A treatment intensification approach does not improve outcomes in patients with metastatic Ewing sarcoma, according to a phase 3 trial published in the Journal of Clinical Oncology.

Adding high-dose treosulfan and melphalan (TreoMel-HDT) followed by autologous stem cell reinfusion to standard chemotherapy did not improve event-free survival (EFS) or overall survival (OS) in the overall cohort. 

However, there was an EFS benefit with TreoMel-HDT in patients younger than 14 years. 

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The trial (ClinicalTrials.gov Identifier: NCT00987636) enrolled 109 patients who had disseminated Ewing sarcoma with metastases to bone and/or other sites. The patients’ median age was 15.8 years (range, 4.4-45.4 years), and half of them were male.

All patients received induction therapy with 6 cycles of vincristine, ifosfamide, doxorubicin, and etoposide. Patients were then randomly assigned to receive 8 cycles of vincristine, actinomycin D, and cyclophosphamide (VAC) alone (n=54) or VAC plus TreoMel-HDT (n=55). 

At a median follow-up of 3.3 years, no significant difference in EFS was noted between the TreoMel-HDT arm and the control arm (hazard ratio [HR], 0.72; 95% CI, 0.46 to 1.12; P =.37). The 3-year EFS rate was 20.9% in the TreoMel-HDT arm and 19.2% in the control arm.  

However, among patients 14 years or younger, there was an EFS benefit with TreoMel-HDT. The 3-year EFS rate was 39.3% in the TreoMel-HDT arm and 9% in the control arm (HR, 0.40; 95% CI, 0.19-0.87; P =.0159). 

On the other hand, there was no significant difference in OS between the arms (HR, 0.96; 95% CI, 0.58-1.58; P =.87). The 3-year OS rate was 43.4% in the TreoMel-HDT arm and 37.4% in the control arm. The 5-year OS rate was 26.8% and 33.6%, respectively. 

The most common severe toxicities in the TreoMel-HDT and control arms were hematologic toxicity (97.7% vs 82.5%), gut toxicity (47.7% vs 9.5%), general condition toxicity (25.6% vs 6.3%), and infection (38.6% vs 12.7%).  

“Treatment intensification does not improve the outcome in metastatic Ewing sarcoma,” the researchers concluded. “Further studies using novel targeted therapies and improved molecular and genomic tools need to be evaluated in future trials.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Koch R, Gelderblom H, Haveman L, et al. High-dose treosulfan and melphalan as consolidation therapy versus standard therapy for high-risk (metastatic) Ewing sarcoma. J Clin Oncol. Published online April 15, 2022. doi:10.1200/JCO.21.01942