A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma

Abstract

The purpose of this study was to evaluate the activity of single-agent bevacizumab in patients with recurrent anaplastic glioma and assess correlative advanced imaging parameters. Patients with recurrent anaplastic glioma were treated with bevacizumab 10 mg/kg every 2 weeks. Complete patient evaluations were repeated every 4 weeks. Correlative dynamic contrast-enhanced MR and (18)fluorodeoxyglucose PET imaging studies were obtained to evaluate physiologic changes in tumor and tumor vasculature at time points including baseline, 96 h after the first dose, and after the first 4 weeks of therapy. Median overall survival was 12 months (95% confidence interval [CI]: 6.08-22.8). Median progression-free survival was 2.93 months (95% CI: 2.01-4.93), and 6-month progression-free survival was 20.9% (95% CI: 10.3%-42.5%). Thirteen (43%) patients achieved a partial response. The most common grade ≥ 3 treatment-related toxicities were hypertension, hypophosphatemia, and thromboembolism. Single-agent bevacizumab produces significant radiographic response in patients with recurrent anaplastic glioma but did not meet the 6-month progression-free survival endpoint. Early change in enhancing tumor volume at 4 days after start of therapy was the most significant prognostic factor for overall and progression-free survival.

Fig. 1.

Sample radiographic response by DCE-MRI and FDG PET comparing baseline scans to 4-day (4D) and 4-week (4W) studies across different parameters. Each parameter was evaluated using the median of the top 100 voxels within the area determined by the T1 enhancing tumor volume (ETV) for a given time point. At 4 days, the patient had a 57% reduction in ETV, 56% reduction in K_trans, and 1% reduction in fpv; at 4 weeks compared with baseline, ETV decreased by 89%, K_trans by 84%, fpv by 80%, and PET standard uptake value increased by 11%.

Fig. 2.

Plots show data for all patients sorted by percentage change from baseline to 4W evaluation across imaging parameters: ETV, K_trans, fpv, and FDG PET standard uptake value (SUV). The majority of patients had a decrease in the MRI parameters at 4D and 4W from treatment start, demonstrating vascular permeability and tumor perfusion effects of bevacizumab. The average decrease in FDG PET SUV was small and not significant.

Fig. 3.

The only significant factor in the multivariate analysis was % change of ETV at 4D. Kaplan–Meier estimates for patients with survival above and below the median % change in ETV (−48.6%) were significantly different for both overall survival (P = .0008) and progression-free survival (P = .0296).