Dataset Information
A Bayesian adaptive randomized phase II multicenter trial of bevacizumab with or without vorinostat in adults with recurrent glioblastoma.
Ontology highlight
ABSTRACT: Background
Bevacizumab has promising activity against recurrent glioblastoma (GBM). However, acquired resistance to this agent results in tumor recurrence. We hypothesized that vorinostat, a histone deacetylase (HDAC) inhibitor with anti-angiogenic effects, would prevent acquired resistance to bevacizumab.Methods
This multicenter phase II trial used a Bayesian adaptive design to randomize patients with recurrent GBM to bevacizumab alone or bevacizumab plus vorinostat with the primary endpoint of progression-free survival (PFS) and secondary endpoints of overall survival (OS) and clinical outcomes assessment (MD Anderson Symptom Inventory Brain Tumor module [MDASI-BT]). Eligible patients were adults (?18 y) with histologically confirmed GBM recurrent after prior radiation therapy, with adequate organ function, KPS??60, and no prior bevacizumab or HDAC inhibitors.Results
Ninety patients (bevacizumab?+?vorinostat: 49, bevacizumab: 41) were enrolled, of whom 74 were evaluable for PFS (bevacizumab?+?vorinostat: 44, bevacizumab: 30). Median PFS (3.7 vs 3.9 mo, P?=?0.94, hazard ratio [HR] 0.63 [95% CI: 0.38, 1.06, P?=?0.08]), median OS (7.8 vs 9.3 mo, P?=?0.64, HR 0.93 [95% CI: 0.5, 1.6, P?=?0.79]) and clinical benefit were similar between the 2 arms. Toxicity (grade ?3) in 85 evaluable patients included hypertension (n =?37), neurological changes (n =?2), anorexia (n =?2), infections (n =?9), wound dehiscence (n =?2), deep vein thrombosis/pulmonary embolism (n =?2), and colonic perforation (n =?1).Conclusions
Bevacizumab combined with vorinostat did not yield improvement in PFS or OS or clinical benefit compared with bevacizumab alone or a clinical benefit in adults with recurrent GBM. This trial is the first to test a Bayesian adaptive design with adaptive randomization and Bayesian continuous monitoring in patients with primary brain tumor and demonstrates the feasibility of using complex Bayesian adaptive design in a multicenter setting.
SUBMITTER: Puduvalli VK
PROVIDER: S-EPMC7686463 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
A Bayesian adaptive randomized phase II multicenter trial of bevacizumab with or without vorinostat in adults with recurrent glioblastoma.
Neuro-oncology 20201001 10
<h4>Background</h4>Bevacizumab has promising activity against recurrent glioblastoma (GBM). However, acquired resistance to this agent results in tumor recurrence. We hypothesized that vorinostat, a histone deacetylase (HDAC) inhibitor with anti-angiogenic effects, would prevent acquired resistance to bevacizumab.<h4>Methods</h4>This multicenter phase II trial used a Bayesian adaptive design to randomize patients with recurrent GBM to bevacizumab alone or bevacizumab plus vorinostat with the pri ...[more]