Trametinib for the treatment of recurrent/progressive pediatric low-grade glioma

J Neurooncol. 2020 Sep;149(2):253-262. doi: 10.1007/s11060-020-03592-8. Epub 2020 Aug 11.


Purpose: Pediatric low-grade gliomas (pLGGs) are the most common CNS tumor of childhood and comprise a heterogenous group of tumors. Children with progressive pLGG often require numerous treatment modalities including surgery, chemotherapy, rarely radiation therapy and, more recently, molecularly targeted therapy. We describe our institutional experience using the MEK inhibitor, trametinib, for recurrent/progressive pLGGs.

Methods: We performed a retrospective, IRB-approved, chart review of all pediatric patients treated with trametinib for recurrent/progressive pLGGs at Dana-Farber/Boston Children's Cancer and Blood Disorder Center between 2016 and 2018.

Results: Eleven patients were identified, of which 10 were evaluable for response. Median age at commencement of trametinib treatment was 14.7 years (range 7.3-25.9 years). Tumor molecular status included KIAA1549-BRAF fusion (n = 4), NF1 mutation (n = 4), FGFR mutation (n = 1) and CDKN2A loss (n = 1). Median number of prior treatment regimens was 5 (range 1-12). Median duration of treatment with trametinib was 19.2 months (range 3.8-29.8 months). Based on modified RANO criteria, best responses included partial (n = 2), minor response (n = 2) and stable disease (n = 6). Two patients remain on therapy (29.8 and 25.9 months, respectively). The most common toxicities attributable to trametinib were rash, fatigue and gastrointestinal disturbance. Five patients required dose reduction for toxicities. Two patients experienced significant intracranial hemorrhage (ICH) while on trametinib. While it is unclear whether ICH was directly attributable to trametinib, therapy was discontinued.

Conclusion: Trametinib appears to be an effective treatment for patients with recurrent/progressive pLGG. The toxicities of this therapy warrant further investigation, with particular attention to the potential risk for intracranial hemorrhage. Early phase multi-institutional clinical trials are underway.

Keywords: Central nervous system neoplasms; Low-grade glioma; MAPK; MEK inhibitor; Pediatric; Trametinib.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Child
  • Female
  • Follow-Up Studies
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Male
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Pyridones / therapeutic use*
  • Pyrimidinones / therapeutic use*
  • Retrospective Studies
  • Young Adult


  • Antineoplastic Agents
  • Pyridones
  • Pyrimidinones
  • trametinib