CERN 09-02: A phase 2 trial of carboplatin and bevacizumab for recurrent adult ependymomas.

Background: Salvage therapies for adults with recurrent ependymoma are limited. A prior retrospective review of patients with recurrent ependymomas treated with bevacizumab and carboplatin reported a 75% radiographic response rate. This prospective single-arm, open-label Phase 2 study was designed to assess clinical efficacy of this regimen. Methods: Twenty-two patients were evaluated in this CERN Adult Clinical Trials network study. Adult patients (age ≥18) with recurrent ependymomas received carboplatin (AUC = 5-6) every 4 weeks and bevacizumab 10mg/kg every 2 weeks for 6 cycles, after which carboplatin was discontinued, while bevacizumab could be continued at physician's discretion. Imaging of areas involved and patient-reported outcomes (PRO) with the MD Anderson Symptom Inventory (brain and/or spine modules) were assessed at baseline and every 2 cycles. Results: With a median follow-up time of 25.9 months (mo), the primary endpoint of 12-mo progression-free survival rate (PFS-12) greater than 50% was reached, with a rate of 76.4% (95% CI, 52.2, 89.4). The median PFS of this cohort was 18.0 mo. Two patients achieved objective partial responses (9.1%). There were no treatment-related grade ≥4 toxicities. Brain tumor responders (radiographic objective response or stable disease) experienced improved cognitive and neurological symptoms, while spine tumor patients reported worsening symptom outcomes regardless of response. Conclusions: Treatment with carboplatin and bevacizumab in adult recurrent ependymomas met the PFS-12 clinical efficacy endpoint. However, symptomatic worsening in spinal tumors suggests imaging stability and symptom improvement in brain disease may be related to bevacizumab pseudo-response.