Recurrent and Refractory Ewing Sarcoma Phase I/II Trials: Current Perspective From the Euro-Ewing Consortium
Year: 2025
Type: article
Study design: Systematic Review
Abstract: PURPOSE: Updated analysis of phase I/II trials in recurrent/refractory (R/R) Ewing sarcoma (EwS) over the past 11 years. METHODS: A systematic review was performed to identify phase I/II trials for R/R EwS in three databases (WHO, US National Library of Medicine, and European Clinical Trials Database) and/or published in PubMed/ASCO/European Society for Medical Oncology websites from 2014 to 2024. The search criteria included EwS OR bone sarcoma OR sarcoma AND Phase-I OR Phase-II. Eligibility and data extraction were performed independently by three reviewers, with priority given to trials with EwS specified data. Trials were categorized by therapeutic intervention, including targeted therapies, immunotherapy, chemotherapy, and combined therapies. RESULTS: One hundred eight trials met inclusion criteria, predominantly academic (70%) and multicenter (81.5%), with significant US and European collaboration. Trial designs were mainly single-arm, with an increase in multiarm trials in the recent years and increased focus on the pediatric population. Trial modalities emphasized targeted therapies with tyrosine kinase, poly-ADP ribose polymerase, EWSR1::FLI1, and cell cycle inhibitors. Immunotherapy with monoclonal antibodies and CAR-T cells as primary agents is also under investigation. The COVID-19 pandemic coincided with a marked reduction in trial initiation in 2020. Among evaluable data, disease control rates averaged 44% and response rates 8%. CONCLUSION: This review highlights evolving therapeutic directions in R/R EwS, with increased emphasis on targeted therapies and immunotherapies. Despite pandemic-related delays, trials have progressed in exploring novel targets, including EWSR1::FLI1 oncogenic fusion and DNA repair pathways. These findings underscore ongoing global efforts to address critical unmet needs in EwS treatment, offering a foundation for future trial designs, especially international, randomized phase-II trials across all age ranges.
Source: JCO Precision Oncology
DOI: 10.1200/po-25-00377
Institutions: Hospital Universitari i Politècnic La Fe, Centre Hospitalier Universitaire de Martinique, Epidémiologie clinique et vieillissement, Instituto de Investigación Sanitaria La Fe, Centre Léon Bérard, Université Paris-Saclay, Institut Gustave Roussy, Birmingham Women’s and Children’s NHS Foundation Trust, University of Birmingham, German Cancer Research Center, Heidelberg University, University Hospital Heidelberg, National Center for Tumor Diseases, Hopp Children's Cancer Center Heidelberg, Deutsches Konsortium für Translationale Krebsforschung, Karolinska Institutet, University of Miami, Istituto Ortopedico Rizzoli, Sylvester Comprehensive Cancer Center, Anticancer Fund, University College London, University of Zurich, University of Manchester, The Christie NHS Foundation Trust
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4414346950