TY - JOUR
T1 - Single-agent erlotinib versus oral etoposide in patients with recurrent or refractory pediatric ependymoma
T2 - a randomized open-label study
AU - Jakacki, Regina I.
AU - Foley, Margaret A.
AU - Horan, Julie
AU - Wang, Jiuzhou
AU - Kieran, Mark W.
AU - Bowers, Daniel C.
AU - Bouffet, Eric
AU - Zacharoulis, Stergios
AU - Gill, Stan C.
N1 - Funding Information:
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.
Publisher Copyright:
© 2016, Springer Science+Business Media New York.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - EGFR
KW - Ependymoma
KW - Epidermal growth factor receptor
KW - Erlotinib
KW - Etoposide
KW - Pediatrics
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U2 - 10.1007/s11060-016-2155-4
DO - 10.1007/s11060-016-2155-4
M3 - Article
C2 - 27287856
AN - SCOPUS:84973659348
SN - 0167-594X
VL - 129
SP - 131
EP - 138
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 1
ER -