Impact of trametinib on the neuropsychological profile of NF1 patients

• Published in: Journal of neuro-oncology Vol. 167; no. 3; pp. 447 - 454
• Main Authors: Lalancette, Eve, Cantin, Édith, Routhier, Marie-Ève, Mailloux, Chantal, Bertrand, Marie-Claude, Kiaei, Dorsa Sadat, Larouche, Valérie, Tabori, Uri, Hawkins, Cynthia, Ellezam, Benjamin, Décarie, Jean-Claude, Théoret, Yves, Métras, Marie-Élaine, McKeown, Tara, Ospina, Luis H., Vairy, Stéphanie, Ramaswamy, Vijay, Coltin, Hallie, Sultan, Serge, Legault, Geneviève, Bouffet, Éric, Lafay-Cousin, Lucie, Hukin, Juliette, Erker, Craig, Caru, Maxime, Dehaes, Mathieu, Jabado, Nada, Perreault, Sébastien, Lippé, Sarah
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-05-2024; Springer Nature B.V
• Subjects: Adolescent; Adult; Age; Antineoplastic Agents - adverse effects; Brain Neoplasms - complications; Brain Neoplasms - drug therapy; Brain Neoplasms - psychology; Child; Child, Preschool; Clinical significance; Cognition; Cognitive ability; Female; Glioma - complications; Glioma - drug therapy; Glioma - psychology; Humans; Information processing; Intelligence; Male; Medicine; Medicine & Public Health; MEK inhibitors; Neurofibromatosis; Neurofibromatosis 1 - complications; Neurofibromatosis 1 - drug therapy; Neurofibromatosis 1 - psychology; Neurology; Neuropsychological Tests; Neuropsychology; Oncology; Patients; Pediatrics; Plexiform neurofibroma; Protein Kinase Inhibitors - therapeutic use; Pyridones - therapeutic use; Pyrimidinones - administration & dosage; Pyrimidinones - pharmacology; Pyrimidinones - therapeutic use; Recklinghausen's disease; Young Adult; MEK inhibitor; Neurofibromatosis type 1; Neuropsychological profile; Trametinib
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-024-04624-3

Purpose
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.
Methods
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.
Results
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.
Conclusion
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.