Recently announced results of the phase III AVAglio study showed that bevacizumab (Avastin) in combination with radiation and temozolomide chemotherapy increased progression-free survival (a co-primary endpoint) by 36% compared to radiation and temozolomide chemotherapy plus placebo (hazard ratio [HR] = 0.64; P < .0001) in people with newly diagnosed glioblastoma. The data were presented at the 17th Annual Meeting of the Society for Neuro-Oncology in Washington, DC.1
Key Findings
The interim results for overall survival, the other co-primary endpoint, did not reach statistical significance (HR = 0.89; P = .2135). Final data on overall survival are expected in 2013.
A 4.4-month improvement in median progression-free survival was observed when people with newly diagnosed glioblastoma received bevacizumab in combination with radiation and chemotherapy, compared to those who received radiation and chemotherapy plus placebo (10.6 vs 6.2 months, respectively).
Safety Data
No new safety findings were observed in the AVAglio study, and adverse events were consistent with those seen in previous trials of bevacizumab across tumor types for approved indications. Adverse events of all grades that occurred more often in the bevacizumab arm compared to the radiation/chemotherapy arm (> 2% increased incidence) included bleeding in mucous/skin linings (26.7% vs 8.9%) or other regions of the body excluding the brain (11.6% vs 8.1%), hypertension (37.5% vs 13%), proteinuria (14% vs 4%), and arterial thromboembolism (5.0% vs 1.6%).
AVAglio is a phase III, randomized, double-blind, placebo controlled trial that assessed the efficacy and safety profile of bevacizumab in combination with radiation and temozolomide chemotherapy following surgery or biopsy in patients with newly diagnosed glioblastoma. Patients were randomly assigned to receive either:
Bevacizumab plus radiation and temozolomide chemotherapy for 6 weeks followed by a 4-week break. Patients then received bevacizumab and temozolomide for up to six cycles, followed by bevacizumab alone until disease progression.
Radiation, temozolomide, and placebo for 6 weeks followed by a 4-week break. Patients then received temozolomide and placebo for up to six cycles, followed by placebo until disease progression.
By meeting its co-primary endpoint of progression-free survival, AVAglio is the first positive phase III study in newly diagnosed glioblastoma since 2005.
Among other indications, bevacizumab is currently approved in the United States under the FDA’s accelerated approval program as a monotherapy for the treatment of adults with glioblastoma who have progressive disease following prior therapy. The drug’s effectiveness in this setting is based on improvement in objective response rate; no data are available from randomized controlled trials demonstrating improvement in disease-related symptoms or increased survival with bevacizumab in glioblastoma. ■
Reference
1. Chinot O: Phase III trial of bevacizumab added to standard radiotherapy and temozolomide for newly-diagnosed glioblastoma: Mature progression-free survival and preliminary overall survival results in AVAglio. 17th Annual Meeting of the Society for Neuro-Oncology. Plenary Session 5. Abstract OT-03. Presented November 17, 2012.
