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
Mené en France sur 42 patients atteints d'un sarcome d'Ewing multimétastatique récemment diagnostiqué (âge médian : 14 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans événement, et la toxicité d'un traitement multimodal séquentiel (chimiothérapie d'induction à doses intensifiées, chimiothérapie de consolidation à forte dose, traitement d'entretien prolongé)
Background: Ewing sarcoma (ES) is a rare tumour with metastatic spread in ~25% of cases at diagnosis. Extrapulmonary disseminated disease defines very high-risk (VHR) patients, with frequent relapse and poor overall survival (OS, ~30%).
Methods: The phase II CombinaiR3 trial (NCT03011528) enroled 45 VHR ES patients across 15 French centres (2017–2021) to evaluate a strategy combining dose-dense induction chemotherapy, high-dose consolidation, and prolonged maintenance therapy. The primary endpoint was median event-free survival (EFS). Exploratory endpoints included full-body-fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) and circulating tumour DNA (ctDNA) detection during treatment.
Results: Among 42 analysed patients (median age 14 years, range 6–47), 29 had a primary tumour volume ≥200 ml, and 35 presented with bone ± bone marrow metastatic lesions, 18 exhibiting more than 5 bone lesions. At 48-month follow-up, 18- and 36-month EFS rates were 63.4% and 53.7%, respectively, with 3-year OS at 65.5%. Toxicity was as expected, with no treatment-related deaths or maintenance therapy discontinuations due to toxicity. PET/CT and ctDNA monitoring showed strong correlation at diagnosis and relapse.
Discussion: This study supports the proposed experimental strategy as a first-line option for selected VHR ES patients, warranting integration into international therapeutic discussions.
British Journal of Cancer , résumé, 2025