Ifosfamide is likely to be the go-to therapy in recurrent Ewing sarcoma

Ifosfamide was more efficacious than topotecan plus cyclophosphamide in patients with primary recurrent or refractory Ewing sarcoma, despite a higher discontinuation rate due to toxicity in the ifosfamide arm. The phase 3 rEECur trial is the first randomised study to deliver efficacy, safety, and quality-of-life data to inform physicians on chemotherapy treatment decisions for patients with recurrent Ewing sarcoma.

Dr Martin McCabe (University of Manchester, UK) noted that there is no established standard-of-care for patients with recurrent/refractory Ewing sarcoma, because there have not been any randomised trials comparing different chemotherapy regimens in this population [1]. Therefore, the phase 3 rEECur trial randomised patients with previously treated Ewing sarcoma to ifosfamide (IFOS; n=78) or topotecan and cyclophosphamide (TC; n=162). The primary outcome was event-free survival (EFS).

The median EFS was numerically higher in the IFOS arm (5.7 months) than in the TC arm (3.5 months) and trended towards significance (95% CI 0.51‒1.05). In addition, the 6-month EFS rates were 47% and 37% in the IFOS and TC 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 IFOS arm and a median OS of 10.5 months in the TC arm, with a trend towards a significant difference (95% CI 0.50‒1.08).

The rate of ≥ grade 3 adverse events (AEs) was higher in the IFOS arm (57%) than in the TC arm (44%), mainly due to a higher rate of nervous system (8% vs 3%) and renal/urinary disorders (8% vs 0%) in the IFOS arm. In the TC arm, 53% of the patients discontinued due to progression compared with 22% in the IFOS arm. However, 26% of the patients in the IFOS group discontinued due to AEs but no patients in the TC group did so. Dr McCabe commented that this was a high-dose trial and that dose reductions were not allowed in the IFOS arm. In the TC arm, dose reductions were allowed. Finally, quality of life data suggested that improvements were made in the IFOS arm but not in the TC arm.

1. 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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Posted on 9 June, 202221 June, 2022