Phase II Study of Single-agent Bevacizumab in Japanese Patients with Recurrent Malignant Glioma†

This single-arm, open-label, Phase II study evaluated the efficacy and safety of single-agent bevacizumab, a monoclonal antibody against vascular endothelial growth factor, in Japanese patients with recurrent malignant glioma. Patients with histologically confirmed, measurable glioblastoma or World Health Organization Grade III glioma, previously treated with temozolomide plus radiotherapy, received 10 mg/kg bevacizumab intravenous infusion every 2 weeks. The primary endpoint was 6-month progression-free survival in the patients with recurrent glioblastoma. Of the 31 patients enrolled, 29 (93.5) had glioblastoma and 2 (6.5) had Grade III glioma. Eleven (35.5) patients were receiving corticosteroids at baseline; 17 (54.8) and 14 (45.2) patients had experienced one or two relapses, respectively. The 6-month progression-free survival rate in the 29 patients with recurrent glioblastoma was 33.9 (90 confidence interval, 19.248.5) and the median progression-free survival was 3.3 months. The 1-year survival rate was 34.5 with a median overall survival of 10.5 months. There were eight responders (all partial responses) giving an objective response rate of 27.6. The disease control rate was 79.3. Eight of the 11 patients taking corticosteroids at baseline reduced their dose or discontinued corticosteroids during the study. Bevacizumab was well-tolerated and Grade epsilon 3 adverse events of special interest to bevacizumab were as follows: hypertension [3 (9.7) patients], congestive heart failure [1 (3.2) patient] and venous thromboembolism [1 (3.2) patient]. One asymptomatic Grade 1 cerebral hemorrhage was observed, which resolved without treatment. Single-agent bevacizumab provides clinical benefit for Japanese patients with recurrent glioblastoma.