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Br J Cancer. 2016 Jul 12;115(2):228-35. doi: 10.1038/bjc.2016.194. Epub 2016 Jun 28.

Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab.

Author information

1
Institute of Cancer Sciences, University of Manchester, Manchester, UK.
2
Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
3
Clinical and Experimental Pharmacology Group, CRUK Manchester Institute, University of Manchester, Manchester, UK.
4
Centre for Biostatistics, University of Manchester, Manchester, UK.
5
Clinical and Biomedical Proteomics Group, St James's University Hospital, Cancer Research UK Clinical Centre, University of Leeds, Leeds, UK.
6
MRC Clinical Trials Unit, University College London, London, UK.
7
Novartis/GSK Pharmaceutical Cooperation, East Hanover, NJ, USA.
8
Department of Gynecological Oncology, Oslo University Hospital, Oslo, Norway.
9
Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris, France.

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.

PMID:
27351218
PMCID:
PMC4947705
DOI:
10.1038/bjc.2016.194
[Indexed for MEDLINE]
Free PMC Article

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