Chemotherapy

In the Intergroup Ewing Sarcoma Study, patients with metastatic disease showed no benefit from the addition of ifosfamide and etoposide to a standard regimen of vincristine, doxorubicin, cyclophosphamide, and dactinomycin.[8]

In another Intergroup study, increasing dose intensity of cyclophosphamide, ifosfamide, and doxorubicin did not improve outcome compared with regimens using standard-dose intensity. This regimen increased toxicity and risk of second malignancy without improving EFS or OS.[2]

Intensification of ifosfamide to 2.8 g/m2 per day for 5 days did not improve outcome when administered with standard chemotherapy in patients with newly diagnosed metastatic Ewing sarcoma.[9][Level of evidence C2]

A pilot study of low-dose anti-angiogenic therapy with vinblastine and celecoxib added to every-3-week therapy with VDC/IE did not improve outcomes for patients presenting with metastases.[10]

The Children's Oncology Group performed a prospective randomized trial (AEWS1221 [NCT02306161]) that tested the addition of ganitumab to multiagent chemotherapy. Patients were randomly assigned (1:1) at enrollment to either the standard arm (interval-compressed VDC/IE) or the experimental arm (ganitumab is given with VDC/IE when the cycle starts and as monotherapy once every 3 weeks for 6 months after conventional therapy). The study enrolled 298 eligible patients (148 in standard arm; 150 in experimental arm).[11][Level of evidence B1]

The Children's Oncology Group performed a prospective randomized trial (AEWS1221 [NCT02306161]) that tested the addition of ganitumab to multiagent chemotherapy. Patients were randomly assigned (1:1) at enrollment to either the standard arm (interval-compressed VDC/IE) or the experimental arm (ganitumab is given with VDC/IE when the cycle starts and as monotherapy once every 3 weeks for 6 months after conventional therapy). The study enrolled 298 eligible patients (148 in standard arm; 150 in experimental arm).[11][Level of evidence B1]

The 3-year EFS rate estimates were 37.4% (95% confidence interval [CI], 29.3%–45.5%) for patients in the standard arm and 39.1% (95% CI, 31.3%–46.7%) for patients in the experimental arm (stratified EFS-event hazard ratio [HR] for experimental arm, 1.00; 95% CI, 0.76–1.33; 1-sided, P = .50).

The Children's Oncology Group performed a prospective randomized trial (AEWS1221 [NCT02306161]) that tested the addition of ganitumab to multiagent chemotherapy. Patients were randomly assigned (1:1) at enrollment to either the standard arm (interval-compressed VDC/IE) or the experimental arm (ganitumab is given with VDC/IE when the cycle starts and as monotherapy once every 3 weeks for 6 months after conventional therapy). The study enrolled 298 eligible patients (148 in standard arm; 150 in experimental arm).[11][Level of evidence B1]

Patients in the experimental arm reported more cases of pneumonitis after radiation therapy involving thoracic fields and nominally higher rates of febrile neutropenia and alanine transaminase elevation.

The Children's Oncology Group performed a prospective randomized trial (AEWS1221 [NCT02306161]) that tested the addition of ganitumab to multiagent chemotherapy. Patients were randomly assigned (1:1) at enrollment to either the standard arm (interval-compressed VDC/IE) or the experimental arm (ganitumab is given with VDC/IE when the cycle starts and as monotherapy once every 3 weeks for 6 months after conventional therapy). The study enrolled 298 eligible patients (148 in standard arm; 150 in experimental arm).[11][Level of evidence B1]

Ganitumab added to interval-compressed chemotherapy did not significantly reduce the risk of an EFS event in patients with newly diagnosed metastatic Ewing sarcoma. The outcomes of these patients were similar to those in previous trials who did not receive IGF-1R inhibition or interval compression.

The Children's Oncology Group performed a prospective randomized trial (AEWS1221 [NCT02306161]) that tested the addition of ganitumab to multiagent chemotherapy. Patients were randomly assigned (1:1) at enrollment to either the standard arm (interval-compressed VDC/IE) or the experimental arm (ganitumab is given with VDC/IE when the cycle starts and as monotherapy once every 3 weeks for 6 months after conventional therapy). The study enrolled 298 eligible patients (148 in standard arm; 150 in experimental arm).[11][Level of evidence B1]

The addition of ganitumab may be associated with increased toxicity.