Journal Article Ahead of print
PubMed: 41249450 DOI: 10.1038/s41416-025-03263-3
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.
Br J Cancer
Authors: Valérie Laurence, Nina Jehanno, Sylvain Dureau, Lieke Mous, Line Claude, Stelly Ballet, Gaëlle Pierron, Nathalie Gaspar, Mehdi Brahmi, Thibaud Valentin, Gabriel Revon-Rivière, Cyril Lervat, Jamie Probert, Natacha Entz-Werle, Ludovic Mansuy, Dominique Plantaz, Maria Rios, Laure Saumet, Cécile Vérité, Marie-Pierre Castex, Estelle Thebaud, Thibaut Cassou-Mounat, Anne-Sophie Plissonnier, Jennifer Dieppedale, Olivier Delattre, Marie-Emmanuelle Legrier, Perrine Marec-Bérard, François Gouin, Pablo Berlanga, Camille Cordero, Didier Surdez, Nadège Corradini
Affiliations
- Adolescents and Young Adults Unit, Medical Oncology and SIREDO (Care, Innovation and Research for Children, Adolescents, and Young Adults with Cancer) Departments, Curie Institute, Paris, France.
- Department of Nuclear Medicine, Curie Institute, Paris, France.
- Department of Biometry, Curie Institute, Saint Cloud, France.
- Balgrist University Hospital, Faculty of Medicine, University of Zurich (UZH), Zurich, Switzerland.
- Department of Radiation Oncology, Centre Léon Bérard, Lyon, France.
- Genetics Department Curie Institute & PSL Research University, Paris, France.
- Department of Oncology for Children and Adolescents, Gustave Roussy Institute, Villejuif, France.
- Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
- Department of Medical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France.
- Department of Pediatric Hematology, Immunology and Oncology, APHM - La Timone Children's Hospital, Marseille, France.
- Department of Pediatric and AYA Oncology, Centre Oscar Lambret, Lille, France.
- Department of Pediatric Onco-hematology, University Hospital of Rennes, Rennes, France.
- Department of Pediatric Onco-hematology, University Hospitals of Strasbourg, Strasbourg, France.
- Department of Pediatric Hematology and Oncology, Children's University Hospital, Nancy, France.
- Department of Pediatric Hematology and Oncology, University Hospital of Grenoble, Grenoble, France.
- Department of Medical Oncology, Institut de Cancérologie de Lorraine-Alexis Vautrin, Vandoeuvre-lès-Nancy, France.
- Department of Pediatric Onco-Hematology, University Hospital of Montpellier, Montpellier, Languedoc-Roussillon, France.
- Department of Pediatric and Adolescent Hematology and Oncology, Pellegrin Hospital, Bordeaux, France.
- Pediatric Oncology Immunology Hematology Unit, Children's University Hospital - Toulouse University Hospital, Toulouse, France.
- Department of Pediatric Oncology, Hôpital Mère-Enfant, Nantes, France.
- Nuclear Medicine Department, Institut Claudius Regaud, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France.
- DREH Pôle Promotion, Institut Curie, Saint-Cloud, France.
- INSERM U830, Diversity and Plasticity of Childhood Tumors Lab, SIREDO Oncology Center, Curie Institute Research Center, PSL Research University, Paris, France.
- Department of Pediatric Oncology, Institute for Paediatric Haematology and Oncology, Centre Léon Bérard, Lyon, France.
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France.
- Department of Pediatric Oncology, Institute for Paediatric Haematology and Oncology, Centre Léon Bérard, Lyon, France.
Abstract
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.
MeSH
Sarcoma, Ewing, Tomography, Neoplasms, Positron Emission Tomography Computed Tomography, Maintenance, Sarcoma, Diagnosis, Therapeutics, Wounds And Injuries