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

DuBois SG, Krailo MD, Glade-Bender J, Buxton A, Laack N, Randall RL, Chen HX, Seibel NL, Boron M, Terezakis S, Hill-Kayser C, Hayes A, Reid JM, Teot L, Rakheja D, Womer R, Arndt C, Lessnick SL, Crompton BD, Kolb EA, Daldrup-Link H, Eutsler E, Reed DR, Janeway KA, Gorlick RG. 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. J Clin Oncol. 2023 Apr 10;41(11):2098-2107. doi: 10.1200/JCO.22.01815. Epub 2023 Jan 20. PubMed PMID: 36669140; PubMed Central PMCID: PMC10082251.

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. Patients 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.