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Emerging Novel Agents for Patients with Advanced Ewing Sarcoma: a Report from the Children's Oncology Group (COG) New Agents for Ewing Sarcoma Task Force

Abstract

Ewing sarcoma is a small round blue cell malignancy arising from bone or soft tissue and most commonly affects adolescents and young adults. Metastatic and relapsed Ewing sarcoma have poor outcomes and recurrences remain common. Owing to the poor outcomes associated with advanced disease and the need for a clear research strategy, the Children's Oncology Group Bone Tumor Committee formed the New Agents for Ewing Sarcoma Task Force to bring together experts in the field to evaluate and prioritize new agents for incorporation into clinical trials. This group's mission was to evaluate scientific and clinical challenges in moving new agents forward and to recommend agents and trial designs to the Bone Tumor Committee. The task force generated a framework for vetting prospective agents that included critical evaluation of each drug by using both clinical and non-clinical parameters. Representative appraisal of agents of highest priority, including eribulin, dinutuximab, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, anti-angiogenic tyrosine kinase inhibitors, and poly-ADP-ribose polymerase (PARP) inhibitors, is described. The task force continues to analyze new compounds by using the paradigm established.

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References
1.
Ladenstein R, Potschger U, Cecile Le Deley M, Whelan J, Paulussen M, Oberlin O . Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial. J Clin Oncol. 2010; 28(20):3284-91. DOI: 10.1200/JCO.2009.22.9864. View

2.
Okouneva T, Azarenko O, Wilson L, Littlefield B, Jordan M . Inhibition of centromere dynamics by eribulin (E7389) during mitotic metaphase. Mol Cancer Ther. 2008; 7(7):2003-11. PMC: 2562299. DOI: 10.1158/1535-7163.MCT-08-0095. View

3.
Chuk M, Widemann B, Minard C, Liu X, Kim A, Bernhardt M . A phase 1 study of cabozantinib in children and adolescents with recurrent or refractory solid tumors, including CNS tumors: Trial ADVL1211, a report from the Children's Oncology Group. Pediatr Blood Cancer. 2018; 65(8):e27077. PMC: 6082380. DOI: 10.1002/pbc.27077. View

4.
Iniguez A, Stolte B, Wang E, Conway A, Alexe G, Dharia N . EWS/FLI Confers Tumor Cell Synthetic Lethality to CDK12 Inhibition in Ewing Sarcoma. Cancer Cell. 2018; 33(2):202-216.e6. PMC: 5846483. DOI: 10.1016/j.ccell.2017.12.009. View

5.
Serrano M, Hannon G, Beach D . A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993; 366(6456):704-7. DOI: 10.1038/366704a0. View