Addition of zoledronic acid to consolidation chemotherapy in Ewing sarcoma-EURO EWING 2012 (EE2012): an international, open-label, randomised controlled phase III trial.

BACKGROUND

Pre-clinical data demonstrated anti-tumour effect in Ewing sarcoma (ES) for zoledronic acid. This provided the rationale for the second randomisation (R2) in the EURO EWING 2012 (EE2012) trial, whether the addition of zoledronic acid to consolidation chemotherapy improved clinical outcomes.

METHODS

EE2012 was a European academic, open-label, randomised controlled phase III clinical trial. Patients with ES or Ewing-like sarcomas were included (R1). Patients meeting the R2 eligibility criteria (age 5-49 years) were randomised (1:1) to receive either nine cycles of zoledronic acid or no zoledronic acid with the R1 allocated consolidation chemotherapy. Primary and secondary outcome measures were event-free and overall survival, respectively.

FINDINGS: Between 12-Aug-2014 and 20-Sep-2019, of the 640 R1 patients, 272 patients (136 in each group) were enrolled to R2. Median follow-up was 5.5 years. Three-year EFS was 59% in the zoledronic acid group and 57% in the no zoledronic acid group (adjusted hazard ratio = 0·92 (95% CI: 0·64, 1.31), p = 0.632). Three-year OS was 75% for both groups (adjusted hazard ratio = 0.84 (95% CI: 0.56, 1.25), p = 0.386).

CONCLUSION

Adding zoledronic acid did not improve clinical outcomes in ES.

TRIAL REGISTRATION: The trial was prospectively registered with EudraCT 2012-002107-17 and ISRCTN 54540667.