TY - JOUR
T1 - Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab
AU - Zhou, Cong
AU - Clamp, Andrew
AU - Backen, Alison
AU - Berzuini, Carlo
AU - Renehan, Andrew
AU - Banks, Rosamonde E.
AU - Kaplan, Richard
AU - Scherer, Stefan J.
AU - Kristensen, Gunnar B.
AU - Pujade-Lauraine, Eric
AU - Dive, Caroline
AU - Jayson, Gordon C.
PY - 2016/7/12
Y1 - 2016/7/12
N2 - 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-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.
AB - 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-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.
UR - http://www.scopus.com/inward/record.url?scp=84976431460&partnerID=8YFLogxK
U2 - 10.1038/bjc.2016.194
DO - 10.1038/bjc.2016.194
M3 - Article
AN - SCOPUS:84976431460
SN - 0007-0920
VL - 115
SP - 228
EP - 235
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 2
ER -
