1. Randomized Phase III Trial of Ganitumab With Interval-Compressed Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma: A Report From the Childrens Oncology Group.
- Author
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Chen, Helen, Seibel, Nita, Boron, Matthew, Terezakis, Stephanie, Hill-Kayser, Christine, Hayes, Andrea, Reid, Joel, Teot, Lisa, Rakheja, Dinesh, Womer, Richard, Arndt, Carola, Lessnick, Stephen, Crompton, Brian, Kolb, E, Daldrup-Link, Heike, Eutsler, Eric, Reed, Damon, Janeway, Katherine, Gorlick, Richard, DuBois, Steven, Krailo, Mark, Glade-Bender, Julia, Buxton, Allen, Laack, Nadia, and Randall, R
- Subjects
Humans ,Child ,Sarcoma ,Ewing ,Neoplasm Recurrence ,Local ,Bone Neoplasms ,Antibodies ,Monoclonal ,Humanized ,Cyclophosphamide ,Etoposide ,Antineoplastic Combined Chemotherapy Protocols ,Doxorubicin ,Vincristine ,Antibodies ,Monoclonal ,Disease-Free Survival - 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 Childrens 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. METHODS: 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. RESULTS: Two 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. CONCLUSION: Ganitumab 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.
- Published
- 2023