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- Title
Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab.
- Authors
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; Jayson, Gordon C
- Abstract
<bold>Background: </bold>There is a critical need for predictive/resistance biomarkers for VEGF inhibitors to optimise their use.<bold>Methods: </bold>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.<bold>Results: </bold>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)).<bold>Conclusions: </bold>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.
- Publication
British Journal of Cancer, 2016, Vol 115, Issue 2, p228
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2016.194