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Trametinib for progressive pediatric low-grade gliomas
Maria Kondyli1, Valérie Larouche2, Christine Saint-Martin3
1Division of Hemato-Oncology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada.
Journal of Neuro-Oncology
|August 12, 2018
Summary
Trametinib shows promise for treating pediatric pilocytic astrocytomas (PAs) that resist conventional therapies. This MEK inhibitor demonstrated positive responses and improved quality of life in children with refractory low-grade gliomas.
Area of Science:
- Pediatric oncology
- Neuro-oncology
- Molecular targeted therapy
Background:
- Pediatric pilocytic astrocytomas (PAs) are common pediatric brain tumors, often posing treatment challenges when incompletely resected.
- Genetic alterations activating the MAPK pathway are characteristic of PAs, suggesting targeted inhibitors as a therapeutic strategy.
Observation:
- Six children with sporadic PAs, refractory to conventional therapies, were treated with trametinib, a MEK inhibitor.
- Genetic analysis revealed KIAA1549-BRAF fusion in five patients and mutations in FGFR1/NF1/PTPN11 in one.
Findings:
- Trametinib treatment resulted in two partial and three minor responses, with three patients continuing therapy.
- The most common toxicities included skin rash and gastrointestinal symptoms; quality of life remained high.
Implications:
- Trametinib represents a potential therapeutic option for pediatric low-grade gliomas that are refractory to standard treatments.
- Further investigation of trametinib is warranted for progressive pediatric low-grade gliomas.
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