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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 Perreault
Clinical Study

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusion

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

Keywords

Trametinib MEK inhibitor Low grade glioma Pilocytic astrocytoma Children 

Abbreviations

Bx

Biopsy

Carbo–VCR

Carboplatin–vincristine

Carbo/VP16 IA

Intra-arterial carboplatin and etoposide

GBM

Glioblastoma

F

Female

GTR

Gross total resection

LND

Lenalidomide

M

Male

m

Months

MR

Minor response

Oxa

Oxaliplatin

PA

Pilocytic astrocytoma

PD

Progressive disease

PR

Partial response

STD

Stable disease

STR

Subtotal resection

TMZ

Temozolomide

TPCV

Thioguanine, procarbazine, CCNU, vincristine

VBL

Vinblastine

WHO

World Health Organization

XRT

Radiotherapy

y

Years

Notes

Acknowledgements

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

Funding

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
  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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