Adding vincristine, topotecan, and cyclophosphamide (VTC) to 5-drug interval compressed chemotherapy did not significantly improve survival for patients with previously untreated Ewing sarcoma (EWS) in a phase 3 trial.
However, patients in this trial have “the best survival estimates to date,” according to researchers. They reported these results in the Journal of Clinical Oncology.
The phase 3 trial (ClinicalTrials.gov Identifier: NCT01231906) enrolled 629 eligible patients with extracranial nonmetastatic EWS or primitive neuroectodermal tumor of bone or soft tissue. At baseline, the patients’ median age was 13 years (range, 0-34 years), 57% were male, and 86% were White.
Of the eligible patients, 309 were randomly assigned to regimen A, which was standard 5-drug interval compressed chemotherapy. The regimen consisted of 5 cycles of vincristine, doxorubicin, and cyclophosphamide; 4 cycles of vincristine and cyclophosphamide; and 8 cycles of ifosfamide and etoposide.
The other 320 patients were randomly assigned to regimen B. These patients received 5 cycles of VTC; 5 cycles of vincristine, doxorubicin, and cyclophosphamide; and 7 cycles of ifosfamide and etoposide.
All patients received 6 cycles of induction (12 weeks) and 11 cycles of consolidation (22 weeks). Randomization was stratified according to age at enrollment (<18 years vs ≥18 years) and tumor site (pelvic bone, nonpelvic bone, or extraosseous).
Results: Survival and Safety
For the entire cohort, the estimated 5-year event-free survival (EFS) rate was 78%, and the 5-year overall survival (OS) rate was 87%.
The 5-year EFS was 78% with regimen A and 79% with regimen B (relative hazard rate [RHR] 0.86; 95% CI, 0.62-1.2; P =.192). The 5-year OS was 86% with regimen A and 88% with regimen B (RHR, 0.81; 95% CI, 0.54-1.2; P =.159).
The researchers reported no differences in toxicity between the treatment arms. In each arm, 2 patients experienced death as a first event. Second malignant neoplasms occurred in 14 patients on regimen A and 13 on regimen B.
For both treatment arms together, the 5-year EFS rate was 79% for patients younger than 18 years and 75% for patients age 18 or older (RHR, 1.25; 95% CI, 0.82-1.9; P =.294). The 5-year OS rates were 89% and 78%, respectively (RHR, 1.84; 95% CI, 1.15-2.96; P =.00993).
The 5-year EFS rate was 75% for patients with pelvic bone primary tumors, 78% for those with nonpelvic bone primary tumors, and 85% for patients with extraosseous primary tumors. Relative to pelvic bone primary tumors, the RHR was 0.84 (95% CI, 0.56-1.26) for bone nonpelvic tumors and 0.58 (95% CI, 0.33-1.03) for extraosseous tumors (global P =.124).
The 5-year OS rate was 87% for patients with pelvic bone primary tumors, 85% for those with nonpelvic bone primary tumors, and 92% for patients with extraosseous primary tumors. Relative to pelvic bone primary tumors, the RHR was 1.03 (95% CI, 0.61-1.73) for bone nonpelvic tumors and 0.61 (95% CI, 0.29-1.29) for extraosseous tumors (global P =.205).
“The addition of VTC to 5-drug interval compressed chemotherapy did not improve EFS or OS for the study population,” the researchers wrote. “However, the 5-year EFS and OS in this trial represent the best reported outcomes for patients with previously untreated nonmetastatic EWS to date.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Leavey PJ, Laack NN, Krailo MD, et al. Phase III trial adding vincristine-topotecan-cyclophosphamide to the initial treatment of patients with nonmetastatic Ewing sarcoma: A Children’s Oncology Group report. J Clin Oncol. Published online October 15, 2021. doi:10.1200/JCO.21.00358