Related Experiment Video
Updated: Nov 9, 2025
Co-culture of Glutamatergic Neurons and Pediatric High-Grade Glioma Cells Into Microfluidic Devices to Assess Electrical Interactions
Published on: November 17, 2021
Targeted therapy for pediatric low-grade glioma
Juan Pablo Muñoz Pérez1, Jordi Muchart2, Vicente Santa-María López1,3
1Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain.
Purpose:
Pediatric low-grade gliomas are the most frequent brain tumors in children. The standard approach for symptomatic unresectable tumors is chemotherapy. Recently, key molecular alterations/pathways have been identified and targeted drugs developed and tested in clinical trials. We describe our institutional experience with MAPK pathway targeted therapy.
Methods:
We retrospectively reviewed the medical reports of 23 patients diagnosed with PLGG and treated with either trametinib or dabrafenib at Hospital Sant Joan de Dèu (Barcelona, Spain). Patients with neurofibromatosis were excluded. Objective response rate (ORR) and disease control rate (DCR) were determined using the Response Assessment in Pediatric Neuro-Oncology criteria in low-grade glioma. ORR was defined as the proportion of patients with the best overall response including complete remission (CR) or partial remission (PR). DCR was the sum of the CR, PR, and stable disease (SD) rates.
Results:
ORR with trametinib was 0% (95% CI, 0%-23.2%) and DCR was 78.6% (95% CI, 49.2%-95.3%). Eleven patients had SD and three patients presented PD. ORR with dabrafenib was 41.7% (95% CI, 16.5%-71.4%), including four CR and one patient with PR. DCR with dabrafenib was 100% (95% CI, 73.5%-100%); there were seven SD and none PD. Treatment was well tolerated. Only three patients, on trametinib, presented grade 3 adverse effects: leukocytoclastic vasculitis, cheilitis, and bone infection.
Conclusions:
Our experience adds to the growing data about the efficacy and tolerability of targeted therapy in patients with PLGG. When present, toxicity is mainly mild-moderate and transient. Ongoing prospective clinical trials are trying to address if its use should be advanced to first-line therapy.
Insights
Targeted therapy shows promise for pediatric low-grade gliomas (PLGG). Dabrafenib demonstrated higher objective response rates than trametinib, with both drugs generally well-tolerated in this study.
Area of Science:
- Pediatric Oncology
- Neuro-Oncology
- Molecular Targeted Therapy
Background:
- Pediatric low-grade gliomas (PLGG) are the most common pediatric brain tumors.
- Chemotherapy is the standard treatment for symptomatic, unresectable tumors.
- Advances in identifying molecular alterations have led to targeted drug development.
Purpose of the Study:
- To evaluate the institutional experience with MAPK pathway targeted therapy for pediatric low-grade gliomas.
- To assess the efficacy and tolerability of trametinib and dabrafenib in this patient population.
Main Methods:
- Retrospective review of 23 pediatric low-grade glioma patients treated with trametinib or dabrafenib.
- Exclusion of patients with neurofibromatosis.
- Assessment of Objective Response Rate (ORR) and Disease Control Rate (DCR) using RANO criteria.
Main Results:
- Trametinib: ORR 0%, DCR 78.6% (11 SD, 3 PD).
- Dabrafenib: ORR 41.7% (4 CR, 1 PR), DCR 100% (7 SD).
- Treatment was generally well-tolerated; Grade 3 adverse events were rare and associated with trametinib.
Conclusions:
- Targeted therapy demonstrates efficacy and tolerability in pediatric low-grade gliomas.
- Toxicity is typically mild-to-moderate and transient.
- Ongoing trials investigate the potential of targeted therapy as first-line treatment.
