A POETIC Phase II study of continuous oral everolimus in recurrent, radiographically progressive pediatric low-grade glioma Journal Article
| Authors: | Wright, K. D.; Yao, X.; London, W. B.; Kao, P. C.; Gore, L.; Hunger, S.; Geyer, R.; Cohen, K. J.; Allen, J. C.; Katzenstein, H. M.; Smith, A.; Boklan, J.; Nazemi, K.; Trippett, T.; Karajannis, M.; Herzog, C.; Destefano, J.; Direnzo, J.; Pietrantonio, J.; Greenspan, L.; Cassidy, D.; Schissel, D.; Perentesis, J.; Basu, M.; Mizuno, T.; Vinks, A. A.; Prabhu, S. P.; Chi, S. N.; Kieran, M. W. |
| Article Title: | A POETIC Phase II study of continuous oral everolimus in recurrent, radiographically progressive pediatric low-grade glioma |
| Abstract: | 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. © 2020 Wiley Periodicals LLC |
| Keywords: | clinical trial; brain tumor; everolimus; mtor; phase 2; low-grade glioma |
| Journal Title: | Pediatric Blood and Cancer |
| Volume: | 68 |
| Issue: | 2 |
| ISSN: | 1545-5009 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2021-02-01 |
| Start Page: | e28787 |
| Language: | English |
| DOI: | 10.1002/pbc.28787 |
| PUBMED: | 33140540 |
| PROVIDER: | scopus |
| PMCID: | PMC9161236 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 January 2021 -- Source: Scopus |
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