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Updated: Dec 26, 2025
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
A Bayesian adaptive randomized phase II multicenter trial of bevacizumab with or without vorinostat in adults with
Vinay K Puduvalli1, Jing Wu2, Ying Yuan3
1Division of Neuro-Oncoology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
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.
Insights
Vorinostat did not improve outcomes for recurrent glioblastoma patients when combined with bevacizumab. This study tested a novel Bayesian adaptive trial design for brain tumor research.
Area of Science:
- Neuro-oncology
- Clinical trial design
- Pharmacological resistance
Background:
- Bevacizumab shows activity in recurrent glioblastoma (GBM), but resistance often leads to tumor recurrence.
- Vorinostat, a histone deacetylase (HDAC) inhibitor, has anti-angiogenic properties that might overcome bevacizumab resistance.
Purpose of the Study:
- To investigate if vorinostat can prevent acquired resistance to bevacizumab in patients with recurrent GBM.
- To evaluate the efficacy and safety of combining bevacizumab with vorinostat compared to bevacizumab alone.
Main Methods:
- A multicenter phase II trial employed a Bayesian adaptive design with randomization.
- Patients with recurrent GBM received either bevacizumab alone or bevacizumab plus vorinostat.
- Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and clinical outcomes.
Main Results:
- No significant difference in median PFS (3.7 vs 3.9 months) or median OS (7.8 vs 9.3 months) was observed between the two arms.
- Clinical benefit was similar between the bevacizumab monotherapy and combination therapy groups.
- Common grade ≥3 toxicities included hypertension and infections.
Conclusions:
- Combining bevacizumab with vorinostat did not improve PFS, OS, or clinical benefit in recurrent GBM.
- The study successfully demonstrated the feasibility of a complex Bayesian adaptive design in a multicenter brain tumor trial.
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