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The combination of circulating Ang1 and Tie2 levels predict progression free survival advantage in Bevacizumab-treated ovarian cancer patients.
Backen, Alison C Clamp, Andrew R Berzuini, C Zhou, C Oza, A Bannoo, S Scherer, S Banks, R
Backen, Alison C
Clamp, Andrew R
Berzuini, C
Zhou, C
Oza, A
Bannoo, S
Scherer, S
Banks, R
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Abstract
Purpose: Randomized ovarian cancer trials, including ICON7, have reported improved progression-free survival (PFS) when bevacizumab was added to conventional cytotoxic therapy. The improvement was modest prompting the search for predictive biomarkers for bevacizumab. Experimental Design: Pre-treatment training (n = 91) and validation (n = 114) blood samples were provided by ICON7 patients. Plasma concentrations of 15 angio-associated factors were determined using validated multiplex ELISAs. Results: The combined values of circulating Ang1 and Tie2 concentrations predicted improved PFS in bevacizumab-treated patients in the training set. Using median concentrations as cut-offs, high Ang1/low Tie2 values were associated with significantly improved PFS for bevacizumab-treated patients (median: 23.0 months versus 16.2, log rank test, p=0.006). High Ang1/high Tie2 values were associated with a poor outcome for bevacizumab-treated patients (median: 12.8 months versus 28.5 months, log rank test p=0.007). Ang1 and Tie2 jointly interacted with the effect of bevacizumab on PFS (pinteraction=0.003). The prognostic indices derived from the training set differentiated classes of high and low probability for progression in the validation set (p = 0.008). Conclusions: The combined values of Ang1 and Tie2 are predictive biomarkers for improved PFS in bevacizumab-treated patients with ovarian cancer.
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2014-06-19
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Article
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The combination of circulating Ang1 and Tie2 levels predict progression free survival advantage in Bevacizumab-treated ovarian cancer patients. 2014: Clin. Cancer Res.