Journal of Neuro-Oncology

, Volume 129, Issue 1, pp 131–138 | Cite as

Single-agent erlotinib versus oral etoposide in patients with recurrent or refractory pediatric ependymoma: a randomized open-label study

  • Regina I. Jakacki
  • Margaret A. Foley
  • Julie Horan
  • Jiuzhou Wang
  • Mark W. Kieran
  • Daniel C. Bowers
  • Eric Bouffet
  • Stergios Zacharoulis
  • Stan C. Gill
Clinical Study


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.


Ependymoma Epidermal growth factor receptor EGFR Pediatrics Etoposide Erlotinib 



The authors would like to acknowledge all of the investigators who participated in this study, the patients and their families.


This study was funded by Astellas Pharma, Inc. Medical writing support was provided by Tara N. Miller, PhD, and Sarah J. Knott, medical writers at Envision Scientific Solutions, and funded by Astellas.

Compliance with ethical standards

Conflict of interest

Regina I. Jakacki is now at Astra-Zeneca; Margaret A. Foley, Jiuzhou Wang, and Stan C. Gill are full-time employees of Astellas; Mark W. Kieran, Daniel C. Bowers, Eric Bouffet, and Stergios Zacharoulis have no conflicts to report. Julie Horan was an employee of OSI Pharmaceuticals, Inc. during the development of the protocol and Novella Clinical Inc. during the study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

11060_2016_2155_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 23 KB)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Regina I. Jakacki
    • 1
    • 8
  • Margaret A. Foley
    • 2
  • Julie Horan
    • 3
  • Jiuzhou Wang
    • 2
  • Mark W. Kieran
    • 4
  • Daniel C. Bowers
    • 5
  • Eric Bouffet
    • 6
  • Stergios Zacharoulis
    • 7
  • Stan C. Gill
    • 2
  1. 1.Children’s Hospital of PittsburghUniversity of PittsburghPittsburghUSA
  2. 2.Astellas Pharma Global DevelopmentNorthbrookUSA
  3. 3.Novella ClinicalBoulderUSA
  4. 4.Pediatric Neuro-OncologyDana–Farber Cancer Institution, Boston Children’s HospitalBostonUSA
  5. 5.Department of PediatricsUniversity of Texas Southwestern Medical SchoolDallasUSA
  6. 6.The Hospital for Sick KidsTorontoCanada
  7. 7.The Royal Marsden HospitalSuttonUK
  8. 8.AstraZenecaGaithersburgUSA

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