A POETIC Phase II study of continuous oral everolimus in recurrent, radiographically progressive pediatric low-grade glioma

Karen D. Wright, Xiaopan Yao, Wendy B. London, Pei Chi Kao, Lia Gore, Stephen Hunger, Russ Geyer, Kenneth J. Cohen, Jeffrey C. Allen, Howard M. Katzenstein, Amy Smith, Jessica Boklan, Kellie Nazemi, Tanya Trippett, Matthias Karajannis, Cynthia Herzog, Joseph Destefano, Jennifer Direnzo, Jay Pietrantonio, Lianne GreenspanDanielle Cassidy, Debra Schissel, John Perentesis, Mitali Basu, Tomoyuki Mizuno, Alexander A. Vinks, Sanjay P. Prabhu, Susan N. Chi, Mark W. Kieran

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15 Scopus citations


Background: To evaluate efficacy, pharmacokinetics (PK) and pharmacodynamics of single-agent everolimus in pediatric patients with radiographically progressive low-grade glioma (LGG). Methods: Everolimus was administered at 5 mg/m2 once daily as a tablet or liquid for a planned 48-week duration or until unacceptable toxicity or disease progression. Patients with neurofibromatosis type 1 were excluded. PK and pharmacodynamic endpoints were assessed in consenting patients. Results: Twenty-three eligible patients (median age 9.2 years) were enrolled. All patients received prior chemotherapy (median number of prior regimens two) and/or radiotherapy (two patients). By week 48, two patients had a partial response, 10 stable disease, and 11 clinical or radiographic progression; two discontinued study prior to 1 year (toxicity: 1, physician determination: 1). With a median follow up of 1.8 years (range 0.2-6.7 years), the 2-, 3-, and 5-year progression-free survivals (PFS) were 39 ± 11%, 26 ± 11%, and 26 ± 11%, respectively; two patients died of disease. The 2-, 3-, and 5-year overall survival (OS) were all 93 ± 6%. Grade 1 and 2 toxicities predominated; two definitively related grade 3 toxicities (mucositis and neutropenia) occurred. Grade 4 elevation of liver enzymes was possibly related in one patient. Predose blood levels showed substantial variability between patients with 45.5% below and 18.2% above the target range of 5-15 ng/mL. Pharmacodynamic analysis demonstrated significant inhibition in phospho-S6, 4E-BP1, and modulation of c-Myc expression. Conclusion: Daily oral everolimus provides a well-tolerated, alternative treatment for multiple recurrent, radiographically progressive pediatric LGG. Based on these results, everolimus is being investigated further for this patient population.

Original languageEnglish
Article numbere28787
JournalPediatric Blood and Cancer
Issue number2
StatePublished - Feb 2021
Externally publishedYes


  • brain tumor
  • clinical trial
  • everolimus
  • low-grade glioma
  • mTOR
  • phase 2


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