Phase III Trial of Bevacizumab Added to Standard Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma: Final Progression-Free Survival and Preliminary Overall Survival Results from AVAglio (PL02.002)

OBJECTIVE: To investigate efficacy and safety of bevacizumab with radiotherapy and temozolomide for newly diagnosed glioblastoma. BACKGROUND: Glioblastoma remains a devastating disease with poor prognosis. Phase II trials suggest bevacizumab may add clinical benefit, with acceptable morbidity. This is the first phase III study evaluating bevacizumab in newly diagnosed glioblastoma. DESIGN/METHODS: In this randomized, double-blind, placebo-controlled trial, patients ≥18 years with newly diagnosed, histologically confirmed glioblastoma received radiotherapy (2Gy 5 days/week, 6 weeks), temozolomide (75mg/m 2 /day) and bevacizumab (10mg/kg) or placebo q2w, followed by 28 days temozolomide free. Patients then received temozolomide for 5 days q4w (150mg/m 2 /day) and bevacizumab (10mg/kg) or placebo q2w (6 cycles). Subsequently, patients received single-agent bevacizumab (15mg/kg) or placebo q3w until progression or unacceptable toxicity. Co-primary endpoints: investigator-assessed progression-free (PFS) and overall survival (OS). Secondary endpoints include independent review facility (IRF)-assessed PFS, safety, health-related quality of life (HRQoL). RESULTS: Baseline characteristics (n=921): 63% male, 40% >60 years, 16%/59%/25% recursive partitioning analysis class III/IV/V, 68% KPS 90–100. The study met its co-primary endpoint of improved PFS (HR 0.64, 95% CI 0.55–0.74, p CONCLUSIONS: The addition of bevacizumab to radiotherapy/temozolomide provided a clinically meaningful and statistically significant PFS improvement associated with stable or improved HRQoL, KPS and diminished steroid requirement. Follow-up to final OS is ongoing. Supported by: F. Hoffmann-La Roche Ltd. Disclosure: Dr. Cloughesy has received personal compensation for activities with Roche, Merck Serono, Genentech, Inc., and Celgene. Dr. Wick has received personal compensation for activities with Roche, MSO, and Eli Lilly & Company. Dr. Wick has received personal compensation in an editorial capacity for CNS Oncology. Dr. Wick has received research support from Boehringer Ingelheim Pharmaceuticals, Inc., Apogenix and Merck Sharp & Dohme Limited. Dr. Mason has received personal compensation for activities with Roche. Professor Henriksson has received personal compensation from Roche Diagnostics Corporation for participation in the AVAglio study. Dr. Saran has received personal compensation for activities with Roche for participation in an advisory board. Dr. Nishikawa has received personal compensation for activities with Roche. Mrs. Hilton has received personal compensation for activities with Roche as an employee. Dr Abrey holds stock or stock options greater than $ 10,000. Dr. Abrey has received personal compensation for activities with Roche as an employee. Dr. Abrey has received personal compensation in an editorial capacity for Current Neurology and Neuroscience Reports. Dr. Abrey holds stock and/or stock options. Dr. Chinot has received personal compensation for activities with Roche Diagnostics Corporation, AstraZeneca Pharmaceuticals, and Merck Sharp & Dohme Limited. Dr. Chinot has received personal compensation in an editorial capacity for Neuro-Oncology and the European Association of NeuroOncology Magazine.