Predictive Impact of Circulating Vascular Endothelial Growth Factor in 4 Phase III Trials Evaluating Bevacizumab
A partir des données de 4 essais de phase III évaluant le bevacizumab et incluant au total 1 816 patients atteints d'un cancer colorectal, d'un cancer du poumon ou d'un carcinome à cellules rénales, cette étude évalue, du point de vue de la survie sans progression et de la survie globale, la valeur pronostique des niveaux plasmatiques, mesurés avant traitement, du facteur de croissance VEGF-A en fonction du type de cancer
Purpose:We evaluated the prognostic and predictive utility of circulating vascular endothelial growth factor (VEGF-A) levels in phase III trials of bevacizumab in colorectal cancer, lung cancer, and renal cell carcinoma. Methods:Baseline plasma samples from 1,816 patients were analyzed for VEGF-A using an enzyme-linked immunosorbent assay, which recognizes the major isoforms with equivalent sensitivity. Hazard ratios (HRs) and 95% confidence intervals (CIs) for study end points were estimated using Cox regression analysis. A subset of matched archival tumor samples was analyzed for VEGF-A expression using in situ hybridization. Results:Higher VEGF-A levels showed trends toward adverse prognostic significance in the control arms of multiple trials, reaching statistical significance for overall survival in AVF2107 (highest vs. lowest 50%: HR = 1.76; 95% CI, 1.28-2.41), AVAiL (HR = 1.52; 95% CI, 1.16-2.00), and AVOREN (HR = 1.67; 95% CI, 1.18-2.36). In predictive analyses, the HRs for progression-free survival were similar across low and high VEGF-A subgroups and favored bevacizumab-containing treatment. In the low VEGF-A subgroups, HRs (95% CIs) were 0.61 (0.43-0.87) in AVF2107, 0.71 (0.43-1.16) in E4599, 0.74 (0.59-0.94) in AVAiL (low-dose), 0.89 (0.70-1.13) in AVAiL (high-dose), and 0.56 (0.40-0.78) in AVOREN. Analyses of overall survival data showed similar results. No correlation between primary tumor VEGF-A expression and plasma VEGF-A levels was observed. Conclusions:In this comprehensive evaluation, pretreatment total circulating VEGF-A was prognostic for outcome in metastatic colorectal, lung, and renal cell cancers, but it was not predictive for bevacizumab-based treatment benefit.
Clinical Cancer Research , résumé, 2012