Phase II study of everolimus for recurrent or progressive pediatric ependymoma

Area of Science:

• Pediatric Oncology
• Neuro-Oncology
• Molecular Targeted Therapy

Background:

• Preclinical studies indicate the mTOR pathway is a potential therapeutic target for childhood ependymoma.
• Ependymoma is a primary brain tumor affecting children, with specific subtypes like posterior fossa A (PF-A) posing treatment challenges.

Purpose of the Study:

• To evaluate the efficacy of everolimus, an mTOR inhibitor, in children with recurrent or progressive ependymomas.
• To test the hypothesis that inhibiting the mTOR pathway leads to tumor response in pediatric ependymoma patients.

Main Methods:

• A phase II clinical trial (NCT02155920) administered single-agent everolimus to pediatric patients.
• Eleven subjects with recurrent/progressive ependymomas (median age 8 years) received oral everolimus (4.5 mg/m²/day).
• Treatment involved dose titration to achieve serum trough levels of 5-15 ng/ml over 28-day cycles.

Main Results:

• Everolimus was generally well-tolerated, with most adverse events being grade 1-2, except for one case of grade 3 pneumonia.
• No objective tumor responses were observed in any of the participating subjects.
• All subjects experienced tumor progression and discontinued therapy after a median of 2 cycles.

Conclusions:

• Single-agent everolimus demonstrated no significant activity in children with recurrent or progressive PF-A ependymoma.
• The mTOR pathway may not be a viable therapeutic target for this specific patient population.
• Alternative treatment strategies are necessary for children diagnosed with recurrent or progressive ependymoma.