TY - JOUR
T1 - Randomized Phase III Trial of Ganitumab with Interval-Compressed Chemotherapy for Patients with Newly Diagnosed Metastatic Ewing Sarcoma
T2 - A Report from the Children's Oncology Group
AU - DuBois, Steven G.
AU - Krailo, Mark D.
AU - Glade-Bender, Julia
AU - Buxton, Allen
AU - Laack, Nadia
AU - Randall, R. Lor
AU - Chen, Helen X.
AU - Seibel, Nita L.
AU - Boron, Matthew
AU - Terezakis, Stephanie
AU - Hill-Kayser, Christine
AU - Hayes, Andrea
AU - Reid, Joel M.
AU - Teot, Lisa
AU - Rakheja, Dinesh
AU - Womer, Richard
AU - Arndt, Carola
AU - Lessnick, Stephen L.
AU - Crompton, Brian D.
AU - Kolb, E. Anders
AU - Daldrup-Link, Heike
AU - Eutsler, Eric
AU - Reed, Damon R.
AU - Janeway, Katherine A.
AU - Gorlick, Richard G.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/4/10
Y1 - 2023/4/10
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.22.01815
DO - 10.1200/JCO.22.01815
M3 - Article
C2 - 36669140
AN - SCOPUS:85151535606
SN - 0732-183X
VL - 41
SP - 2098
EP - 2107
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -