Trametinib for progressive pediatric low-grade gliomas

J Neurooncol. 2018 Nov;140(2):435-444. doi: 10.1007/s11060-018-2971-9. Epub 2018 Aug 10.


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: Children; Low grade glioma; MEK inhibitor; Pilocytic astrocytoma; Trametinib.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Astrocytoma / diagnostic imaging
  • Astrocytoma / drug therapy*
  • Astrocytoma / genetics
  • Astrocytoma / physiopathology
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / physiopathology
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Humans
  • Infant
  • Male
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridones / adverse effects
  • Pyridones / therapeutic use*
  • Pyrimidinones / adverse effects
  • Pyrimidinones / therapeutic use*
  • Retreatment
  • Retrospective Studies


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyridones
  • Pyrimidinones
  • trametinib