The Phase III, international study (RTOG 0825) was a collaboration of three cooperative groups: RTOG, NCCTG and ECOG. The randomized, double-blind, placebo-controlled study registered 978 and enrolled 637 patients, respectively, all of whom were newly diagnosed with glioblastoma.
Participants underwent surgery to resect some or most of the tumor, received the standard of care of chemoradiation with temozolomide, and were randomized to receive either bevacizumab or placebo. The study was designed with two primary endpoints: PFS and overall survival OS.
Two distinguishing factors of the study design include: crossover to bevacizumab in the placebo arm at the time of progression, and longitudinal assessment of symptom burden, neurocognitive function and quality of life.
"With the crossover, we could determine the possible overall, or progression-free survival benefits that could distinguish the potential benefits of early versus later use of bevacizumab," Gilbert said. "Also, there may be some alternative advantages for delaying progression in the disease. In order to interpret that possible delay in progression, it was important to understand what the quality of the survival of that possible progression free survival interval."
A third distinction: the study was designed to look at the impact of pre-specified molecular markers -- a nine-gene signature expression and MGMT methylation -- to determine if a subgroup that specifically benefited from bevacizumab could be identified.
The researchers found no difference in OS between the bevacizumab and placebo arms, 15.7 and 16.1 months, respectively. PFS did not reach the pre-set level statistical significance -- although longer in those taking bevacizumab upfront (10.7 months), compared to i
|Contact: Laura Sussman|
University of Texas M. D. Anderson Cancer Center