ST LOUIS (MD Consult) - On May 5, 2009, Genentech, Inc, announced that the US Food and Drug Administration (FDA) granted accelerated approval of Avastin (bevacizumab) for the treatment of glioblastoma in persons with progressive disease following prior therapy. The effectiveness of Avastin in this aggressive form of brain cancer was determined on the basis of an improvement in objective response rate observed in some clinical trials. However, no data are currently available from randomized controlled trials demonstrating an improvement in disease-related symptoms or increased survival with Avastin in glioblastoma. In the near future, Genentech expects to begin enrollment in a phase 3 trial for patients with newly diagnosed glioblastoma to further evaluate Avastin in this setting.
The accelerated FDA approval was granted on the basis of independently reviewed data from an open-label, multicenter, noncomparative phase 2 study that included 167 patients with glioblastoma whose cancer had progressed after initial treatment with temozolomide and radiation. Patients in the study were randomly assigned to 2 arms: Avastin alone or Avastin in combination with irinotecan. A primary end point of the study was objective response rate. Response was assessed using magnetic resonance imaging and measured using World Health Organization radiographic criteria along with decreased or stable corticosteroid use.
The median age of patients in this phase 2 study who were treated with Avastin alone was 54 years. Additionally, 32% were female, 81% were in first relapse, 45% had a Karnofsky performance status (KPS) score of 90 to 100, and 55% had a KPS score of 70 to 80. Patients with active brain hemorrhage were excluded from the study. In the trial, safety in this patient population was consistent with Avastin experience in other tumor types. According to an FDA analysis of the study, tumor responses were observed in 26% (95% confidence interval [CI],17.0%-36.1%) of the 85 patients treated with Avastin alone, and the median duration of response in these patients was 4.2 months (95% CI, 3.0-5.7 months).
The efficacy of Avastin in glioblastoma that has progressed following prior therapy is also supported by results from another study that used the same response assessment criteria as detailed for the previously mentioned study. In this single-arm study, 56 patients were treated with Avastin alone. Responses were observed in 20% of patients (95% CI, 10.9%-31.3%), and the median duration of response was 3.9 months (95% CI, 2.4-17.4 months). In this study, Avastin was discontinued as a result of adverse events in 5% of patients. The most frequently reported adverse events were infection (55%), fatigue (45%), headache (37%), hypertension (30%), diarrhea (21%), and epistaxis (19%). Two deaths occurred in the study.
Avastin is a biologic antibody designed to specifically inhibit the vascular endothelial growth factor (VEGF) protein that plays an important role in the development and maintenance of blood vessels, a process known as angiogenesis. Glioblastomas express high levels of VEGF and develop an extensive network of tumor blood vessels. VEGF is a potent activator of angiogenesis throughout the lifecycle of a tumor and is thought to be critical to a tumor's ability to grow and metastasize.
