Single-agent erlotinib versus oral etoposide in patients with recurrent or refractory pediatric ependymoma: a randomized open-label study
- 10 June 2016
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Neuro-Oncology
- Vol. 129 (1), 131-138
- https://doi.org/10.1007/s11060-016-2155-4
Abstract
Overexpression of human epidermal growth factor receptor (HER/EGFR) is associated with various tumors, including ependymomas. To investigate whether EGFR inhibition was of benefit in pediatric patients with recurrent ependymoma, a multi-center, randomized, open-label, phase 2 study of oral erlotinib versus oral etoposide was undertaken. Twenty-five patients were randomized to receive erlotinib 85 mg/m2 daily or etoposide 50 mg/m2/day for 21 consecutive days followed by a 7-day rest period. Courses were repeated every 28 days. In the erlotinib arm, no patient achieved a complete, partial, or minor response, and only 2 (15.4 %) patients showed stable disease as their best response. In the etoposide arm, 2 patients (16.7 %) demonstrated partial responses, 1 (8.3 %) patient demonstrated a minor response, and 2 (16.7 %) showed prolonged stable disease, for a prolonged disease control rate of 41.7 %. Three patients received at least nine cycles of etoposide (range 9–24 cycles) before discontinuing at the request of the physician and/or family. Four patients who failed etoposide in this study received erlotinib in a companion single arm study; none had a response. The futility criteria were met at the second interim analysis, and both studies were discontinued. Pharmacokinetics of erlotinib were similar to previous observations in pediatric patients. Overall, erlotinib was well tolerated and safety was consistent with its established profile in adults. The overall risk–benefit profile does not support the use of erlotinib in pediatric patients with recurrent ependymoma, whereas single-agent etoposide appears to have efficacy in a subset of patients.Funding Information
- Astellas Pharma Global Development
This publication has 18 references indexed in Scilit:
- Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic ImplicationsMolecular Biology International, 2014
- A phase II trial of a multi‐agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancerPediatric Blood & Cancer, 2013
- The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancerMolecular and Clinical Oncology, 2013
- Survival Benefit for Pediatric Patients With Recurrent Ependymoma Treated With ReirradiationInternational Journal of Radiation Oncology*Biology*Physics, 2012
- Both location and age predict survival in ependymoma: A SEER studyPediatric Blood & Cancer, 2008
- Pediatric Phase I and Pharmacokinetic Study of Erlotinib Followed by the Combination of Erlotinib and Temozolomide: A Children's Oncology Group Phase I Consortium StudyJournal of Clinical Oncology, 2008
- Identification of Gains on 1q and Epidermal Growth Factor Receptor Overexpression as Independent Prognostic Markers in Intracranial EpendymomaClinical Cancer Research, 2006
- A Feasibility Trial of Antiangiogenic (Metronomic) Chemotherapy in Pediatric Patients With Recurrent or Progressive CancerJournal of Pediatric Hematology/Oncology, 2005
- Treatment With Oral Etoposide for Childhood Recurrent EpendymomasJournal of Pediatric Hematology/Oncology, 2005
- Recurrent intracranial ependymoma in children: salvage therapy with oral etoposidePediatric Neurology, 2001