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Trametinib for progressive pediatric low-grade gliomas

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

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.

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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

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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.

Author information

Authors and Affiliations

  1. Division of Hemato-Oncology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada

    Maria Kondyli & Lauranne Pouliot

  2. Division of Hemato-Oncology, Department of Pediatrics, Centre Hospitalier Universitaire de Québec-Université Laval, Quebec, QC, Canada

    Valérie Larouche

  3. Department of Radiology, McGill University Health Center, Montreal Children’s Hospital, Montreal, QC, Canada

    Christine Saint-Martin

  4. Department of Pathology, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada

    Benjamin Ellezam

  5. Hematology-Oncology Research Center, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada

    Daniel Sinnett

  6. Division of Hemato-Oncology, Department of Pediatrics, McGill University Health Center, Montreal Children’s Hospital, Montreal, QC, Canada

    Geneviève Legault & Nada Jabado

  7. Division of Neurosurgery, Department of Surgery, Centre Hospitalier Universitaire de Québec-Université Laval, Quebec, QC, Canada

    Louis Crevier

  8. Division of Neurosurgery, Department of Surgery, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada

    Alex Weil

  9. Division of Neurosurgery, Department of Pediatric Surgery, McGill University Health Center, Montreal, QC, Canada

    Jean-Pierre Farmer

  10. Division of Child Neurology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, QC, H3T 1C5, Canada

    Sébastien Perreault

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  1. Maria Kondyli
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  2. Valérie Larouche
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  3. Christine Saint-Martin
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Correspondence to Sébastien Perreault.

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Kondyli, M., Larouche, V., Saint-Martin, C. et al. Trametinib for progressive pediatric low-grade gliomas. J Neurooncol 140, 435–444 (2018). https://doi.org/10.1007/s11060-018-2971-9

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