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Trametinib-based Treatment of Pediatric CNS Tumors: A Single Institutional Experience
Megan R Paul1,2, Katherine C Pehlivan1, Mehrzad Milburn2
1Department of Neurosciences, University of California and Rady Children's Hospital.
Abstract:
MEK inhibitors are an emerging therapy with increasing use in mitogen-activated protein kinase-driven central nervous system (CNS) tumors. There is limited data regarding efficacy and toxicity in pediatric patients. We report our clinical experience with trametinib-based therapy for the treatment of 14 consecutive pediatric patients with recurrent low-grade glioma (N=11) or high-grade CNS tumors (N=3) with MAP kinase pathway mutations. Patients received trametinib as monotherapy (N=9) or in combination (N=5) with another antineoplastic agent. Nine patients (64%) were progression free during treatment. Five patients showed a partial response, while 4 had stable disease. Two patients (14%) progressed on therapy. All partial responses were in patients with low-grade tumors. The remaining 3 patients were not evaluable due to toxicity limiting duration of therapy. Two of 3 patients with low-grade glioma with leptomeningeal dissemination showed radiographic treatment response. Five patients reported improved clinical symptoms while on trametinib. Adverse events on trametinib-based therapy included dermatologic, mouth sores, fever, gastrointestinal, infection, neutropenia, headache, and fatigue, and were more common in patients using combination therapy. Trametinib-based therapy demonstrated signals of efficacy in our single institutional cohort of pediatric patients with mitogen-activated protein kinase-driven CNS tumors. Our observations need to be confirmed in a clinical trial setting.
Insights
Trametinib shows promise for pediatric central nervous system (CNS) tumors driven by MAP kinase pathway mutations. While 64% of patients remained progression-free, further clinical trials are needed to confirm efficacy and safety.
Area of Science:
- Pediatric Oncology
- Neuro-oncology
- Molecular Targeted Therapy
Background:
- Mitogen-activated protein kinase (MAPK) pathway mutations are implicated in central nervous system (CNS) tumors.
- MEK inhibitors represent an emerging therapeutic class for these tumors.
- Limited data exists on MEK inhibitor efficacy and toxicity in pediatric populations.
Purpose of the Study:
- To evaluate the clinical experience of trametinib-based therapy in pediatric patients with MAPK-driven CNS tumors.
- To assess the efficacy and toxicity of trametinib in this cohort.
Main Methods:
- Retrospective analysis of 14 pediatric patients with recurrent low-grade or high-grade CNS tumors harboring MAPK pathway mutations.
- Patients received trametinib as monotherapy or in combination with other agents.
- Clinical outcomes including progression-free survival, response rates, and adverse events were recorded.
Main Results:
- 64% of patients (9/14) achieved progression-free status.
- Partial responses were observed in 5 patients, all with low-grade gliomas.
- Adverse events were manageable and included dermatologic toxicities, mucositis, and fatigue, with higher incidence in combination therapy.
Conclusions:
- Trametinib-based therapy demonstrates preliminary efficacy signals in pediatric MAPK-driven CNS tumors.
- Responses were noted in low-grade gliomas, including those with leptomeningeal dissemination.
- Further investigation in clinical trials is warranted to validate these findings.
