Ewing sarcoma: investigational mono- and combination therapies in clinical trials

Introduction Over the last decades, multi-institutional clinical trials have resulted in significant improvements in the outcomes of patients with localized Ewing sarcoma; however, those with metastatic and recurrent diseases continue to fare poorly. More recently, advancements made in understanding the biology of the disease and mechanisms of response to therapy have opened the door for the incorporation of targeted therapies. Here we review the current state of treatment for Ewing sarcoma and the most recent preclinical advancements that have the potential to translate to improved care. Areas Covered This review provides a general overview of the most recent clinical trials completed in Ewing sarcoma, as well as the preclinical and translational data that has the potential to be incorporated into clinical trials. A PubMed review as well as a review of published meeting abstracts was used to compose this review. Expert Opinion While dose-intenstifying strategies have failed to lead to improvements in outcomes for patients with the highest-risk disease, recent preclinical advancements have shed light on potential new targeted strategies. The lack of early-phase clinical trial responses should not deter us from further developing these agents, but instead should guide us in designing novel combination strategies.