Phase 3 randomized trial of postirradiation chemotherapy in patients with newly diagnosed ependymoma: A report from the Children’s Oncology Group

BACKGROUND: The utility of chemotherapy for childhood ependymoma is uncertain without a prior randomized trial. METHODS: ACNS0831, a multi-center phase 3 randomized study conducted through the Children's Oncology Group (COG), included patients 1-21 years with newly diagnosed intracranial ependymoma. Patients with complete/near total resections (GTR/NTR) or complete response (CR) to induction therapy were randomized to radiation (RT) alone or RT followed by chemotherapy (RT-CHEMO). Primary outcomes were event free survival (EFS) and overall survival (OS). Due to anticipated non-compliance with chemotherapy, an 'as treated' analysis was planned. Patients with sub-total resection (STR) were non-randomly assigned to RT-CHEMO. Grade 2 supratentorial tumors, GTR or CR to induction therapy were observed. RESULTS: Of 449 eligible patients, 325 with GTR/NTR or CR were randomized. Five-year EFS was 63.7% (95% CI 55.1-71.1%) for RT only (n = 161) versus 69.2% (60.8-76.3%) for RT-CHEMO (n = 164) (one-sided log-rank p = 0.299, HR = 0.866). Five-year OS was 86.9% (79.8-91.6%) for RT only versus 88.3% (81.8-92.6%) for RT-CHEMO (one-sided log-rank p-value = 0.172, HR = 0.757). The 'as treated' and 'as randomized' analysis results were similar. Sixty-three subjects with STR were assigned to RT-CHEMO; 5-year EFS was 33.6% (22·1-45·5%) and OS 74.0% (60.5-83.5%). Supratentorial grade 2 tumors with GTR or CR were observed with a 5-year EFS of 66.9% (49.0-79.7%) and OS of 100%. Molecular classification was provided for 94% (n = 422) of all subjects. CONCLUSIONS: Primary analysis showed no benefit for maintenance chemotherapy. Further follow-up is important to assess its effect on late relapses. This is the largest cohort of molecularly classified ependymomas treated on a Phase 3 randomized trial.