Metastatic Ewing Sarcoma, Patterns of Care and Outcomes of Patients in a Real-Life National Setting Over a Decade

Metastatic Ewing sarcoma (MES) has a poor prognosis. This multicenter observational study provides real-world data on treatment patterns of patients with MES in France. Treatment characteristics, outcomes such as time to next treatment (TTNT) and overall survival (OS), and prognostic factors of patients aged ≥ 12 years treated for a MES in 11 French reference network centers were retrieved from our national database. From 2008 to 2018, 156 patients with MES were included: 82 were metastatic at diagnosis (upfront metastatic cohort), 74 had developed secondary metastases after treatment of a localized disease (metastatic relapse cohort). 94% of patients received systemic treatment, with a median of three lines (1-11), 61% had at least one loco-regional procedure and 42% of patients participated in a clinical trial in the metastatic setting. Median OS from metastatic diagnosis was 20.3 months [95% CI 14.0; 27.7] in the metastatic relapse cohort and 31.4 months [95% CI 26.5; 42.5] in the upfront metastatic cohort (p = 0.02). Median TTNT in first metastatic line was 16.8 months [95% CI 12.9; 21.3] in the upfront metastatic cohort and 7.4 months [95% CI 5.0; 11.1] in the metastatic relapse cohort, 5.8 months [95% CI 3.6; 7.3] in 2nd line and 3.8 months [95% CI 2.8; 5.7] in 3rd line, without significant difference between cohorts and treatment regimens. Patients with upfront MES have a longer OS than patients with relapsing disease, mainly due to first metastatic line dose-dense polychemotherapy and loco-regional procedures in selected patients. Main regimens used at relapse are associated with the same range of benefit and survival, while TKIs such as regorafenib or cabozantinib have modest activity. Inclusion in clinical trials should be prioritized.