Tumor Microvessel Density and Outcome With Bevacizumab in Ovarian Cancer
A retrospective biomarker analysis of the phase III GOG-0218 trial indicated a higher tumor microvessel density was associated with progression-free and overall survival benefit with bevacizumab (Avastin) vs placebo plus front-line chemotherapy in patients with ovarian cancer. These findings were reported in the Journal of the National Cancer Institute by Bais et al.
Study Details
In the trial, patients with incompletely resected stage III or IV disease were randomized to receive six cycles of chemotherapy plus either bevacizumab or placebo followed by bevacizumab or placebo. The bevacizumab group had significantly better progression-free survival but not overall survival.
Biomarker Associations
Among the 980 patients in the biomarker evaluable population (79% of the total population), no significant associations with outcome were found for vascular endothelial growth factor (VEGF) receptor-2, neuropilin-1, or MET. Higher tumor microvessel density (above median value), measured as CD31-positive vessels/mm2, was associated with significantly better progression-free survival for bevacizumab vs placebo (hazard ratio [HR] = 0.40, 95% confidence interval [CI] = 0.29–0.54, vs 0.80, 95% CI = 0.59–1.07; P = .003 for interaction) and significantly better overall survival (HR = 0.67, 95% CI = 0.51–0.88, vs 1.10, 95% CI = 0.84–1.44; P = .02 for interaction). Tumor VEGF-A was not predictive for progression-free survival, but high VEGF-A defined as the upper quartile (low = bottom 3 quartiles) was associated with improved overall survival for bevacizumab vs placebo (HR = 0.61, 95% CI = 0.42–0.89, vs 1.00, 95% CI = 0.80–1.23; P = .02 for interaction).
The investigators concluded: “These retrospective tumor biomarker analyses suggest a positive association between density of vascular endothelial cells (the predominant cell type expressing VEGF receptors) and tumor VEGF-A levels and magnitude of bevacizumab effect in ovarian cancer. The potential predictive value of [tumor microvessel density] (CD31) and tumor VEGF-A is consistent with a mechanism of action driven by VEGF-A signaling blockade.”
Carlos Bais, PhD, formerly of Genentech, now of MedImmune, and Michael J. Birrer, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, are the corresponding authors of the Journal of the National Cancer Institute article.
The study was supported by National Cancer Institute grants and by Roche/Genentech.
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