Prognostic Value of Angiopoietin-2 for Death Risk Stratification in Patients with Metastatic Colorectal Carcinoma

Abstract

Background: Baseline prognostic biomarkers stratifying treatment strategies in first-line metastatic colorectal cancer (mCRC) are lacking. Angiopoietin-2 (Ang-2) is proposed as a potential biomarker in several cancers. We therefore decided to establish the additional prognostic value of Ang-2 for overall survival (OS) in patients with first-line mCRC.

Methods: We enrolled 177 patients treated with a bevacizumab containing chemotherapy in two prospective phase II clinical trials. Patient plasma samples were collected at baseline. ELISAs were used to measure Ang-2.

Results: The multivariable Cox model identified increased lactate dehydrogenase [HR, 1.60; 95% confidence interval (CI), 1.04–2.45; P = 0.03] and Ang-2 log-transformation level (HR, 1.59; 95% CI, 1.14–2.21; P = 0.0065) as two significant independent OS prognostic factors. It exhibited good calibration (P = 0.8) and discrimination (C-index: 0.64; 95% CI, 0.58–0.68). Ang-2 parameter inclusion in the GERCOR reference model significantly and strongly improved its discriminative ability because the C-statistic increased significantly from 0.61 to 0.63 (bootstrap mean difference = 0.07; 95% CI, 0.069–0.077). Interestingly, the addition of Ang-2 binary information with a 5 ng/mL cutoff value to the GERCOR model allowed the reclassification of intermediate-risk profile patients (41%) into two subsets of low and high risks.

Conclusions: Our study provides robust evidence in favor of baseline Ang-2 prognostic value for OS adding to the conventional factors. Its assessment appears to be useful for the improvement in risk stratification for patients with intermediate-risk profile.

Impact: Ang-2 ability to predict OS at diagnosis could be of interest in the selection of patients eligible for intermittent or sequential therapeutic strategies dedicated to the optimization of patients' quality of life and chemotherapy cost-effectiveness. Cancer Epidemiol Biomarkers Prev; 24(3); 603–12. ©2015 AACR.