Adding ganitumab to standard chemotherapy does not provide a benefit for patients with metastatic Ewing sarcoma, according to research published in the Journal of Clinical Oncology.

In this phase 3 trial, the IGF-1R monoclonal antibody ganitumab did not improve event-free survival (EFS) or overall survival (OS) when added to standard chemotherapy.

The trial ( Identifier: NCT02306161) enrolled 298 patients who were younger than 50 years old and had newly diagnosed, metastatic Ewing sarcoma or primitive neuroectodermal tumor.

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The patients were randomly assigned to receive standard chemotherapy alone (n=148) or standard chemotherapy plus ganitumab (n=150). Chemotherapy consisted of interval-compressed vincristine plus doxorubicin and cyclophosphamide, alternating once every 2 weeks with ifosfamide and etoposide. Ganitumab was given at 18 mg/kg once at the start of cycles 1-6 and 10-14 for 14 cycles.

After the first 6 treatment cycles, patients underwent investigator’s choice of surgery, radiation, or surgery plus radiation for local control. After completing 14 cycles of chemotherapy (with or without ganitumab), patients received radiotherapy to metastatic sites. Surgical management of soft tissue metastasis was allowed as well. After that, patients in the experimental arm received ganitumab maintenance, given at 18 mg/kg once every 3 weeks for 6 months.

At the second interim analysis in March 2019, the data and safety monitoring committee recommended early closure of the trial and early discontinuation of ganitumab. The researchers followed this recommendation, but patients were followed for an additional 3 years.

At the 3-year mark, there were no significant differences in EFS or OS between the treatment arms. The 3-year EFS rate was 37.4% in the standard arm and 39.1% in the ganitumab arm (hazard ratio [HR], 1.00; 95% CI, 0.76 to 1.33; P =.50). The 3-year OS rate was 59.5% in the standard arm and 56.7% in the ganitumab arm (HR, 1.03; 95% CI, 0.75-1.42; P =.99).

Rates of grade 3 or higher toxicities were mostly similar between the treatment arms, the researchers reported. However, patients in the ganitumab arm had higher rates of grade 3 febrile neutropenia (48.0% vs 39.3%) and increased ALT (13.3% vs 3.4%) than patients in the standard arm. The only fatal adverse event was 1 case of pneumonitis in the ganitumab arm.

“Our results add to existing literature that demonstrate the failure of IGF-1R–directed monoclonal antibodies to improve outcomes when added to conventional chemotherapy across a range of cancers,” the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


DuBois SG, Krailo MD, Glade-Bender J, et al. 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. Published online January 20, 2023. doi:10.1200/JCO.22.01815