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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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, 19.2–48.5) 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 ≥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. CONCLUSION: Single-agent bevacizumab provides clinical benefit for Japanese patients with recurrent glioblastoma.