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Ewing Sarcoma Drug Therapy: Current Standard of Care and Emerging Agents

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Abstract

Ewing sarcoma is a translocation-associated sarcoma mainly impacting adolescents and young adults. The classic translocation (EWSR1::FLI1) leads to a fusion oncoprotein that functions as an aberrant transcription factor. As such, the oncogenic driver of this disease has been difficult to target pharmacologically and, therefore, the systemic therapies used to treat patients with Ewing sarcoma have typically been non-selective cytotoxic chemotherapy agents. The current review highlights recent clinical trials from the last decade that provide the evidence base for contemporary drug therapy for patients with Ewing sarcoma, while also highlighting novel therapies under active clinical investigation in this disease. We review recent trials that have led to the establishment of interval-compressed chemotherapy as an international standard for patients with newly diagnosed localized disease. We further highlight recent trials that have shown a lack of demonstrable benefit from high-dose chemotherapy or IGF-1R inhibition for patients with newly diagnosed metastatic disease. Finally, we provide an overview of chemotherapy regimens and targeted therapies used in the management of patients with recurrent Ewing sarcoma.

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Author notes

  1. Bhuvana Setty and Ajami Gikandi contributed equally.

Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology/BMT, Nationwide Children′s Hospital, The Ohio State University, Columbus, OH, USA

    Bhuvana A. Setty

  2. Harvard Medical School, Boston, MA, USA

    Ajami Gikandi

  3. Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA

    Steven G. DuBois

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BAS and AG declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. SGD reports consulting fees for advisory board participation from Amgen, Bayer and Jazz and travel expenses from Loxo Oncology, Roche and Salarius.

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Supported by Alex’s Lemonade Stand Foundation (SGD).

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Setty, B.A., Gikandi, A. & DuBois, S.G. Ewing Sarcoma Drug Therapy: Current Standard of Care and Emerging Agents. Pediatr Drugs 25, 389–397 (2023). https://doi.org/10.1007/s40272-023-00568-9

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