Single-agent erlotinib versus oral etoposide in patients with recurrent or refractory pediatric ependymoma: a randomized open-label 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/m(2) daily or etoposide 50 mg/m(2)/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.
Children's Hospital of Pittsburgh, University of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA, 15224, USA. regina.jakacki@astrazeneca.com.|AstraZeneca, One Medimmune Way, Gaithersburg, MD, 20878, USA. regina.jakacki@astrazeneca.com.
Regina I
RI
Jakacki
Astellas Pharma Global Development, 1 Astellas Way, Northbrook, IL, 60062, USA.
Margaret A
MA
Foley
Novella Clinical, 4840 Pearl E Cir # 100, Boulder, CO, 80301, USA.
Julie
J
Horan
Astellas Pharma Global Development, 1 Astellas Way, Northbrook, IL, 60062, USA.
Jiuzhou
J
Wang
Pediatric Neuro-Oncology, Dana-Farber Cancer Institution, Boston Children's Hospital, 450 Brookline Ave., D-3154, Boston, MA, 02215, USA.
Mark W
MW
Kieran
Department of Pediatrics, University of Texas Southwestern Medical School, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.
Daniel C
DC
Bowers
The Hospital for Sick Kids, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Eric
E
Bouffet
The Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, UK.
Stergios
S
Zacharoulis
Astellas Pharma Global Development, 1 Astellas Way, Northbrook, IL, 60062, USA.
Stan C
SC
Gill
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004806:Ependymoma / Q000188:drug therapy*; D000069347:Erlotinib Hydrochloride / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000972:Antineoplastic Agents, Phytogenic; D047428:Protein Kinase Inhibitors; D005047:Etoposide; D000069347:Erlotinib Hydrochloride
EGFR; Ependymoma; Epidermal growth factor receptor; Erlotinib; Etoposide; Pediatrics