Randomized Phase III Trial of Ganitumab with Interval-Compressed Chemotherapy for Patients with Newly Diagnosed Metastatic Ewing Sarcoma: A Report from the Children's Oncology Group

Steven G. DuBois, Mark D. Krailo, Julia Glade-Bender, Allen Buxton, Nadia Laack, R. Lor Randall, Helen X. Chen, Nita L. Seibel, Matthew Boron, Stephanie Terezakis, Christine Hill-Kayser, Andrea Hayes, Joel M. Reid, Lisa Teot, Dinesh Rakheja, Richard Womer, Carola Arndt, Stephen L. Lessnick, Brian D. Crompton, E. Anders KolbHeike Daldrup-Link, Eric Eutsler, Damon R. Reed, Katherine A. Janeway, Richard G. Gorlick

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17 Scopus citations

Abstract

PURPOSE Monoclonal antibodies directed against insulin-like growth factor-1 receptor (IGF-1R) have shown activity in patients with relapsed Ewing sarcoma. The primary objective of Children's Oncology Group trial AEWS1221 was to determine if the addition of the IGF-1R monoclonal antibody ganitumab to interval-compressed chemotherapy improves event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma.METHODSPatients were randomly assigned 1:1 at enrollment to standard arm (interval-compressed vincristine/doxorubicin/cyclophosphamide alternating once every 2 weeks with ifosfamide/etoposide = VDC/IE) or to experimental arm (VDC/IE with ganitumab at cycle starts and as monotherapy once every 3 weeks for 6 months after conventional therapy). A planned sample size of 300 patients was projected to provide 81% power to detect an EFS hazard ratio of 0.67 or smaller for the experimental arm compared with the standard arm with a one-sided α of.025.RESULTSTwo hundred ninety-eight eligible patients enrolled (148 in standard arm; 150 in experimental arm). The 3-year EFS estimates were 37.4% (95% CI, 29.3 to 45.5) for the standard arm and 39.1% (95% CI, 31.3 to 46.7) for the experimental arm (stratified EFS-event hazard ratio for experimental arm 1.00; 95% CI, 0.76 to 1.33; 1-sided, P =.50). The 3-year overall survival estimates were 59.5% (95% CI, 50.8 to 67.3) for the standard arm and 56.7% (95% CI, 48.3 to 64.2) for the experimental arm. More cases of pneumonitis after radiation involving thoracic fields and nominally higher rates of febrile neutropenia and ALT elevation were reported on the experimental arm.CONCLUSIONGanitumab added to interval-compressed chemotherapy did not significantly reduce the risk of EFS event in patients with newly diagnosed metastatic Ewing sarcoma, with outcomes similar to prior trials without IGF-1R inhibition or interval compression. The addition of ganitumab may be associated with increased toxicity.

Original languageEnglish (US)
Pages (from-to)2098-2107
Number of pages10
JournalJournal of Clinical Oncology
Volume41
Issue number11
DOIs
StatePublished - Apr 10 2023

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Publisher Copyright:
© American Society of Clinical Oncology.

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