PHASE 2 TRIAL OF CARBOPLATIN AND BEVACIZUMAB FOR RECURRENT ADULT EPENDYMOMA. A CERN STUDY
Recommended Citation
Gilbert MR, Omuro A, Yuan Y, Mendoza T, Wall K, Grajkowska E, Vera E, Reyes J, Aldape K, Penas-Prado M, Walbert T, Mikkelsen T, Weathers S, O'Brien B, DeGroot J, Puduvalli V, Pentsova E, DeAngelis L, DeAngelis L, Kaley T, Gavrilovic I, Batchelor T, Armstrong TS. PHASE 2 TRIAL OF CARBOPLATIN AND BEVACIZUMAB FOR RECURRENT ADULT EPENDYMOMA. A CERN STUDY. Neuro-Oncology 2023; 25:ii7.
Document Type
Conference Proceeding
Publication Date
9-8-2023
Publication Title
Neuro-Oncology
Abstract
BACKGROUND: Most adults with ependymoma undergo tumor resection at the time of diagnosis, which may be followed by radiation. At recurrence, re-resection and/or (re)-irradiation may be given, however, there are few established chemotherapy treatments. A previous retrospective report of 8 patients treated with carboplatin and bevacizumab showed a high response rate with 6 patients demonstrating an imaging response (Green, Neurology 2009). We sought to further investigate this regimen with a prospective trial. MATERIAL AND METHODS: We performed a prospective phase 2 study in the CERN Adult Clinical Trials Network. Adult patients with recurrent or progressive ependymoma were enrolled to receive carboplatin (AUC =4-5) every 4 weeks for up to 6 cycles and bevacizumab at 10mg/kg every 2 weeks for one year, with the option to continue until progression or toxicity. The primary endpoint was 12-month PFS rate and >50% defined efficacy. Serial symptom burden measurement at baseline and at the time of disease evaluation using MD Anderson Symptom Inventory-brain tumor (MDASI-BT) or MDASI-Spine patient-reported outcomes (PROs) were used to evaluate the clinical impact of PFS. RESULTS: A total of 22 patients with median age of 45 years were accrued and treated; 11 were women. WHO grade was 3 in 13 patients and grade 2 in 9 patients (3 with myxopapillary ependymoma) Ten patients had only spinal cord disease, 3 had both spinal cord and brain involvement and 9 patients had brain involvement alone (6 supratentorial, 3 infratentorial). Previous treatments included radiotherapy in all 22 patients and alkylating chemotherapy in 9 patients. Treatment was well tolerated with expected myelotoxicities and hypertension. The Kaplan-Meier calculated 12-Month PFS rate was 76.4% (95%CI 52.2%, 89.4%), median PFS = 18 months (95%CI 12.2, +∞). There were 2 partial responses (9.1%). Brain tumor responders (objective response or stable disease) showed reduction while non-responders had an increase in both neurologic and cognitive symptoms but similar report of other symptoms. Spine tumor responders and non-responders both showed worsening disease-related symptoms; autonomic symptoms worsened in responders. Activity related interference worsened for all patients. CONCLUSION: This treatment regimen was safe and met the primary efficacy endpoint of 12-month PFS rate. The improvement in disease-related symptoms in brain tumor patients supports that the achieved disease stability was clinically meaningful, but the increased activity-related interference suggests that treatment-associated symptoms may impact work, general activity, and walking ability during treatment. Improvements in spine tumor disease-associated symptoms were not seen. A confirmatory trial is warranted to further investigate the findings and to determine if there are differences in response amongst ependymoma subtypes and tumor location.
PubMed ID
Not assigned.
Volume
25
First Page
ii7
