CTNI-66. CERN 09-02: A PHASE 2 TRIAL OF CARBOPLATIN AND BEVACIZUMAB FOR RECURRENT ADULT EPENDYMOMA

Abstract BACKGROUND Salvage therapies for adults with recurrent ependymoma are limited. A prior retrospective review of patients with recurrent ependymoma treated with bevacizumab and carboplatin reported a 75% radiographic response rate. This prospective single arm, open label Phase 2 study was designed to confirm these results. METHODS 22 patients were evaluated in this CERN Adult Clinical Trials network study. Adult patients (age≥18) with recurrent ependymoma were treated with both carboplatin (AUC = 5 -6) every 4 weeks and bevacizumab 10mg/kg every 2 weeks for 6 cycles, after which carboplatin was discontinued, and bevacizumab could be continued at physician’s discretion. Imaging of areas involved by tumor, and patient reported outcomes with the MD Anderson Symptom Inventory questionnaires (brain and/or spine modules) were assessed at baseline and every 2 cycles to evaluate response and symptom burden, respectively. RESULTS With a median follow-up time of 25.9 months, the primary end point of 12-month 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 months. Two patients achieved a partial response (9.1%). There were no treatment-related grade 4 toxicities. Improved cognitive and neurological symptoms were observed in brain tumor responders, while spine tumor patients had worsening symptom outcomes regardless of response. CONCLUSIONS Treatment with carboplatin and bevacizumab in adult recurrent ependymoma reached the PFS-12 clinical efficacy threshold, suggesting that this treatment has efficacy in this patient population. However, symptomatic worsening in patients with spinal cord disease does raise concerns that bevacizumab pseudoresponse may account for some imaging stability and symptom improvement with brain disease.