No established standard-of-care exists for patients with recurrent/refractory Ewing sarcoma, because there have not been any randomised trials comparing different chemotherapy regimens in this population. Therefore, the phase 3 rEECur trial, presented by Dr Martin McCabe (University of Manchester, UK), randomised patients with previously treated Ewing sarcoma to ifosfamide (n=78) or topotecan plus cyclophosphamide (n=162). The primary outcome was event-free survival (EFS) [1].
The median EFS was numerically higher in the ifosfamide arm (5.7 months) than in the topotecan plus cyclophosphamide arm (3.5 months) and trended towards significance (HR 0.73; 95% CI 0.51‒1.05). In addition, the 6-month EFS rates were 47% and 37% in the ifosfamide and topotecan plus cyclophosphamide arm, respectively. Interestingly, exploratory subgroup analysis revealed that the effect appeared to be more pronounced in younger patients (<14 years; HR 0.37) than in older patients (HR 0.93). The overall survival (OS) analysis displayed similar results, with a median OS of 15.4 months in the ifosfamide arm and a median OS of 10.5 months in the topotecan plus cyclophosphamide arm, with a trend towards a significant difference (HR 0.73; 95% CI 0.50‒1.08).
The rate of grade ≥3 adverse events (AEs) was higher in the ifosfamide arm (57%) than in the topotecan plus cyclophosphamide arm (44%), mainly due to a higher rate of nervous system (8% vs 3%) and renal/urinary disorders (8% vs 0%) in the ifosfamide arm. In the topotecan plus cyclophosphamide arm, 53% of the patients discontinued due to progression compared with 22% in the ifosfamide arm. However, 26% of the patients in the ifosfamide group discontinued due to AEs but no patients in the topotecan plus cyclophosphamide group did so. Dr McCabe commented that this was a high-dose trial and that dose reductions were not allowed in the ifosfamide arm. In the topotecan plus cyclophosphamide arm, dose reductions were allowed. Finally, quality-of-life data suggested that improvements were made in the ifosfamide arm but not in the topotecan plus cyclophosphamide arm.
- McCabe MG, 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). LBA2, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.
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