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Targeted therapy
Source: Childhood Astrocytomas, Other Gliomas, and Glioneuronal/Neuronal Tumors Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 14, 2025 · Captured 2026-09-09.
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The U.S. Food and Drug Administration (FDA) approved the combination of trametinib (MEK inhibitor) plus dabrafenib (BRAF inhibitor) for the treatment of pediatric patients aged 1 year and older with low-grade gliomas and a BRAF V600E variant who require systemic therapy. The approval was based on a randomized clinical trial that compared the dabrafenib-plus-trametinib combination with the carboplatin-plus-vincristine combination. The median age of enrolled patients was 9.5 years, and the most common histological subtypes were ganglioglioma (about 25%) and pilocytic astrocytoma (about 30%). Patients were randomly assigned in a 2-to-1 ratio, with 73 receiving dabrafenib plus trametinib and 37 receiving carboplatin plus vincristine. Patients received dabrafenib and trametinib until loss of clinical benefit or until unacceptable toxicity, and the carboplatin-plus-vincristine combination was given as a 10-week induction course, followed by eight 6-week cycles of therapy.[67]
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The objective response rate was assessed by independent review using Response Assessment in Neuro-Oncology (RANO) 2017 response criteria for low-grade glioma that employ T2-fluid attenuated inversion recovery (FLAIR) rather than contrast enhancement.
Patients randomly assigned to dabrafenib plus trametinib had a significantly higher objective response rate compared with patients who received carboplatin plus vincristine (47% vs. 11%). An additional 41% of patients in each treatment group had stable disease.
Patients randomly assigned to dabrafenib plus trametinib had a significantly longer PFS compared with patients who received carboplatin plus vincristine (20.1 months vs. 7.4 months).
Grade 3 or higher adverse events were more common in patients who received carboplatin plus vincristine compared with patients who received dabrafenib plus trametinib (94% vs. 47%).
IDH inhibitors are being studied for the treatment of patients with IDH-altered low-grade and high-grade gliomas. One agent, vorasidenib, has shown preliminary evidence of activity in delaying the time to progression when compared with placebo in newly diagnosed adults with IDH1- or IDH2-altered low-grade gliomas.[68] The FDA approved vorasidenib for adult and pediatric patients aged 12 years and older with grade 2 astrocytomas or oligodendrogliomas and a susceptible IDH1 or IDH2 variant after surgery, which includes biopsy, subtotal resection, or gross-total resection.
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For children with tuberous sclerosis (TS) and symptomatic subependymal giant cell astrocytomas (SEGAs), agents that inhibit mammalian target of rapamycin (mTOR) (e.g., everolimus and sirolimus) have been studied.
Evidence (treatment of SEGA with an mTOR inhibitor):
Small series have shown significant reductions in the size of these tumors after administration of everolimus or sirolimus, often eliminating the need for surgery.[69]; [70][Level of evidence B4]; [71][Level of evidence C3]; [72][Level of evidence C1]
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A multicenter, phase III, placebo-controlled trial of 117 patients confirmed these earlier findings.[73][Level of evidence B3]
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A multicenter, phase III, placebo-controlled trial of 117 patients confirmed these earlier findings.[73][Level of evidence B3]
Thirty-five percent of the patients in the everolimus group had at least a 50% reduction in the size of the SEGA, versus no reduction in the placebo group.
In a study of patients who were treated with everolimus for 5 years, the following results were observed:[74]
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In a study of patients who were treated with everolimus for 5 years, the following results were observed:[74]
A reduction in the size of the mass was observed in about 50% of patients; in many cases, the reduction was sustained.
In a study of patients who were treated with everolimus for 5 years, the following results were observed:[74]
These patients also had a reduction in seizure frequency.
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