Correlation of molecular subtypes with survival in AVAglio (bevacizumab [Bv] and radiotherapy [RT] and temozolomide [T] for newly diagnosed glioblastoma [GB]).

2014 
2001^ Background: Factors that correlate the extent of clinical benefit with anti-VEGF therapy are poorly understood. Two phase 3 trials in newly diagnosed GB (AVAglio and RTOG-0825) reported that Bv+RT/T prolonged PFS but not OS v placebo (P)+RT/T. Specific GB pt subgroups may derive OS benefit from 1st-line Bv; tumor profiling has uncovered intrinsic and prognostic GB molecular subtypes. Bv efficacy in molecular subtypes was evaluated as an exploratory objective in AVAglio. Methods: An 800 gene platform capable of reliable gene expression (GE) measurement in formalin-fixed, paraffin-embedded samples was developed/validated. In AVAglio, randomizedpts (n=921) received: RT/T+Bv or P, 6 wks; 28-day break; maintenance T+Bv or P (x6); Bv or P until PD/unacceptable toxicity. Samples from 342 AVAglio pts (Bv/P; biomarker evaluable population) were profiled and classified into known GB molecular subtypes (pre-defined hypothesis); assigned subtypes were correlated with OS. An exploratory outcome-driven analysis t...
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