1. Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab.
- Author
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Zhou, Cong, Clamp, Andrew, Backen, Alison, Berzuini, Carlo, Renehan, Andrew, Banks, Rosamonde E, Kaplan, Richard, Scherer, Stefan J, Kristensen, Gunnar B, Pujade-Lauraine, Eric, Dive, Caroline, and Jayson, Gordon C
- Abstract
Background: There is a critical need for predictive/resistance biomarkers for VEGF inhibitors to optimise their use.Methods: Blood samples were collected during and following treatment and, where appropriate, upon progression from ovarian cancer patients in ICON7, a randomised phase III trial of carboplatin and paclitaxel with or without bevacizumab. Plasma concentrations of 15 circulating angio-biomarkers were measured using a validated multiplex ELISA, analysed through a novel network analysis and their relevance to the PFS then determined.Results: Samples (n=650) were analysed from 92 patients. Bevacizumab induced correlative relationships between Ang1 and Tie2 plasma concentrations, which reduced after initiation of treatment and remained decreased until progressive disease occurred. A 50% increase from the nadir in the concentration of circulating Tie2 (or the product of circulating Ang1 and Tie2) predicted tumour progression. Combining Tie2 with GCIG-defined Ca125 data yielded a significant improvement in the prediction of progressive disease in patients receiving bevacizumab in comparison with Ca125 alone (74.1% vs 47.3%, P<1 × 10(-9)).Conclusions: Tie2 is a vascular progression marker for bevacizumab-treated ovarian cancer patients. Tie2 in combination with Ca125 provides superior information to clinicians on progressive disease in patients with VEGFi-treated ovarian cancers. [ABSTRACT FROM AUTHOR]- Published
- 2016
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