Impact of trametinib on the neuropsychological profile of NF1 patients.

MEK inhibitor Neurofibromatosis type 1 Neuropsychological profile Trametinib

Journal

Journal of neuro-oncology

ISSN: 1573-7373

Titre abrégé: J Neurooncol

Pays: United States

ID NLM: 8309335

Informations de publication

Date de publication:
05 Mar 2024

Historique:

received: 26 01 2024

accepted: 26 02 2024

medline: 6 3 2024

pubmed: 6 3 2024

entrez: 5 3 2024

Statut: aheadofprint

Résumé

The use of trametinib in the treatment of pediatric low-grade gliomas (PLGG) and plexiform neurofibroma (PN) is being investigated in an ongoing multicenter phase II trial (NCT03363217). Preliminary data shows potential benefits with significant response in the majority of PLGG and PN and an overall good tolerance. Moreover, possible benefits of MEK inhibitor therapy on cognitive functioning in neurofibromatosis type 1 (NF1) were recently shown which supports the need for further evaluation. Thirty-six patients with NF1 (age range 3-19 years) enrolled in the phase II study of trametinib underwent a neurocognitive assessment at inclusion and at completion of the 72-week treatment. Age-appropriate Wechsler Intelligence Scales and the Trail Making Test (for children over 8 years old) were administered at each assessment. Paired t-tests and Reliable Change Index (RCI) analyses were performed to investigate change in neurocognitive outcomes. Regression analyses were used to investigate the contribution of age and baseline score in the prediction of change. Stable performance on neurocognitive tests was revealed at a group-level using paired t-tests. Clinically significant improvements were however found on specific indexes of the Wechsler intelligence scales and Trail Making Test, using RCI analyses. No significant impact of age on cognitive change was evidenced. However, lower initial cognitive performance was associated with increased odds of presenting clinically significant improvements on neurocognitive outcomes. These preliminary results show a potential positive effect of trametinib on cognition in patients with NF1. We observed significant improvements in processing speed, visuo-motor and verbal abilities. This study demonstrates the importance of including neuropsychological evaluations into clinical trial when using MEK inhibitors for patients with NF1.

Identifiants

DOI: 10.1007/s11060-024-04624-3 PMID: 38443693

pubmed: 38443693

doi: 10.1007/s11060-024-04624-3

pii: 10.1007/s11060-024-04624-3

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

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