Management of recurrent or refractory Ewing sarcoma: A systematic review of phase II clinical trials in the last 15 years

The aim of the present study was to evaluate the antitumor activity of drugs in phase II clinical trials for recurrent or refractory EWS. A systematic review was performed using clinical trials from four data sources: i) ClinicalTrials.gov; ii) PubMed; iii) Clinicaltrialsregister.eu; and iv) American Society of Clinical Oncology. The search terms included: (Ewing sarcoma OR Ewing family of tumors) AND (phase II OR phase I/II)'. Overall, 465 trials were identified and 64 were included in the present study, of which, 37 had published results. The highest objective response rate came from irinotecan-based chemotherapy. Currently, the majority of targeted therapy has failed to demonstrate any activity except for regorafenib. Trials using anti-angiogenesis small molecular tyrosine kinase inhibitors (aaTKIs) are currently ongoing with promising early results. For immunotherapy, anti-insulin like growth factor 1 receptor antibody demonstrated disappointing activity. The best outcome came from irinotecan-based regimens. Targeted therapy with aaTKIs is worthy of further investigation, with immunotherapy is not recommended for off-label use.