High-dose ifosfamide is more effective than topotecan plus cyclophosphamide for patients with relapsed or refractory Ewing sarcoma, according to a study presented at the 2022 ASCO Annual Meeting. 

The study was the first trial of its kind in this setting, according to study author Martin McCabe, MB BChir, PhD, of the University of Manchester in the United Kingdom.

The phase 2/3 rEECur trial enrolled children and adults (ages 2-50 years) with relapsed/refractory Ewing sarcoma. The patients were initially randomized into 4 treatment arms — high-dose ifosfamide, topotecan plus cyclophosphamide, irinotecan plus temozolomide, or gemcitabine plus docetaxel. 

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Based on early efficacy data, recruitment was stopped for the gemcitabine-docetaxel and irinotecan-temozolomide arms. 

The phase 3 portion of the study included only 73 patients from the ifosfamide arm and 73 from the topotecan-cyclophosphamide arm. Topotecan was given at 0.75 mg/m2, cyclophosphamide at 250 mg/m2, and ifosfamide at 3000 mg/m2, all on days 1 to 5 of each cycle.

The median follow-up was 47 months. The median event-free survival (EFS) was 5.7 months with ifosfamide and 3.5 months with topotecan-cyclophosphamide (hazard ratio [HR], 0.73; 95% CI, 0.51-1.05). The 6-month EFS rate was 47% and 37%, respectively.

The median overall survival (OS) was 15.4 months with ifosfamide and 10.5 months with topotecan-cyclophosphamide (HR, 0.73; 95% CI, 0.50-1.08). The 1-year OS rate was 55% and 45%, respectively.

Dr McCabe noted that the OS benefit with ifosfamide appeared to be more pronounced in patients 14 years of age or younger.

The rate of grade 3 or higher adverse events was higher in the ifosfamide arm than in the topotecan-cyclophosphamide arm — 57% and 44%, respectively. Discontinuation due to toxicity occurred in 26% of patients in the ifosfamide arm and 0% in the topotecan-cyclophosphamide arm. 

Dr McCabe noted that some questions remain regarding the 2 treatment arms that were dropped early on. However, data from this trial can help with patient management and the design of future trials. 

The rEECur trial is currently recruiting patients to the ifosfamide arm and to an arm consisting of carboplatin plus etoposide. The researchers plan to introduce an arm for ifosfamide plus lenvatinib later this year. 

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


McCabe M, Kirton L, Khan M, et al. Phase III assessment of topotecan and cyclophosphamide and high-dose ifosfamide in rEECur: An international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES). Presented at ASCO 2022; June 3-7, 2022. Abstract LBA2.