Background: Ewing sarcoma (ES) is a rare tumour in which approximately 25% of patients present with metastatic disease at diagnosis. Extrapulmonary disseminated disease defines very high-risk (VHR) patients, who experience frequent relapse and have poor overall survival (OS, ~30%).
Methods: The phase II CombinaiR3 trial (NCT03011528) enrolled 45 VHR ES patients across 15 French centres (2017–2021) to assess a treatment strategy combining dose-dense induction chemotherapy, high-dose consolidation, and extended maintenance therapy. The primary endpoint was median event-free survival (EFS). Exploratory endpoints included full-body fluorine-18–fluorodeoxyglucose PET/CT scans and circulating tumour DNA (ctDNA) detection throughout treatment.
Results: Among the 42 evaluated patients (median age 14 years; range 6–47), 29 had a primary tumour volume ≥200 ml, and 35 presented with bone ± bone marrow metastatic involvement, with 18 having more than five bone lesions. At the 48-month follow-up, EFS rates at 18 and 36 months were 63.4% and 53.7%, respectively, and the 3-year OS was 65.5%. Toxicities were consistent with expectations, with no treatment-related deaths and no discontinuation of maintenance therapy due to toxicity. PET/CT and ctDNA monitoring showed a strong correlation at diagnosis and relapse.
Discussion: These findings support the proposed experimental strategy as a viable first-line approach for selected VHR ES patients and justify its inclusion in international therapeutic decision-making.
Read the original material: Interest of a sequential multimodal approach for the treatment of newly diagnosed patients with multimetastatic Ewing sarcoma: results of the French prospective CombinaiR3 phase II trial
