Journal of Neuro-Oncology

, Volume 140, Issue 2, pp 435–444 | Cite as

Trametinib for progressive pediatric low-grade gliomas

  • Maria Kondyli
  • Valérie Larouche
  • Christine Saint-Martin
  • Benjamin Ellezam
  • Lauranne Pouliot
  • Daniel Sinnett
  • Geneviève Legault
  • Louis Crevier
  • Alex Weil
  • Jean-Pierre Farmer
  • Nada Jabado
  • Sébastien PerreaultEmail author
Clinical Study



Pediatric pilocytic astrocytomas (PAs) are low grade gliomas and the most common brain tumors in children. They often represent a therapeutic challenge when incompletely resected as they can recur and progress despite the use of several lines of chemotherapeutic agents or even radiation therapy. Genetic alterations leading to activation of the mitogen-activated-protein-kinase pathway are a hallmark of this disease and offer an interesting therapeutic alternative through the use of targeted inhibitors.


Here, we describe six children with sporadic PA who were treated with trametinib, a MEK inhibitor, following progression under conventional therapies. Retrospective chart review was performed.


The median age at diagnosis was 2.3 years (y) old [range 11 months (m)–8.5 y old]. KIAA1549-BRAF fusion was identified in five cases, and hotspot FGFR1/NF1/PTPN11 mutations in one. All patients received at least one previous line of chemotherapy (range 1–4). The median time on treatment was 11 m (range 4–20). Overall, we observed two partial responses and three minor responses as best response; three of these patients are still on therapy. Treatment was discontinued in the patient with progressive disease. The most frequent toxicities were minor to moderately severe skin rash and gastro-intestinal symptoms. Two patients had dose reduction due to skin toxicity. Quality of life was excellent with decreased hospital visits and a close to normal life.


Trametinib appears to be a suitable option for refractory pediatric low-grade glioma and warrants further investigations in case of progression.


Trametinib MEK inhibitor Low grade glioma Pilocytic astrocytoma Children 






Carbo/VP16 IA

Intra-arterial carboplatin and etoposide






Gross total resection








Minor response




Pilocytic astrocytoma


Progressive disease


Partial response


Stable disease


Subtotal resection




Thioguanine, procarbazine, CCNU, vincristine




World Health Organization







We would like to acknowledge the generous financial support of the Westmount Old Timers which made this study possible.


This study was funded by a grant from the Westmount Old Timers.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Maria Kondyli
    • 1
  • Valérie Larouche
    • 2
  • Christine Saint-Martin
    • 3
  • Benjamin Ellezam
    • 4
  • Lauranne Pouliot
    • 1
  • Daniel Sinnett
    • 5
  • Geneviève Legault
    • 6
  • Louis Crevier
    • 7
  • Alex Weil
    • 8
  • Jean-Pierre Farmer
    • 9
  • Nada Jabado
    • 6
  • Sébastien Perreault
    • 10
    Email author
  1. 1.Division of Hemato-Oncology, Department of Pediatrics, CHU Sainte-JustineUniversité de MontréalMontrealCanada
  2. 2.Division of Hemato-Oncology, Department of PediatricsCentre Hospitalier Universitaire de Québec-Université LavalQuebecCanada
  3. 3.Department of Radiology, McGill University Health CenterMontreal Children’s HospitalMontrealCanada
  4. 4.Department of Pathology, CHU Sainte-JustineUniversité de MontréalMontrealCanada
  5. 5.Hematology-Oncology Research Center, Department of Pediatrics, CHU Sainte-JustineUniversité de MontréalMontrealCanada
  6. 6.Division of Hemato-Oncology, Department of Pediatrics, McGill University Health CenterMontreal Children’s HospitalMontrealCanada
  7. 7.Division of Neurosurgery, Department of SurgeryCentre Hospitalier Universitaire de Québec-Université LavalQuebecCanada
  8. 8.Division of Neurosurgery, Department of Surgery, CHU Sainte-JustineUniversité de MontréalMontrealCanada
  9. 9.Division of Neurosurgery, Department of Pediatric SurgeryMcGill University Health CenterMontrealCanada
  10. 10.Division of Child Neurology, Department of Pediatrics, CHU Sainte-JustineUniversité de MontréalMontrealCanada

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