Related Experiment Video
Updated: Jun 7, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis
Darcy A Krueger1, Marguerite M Care, Katherine Holland
1Department of Pediatrics, Tuberous Sclerosis Clinic, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Background:
Neurosurgical resection is the standard treatment for subependymal giant-cell astrocytomas in patients with the tuberous sclerosis complex. An alternative may be the use of everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in the tuberous sclerosis complex.
Methods:
Patients 3 years of age or older with serial growth of subependymal giant-cell astrocytomas were eligible for this open-label study. The primary efficacy end point was the change in volume of subependymal giant-cell astrocytomas between baseline and 6 months. We gave everolimus orally, at a dose of 3.0 mg per square meter of body-surface area, to achieve a trough concentration of 5 to 15 ng per milliliter.
Results:
We enrolled 28 patients. Everolimus therapy was associated with a clinically meaningful reduction in volume of the primary subependymal giant-cell astrocytoma, as assessed on independent central review (P<0.001 for baseline vs. 6 months), with a reduction of at least 30% in 21 patients (75%) and at least 50% in 9 patients (32%). Marked reductions were seen within 3 months and were sustained. There were no new lesions, worsening hydrocephalus, evidence of increased intracranial pressure, or necessity for surgical resection or other therapy for subependymal giant-cell astrocytoma. Of the 16 patients for whom 24-hour video electroencephalography data were available, seizure frequency for the 6-month study period (vs. the previous 6-month period) decreased in 9, did not change in 6, and increased in 1 (median change, -1 seizure; P=0.02). The mean (±SD) score on the validated Quality-of-Life in Childhood Epilepsy questionnaire (on which scores can range from 0 to 100, with higher scores indicating a better quality of life) was improved at 3 months (63.4±12.4) and 6 months (62.1±14.2) over the baseline score (57.8±14.0). Single cases of grade 3 treatment-related sinusitis, pneumonia, viral bronchitis, tooth infection, stomatitis, and leukopenia were reported.
Conclusions:
Everolimus therapy was associated with marked reduction in the volume of subependymal giant-cell astrocytomas and seizure frequency and may be a potential alternative to neurosurgical resection in some cases, though long-term studies are needed. (Funded by Novartis; ClinicalTrials.gov number, NCT00411619.).
Insights
Everolimus significantly reduced subependymal giant-cell astrocytoma volume and seizure frequency in tuberous sclerosis complex patients. This mTOR inhibitor shows promise as an alternative to surgery for these brain tumors.
Area of Science:
- Neuro-oncology
- Pharmacology
Background:
- Subependymal giant-cell astrocytomas (SEGAs) are common in tuberous sclerosis complex (TSC).
- Neurosurgical resection is the standard treatment for symptomatic SEGAs.
- Everolimus, an mTOR inhibitor, targets a pathway dysregulated in TSC.
Purpose of the Study:
- To evaluate the efficacy of everolimus in reducing SEGA volume.
- To assess the impact of everolimus on seizure frequency and quality of life.
- To determine if everolimus is a viable alternative to surgery for SEGAs.
Main Methods:
- Open-label study of patients aged 3+ with growing SEGAs.
- Oral everolimus administered at 3.0 mg/m² to achieve trough concentrations of 5-15 ng/mL.
- Primary endpoint: change in SEGA volume at 6 months; secondary endpoints included seizure frequency and quality of life.
Main Results:
- 28 patients enrolled; 75% (21/28) achieved ≥30% SEGA volume reduction, 32% (9/28) achieved ≥50% reduction.
- Seizure frequency decreased in 9/16 patients with available data (median change -1 seizure).
- Quality of Life in Childhood Epilepsy scores improved significantly at 3 and 6 months.
Conclusions:
- Everolimus therapy led to significant SEGA volume reduction and decreased seizure frequency.
- Everolimus represents a potential alternative to neurosurgical resection for SEGAs in TSC patients.
- Long-term efficacy and safety data are required for definitive conclusions.
