The combination of circulating Ang1 and Tie2 levels predict progression free survival advantage in Bevacizumab-treated ovarian cancer patients
Menée initialement sur des échantillons sanguins prélevés sur une cohorte de 91 patientes atteintes d'un cancer de l'ovaire, puis validée sur une cohorte complémentaire de 114 patientes, cette étude suggère l'intérêt de mesurer les niveaux plasmatiques de Ang1 et Tie2 pour prédire la réponse au bévacizumab
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.
Clinical Cancer Research , article en libre accès, 2014