungszentrum; consultancy fees from Intellisphere LLC and Springworks Therapeutics; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from EM Partners; has participated on a Data Safety Monitoring or Advisory Board for Alexion and AstraZeneca Pharmaceuticals; and has received equipment, materials, drugs, medical writing support, gifts, or other services from Alexion, AstraZeneca Rare Diseases. ZW received consultancy fees, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events, and participated on a Data Safety Monitoring or Advisory Board for AstraZeneca. ZW also acts as an honorary chair for a local NF group.

Figures

Fig. 1
Fig. 1
Multidisciplinary team management of patients with NF1-PN. ENT Ear nose and throat, GI gastrointestinal, MDT multidisciplinary team, NF1 neurofibromatosis type 1, PN plexiform neurofibroma
See this image and copyright information in PMC

References

    1. Bergqvist C, Servy A, Valeyrie-Allanore L, Ferkal S, Combemale P, Wolkenstein P. Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966. Orphanet J Rare Dis. 2020;15(1):37. doi: 10.1186/s13023-020-1310-3. - DOI - PMC - PubMed
    1. Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, Lalloo F. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A. 2010;152A(2):327–332. doi: 10.1002/ajmg.a.33139. - DOI - PubMed
    1. Lammert M, Friedman JM, Kluwe L, Mautner VF. Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol. 2005;141(1):71–74. doi: 10.1001/archderm.141.1.71. - DOI - PubMed
    1. Poyhonen M, Kytölä S, Leisti J. Epidemiology of neurofibromatosis type 1 (NF1) in northern Finland. J Med Genet. 2000;37(8):632–636. doi: 10.1136/jmg.37.8.632. - DOI - PMC - PubMed
    1. Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ. Neurofibromatosis type 1. Nat Rev Dis Primers. 2017;3:17004. doi: 10.1038/nrdp.2017.4. - DOI - PubMed

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