Whelan J, et al. - In this randomized study, researchers investigated if consolidation high-dose chemotherapy could improve survival in patients with localized Ewing sarcoma (ES) at high risk for relapse. Findings revealed that, administration of busulfan and melphalan (BuMel) after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors resulted in improved event-free survival (EFS) and overall survival (OS). BuMel could be an important addition to the standard of care in this group of patients.

Methods

• Patients younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or having a tumor volume at diagnosis ≥ 200 mL if unresected, or initially resected, or resected after radiotherapy, were randomized to busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses).
• The outcome of interest was a 15% improvement in 3-year event-free survival (EFS) (hazard ratio [HR], 0.60).

Results

• Randomization of 240 patients classified as high risk (median age, 17.1 years) to VAI (n=118) or BuMel (n=122) was carried out between 2000 and 2015.
• Poor histologic response after chemotherapy alone was noted in 78% who entered the trial.
• A median follow-up of 7.8 years was carried out.
• Findings in an intent-to-treat analysis revealed that BuMel vs VAI resulted in a significant decrease in the risk of event: HR, 0.64 (95% CI, 0.43 to 0.95; P=.026); 3- and 8-year EFS were, respectively, 69.0% (95% CI, 60.2% to 76.6%) vs 56.7% (95% CI, 47.6% to 65.4%) and 60.7% (95% CI, 51.1% to 69.6%) vs 47.1% (95% CI, 37.7% to 56.8%).
• Researchers found that, BuMel also improved overall survival (OS): HR, 0.63 (95% CI, 0.41 to 0.95; P=.028); 3- and 8-year OS were, respectively, 78.0% (95% CI, 69.6% to 84.5%) vs 72.2% (95% CI, 63.3% to 79.6%) and 64.5% (95% CI, 54.4% to 73.5%) vs 55.6% (95% CI, 45.8% to 65.1%).
• In the sensitivity analysis, the findings were consistent.
• BuMel-related toxicity led to death of two patients; one died after standard chemotherapy.
• Severe acute toxicities were seen significantly more by patients on BuMel vs multiple VAI courses.