Molecular Predictors May ID Patients with Glioblastoma Likely to Benefit from Bevacizumab

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Intra-arterial Chemo Beneficial for Recurrent Glioblastoma
Molecular Predictors May ID Patients with Glioblastoma Likely to Benefit from Bevacizumab

CHICAGO, IL—A subgroup of patients newly diagnosed with glioblastoma may derive an overall survival (OS) benefit from bevacizumab, according to exploratory data from the phase 3 AVAglio study reported at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.

Specifically, a significant OS extension was found for patients with isocitrate dehydrogenase 1 (IDH1) wild-type proneural tumors, said Heidi Phillips, PhD, Genentech Inc., South San Francisco, CA. “The predictive value of the proneural subtype should be validated in an independent dataset,” she added.

The investigators identified candidate molecular predictors from samples of patients enrolled in AVAglio, which randomly assigned 921 patients to receive radiotherapy (RT)/temozolomide plus bevacizumab or placebo for 6 weeks followed by a 28-day break, then maintenance temozolomide plus bevacizumab or placebo for six cycles, then bevacizumab or placebo alone until disease progression or unacceptable toxicity.

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Previously, results of both the AVAglio and RTOG-0825 trials reported that patients treated with bevacizumab plus RT/temozolomide prolonged progression-free survival, but not OS, compared with placebo plus RT/temozolomide. However, tumor profiling, which “has uncovered intrinsic and prognostic glioblastoma molecular subtypes,” suggests that specific subgroups of patients with glioblastoma may derive an OS benefit.

“Factors that correlate the extent of clinical benefit with anti-VEGF [vascular endothelial growth factor] therapy are poorly understood,” noted Dr. Phillips, in explaining the rationale for the study.

For this analysis, the investigators developed and validated an 800-gene platform to measure gene expression in formalin-fixed, paraffin-embedded samples. The biomarker evaluable population comprised samples from 342 patients from both the bevacizumab and placebo arms. These samples were profiled and classified into known glioblastoma molecular subtypes, according to the predefined hypothesis; assigned subtypes were then correlated with OS.

“An exploratory outcome-driven analysis to discover novel predictor subtypes more directly associated with OS benefit from bevacizumab was then performed,” she said.

They found that among patients with the IDH1 wild-type proneural tumors, OS was 17.1 months for those in the bevacizumab arm versus 12.2 months for the combination therapy–alone arm (hazard ratio [HR], 0.42; 95% CI: 0.24-0.72; P = 0.002).

“In patients with mesenchymal or proliferative tumors, there was no evidence of a significant OS benefit, nor was there a detrimental effect of bevacizumab,” Dr. Phillips said.

“Patient groups predicted to derive bevacizumab benefit in the outcome-driven method overlapped with, but were not identical to, groups defined by known glioblastoma subtypes; thus, novel OS-associated candidate predictors may more precisely identify patients likely to derive benefit from bevacizumab,” she concluded.

Reference

  1. Phillips H, Sandmann T, Li C et al. Abstract 2001. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.
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