211P - Prognostic value of angiopoietin-2 for overall survival in patients with metastatic colorectal carcinoma treated by chemotherapy and bevacizumab

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Translational Research
Presenter Marine Jary
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors M. Jary1, D. Vernerey2, E. Dobi3, F. Monnien4, Y. Godet5, S. Kim1, O. Bouché6, S. Fratte7, F. Ghiringhelli8, A. Gonçalves9, T. Lecomte10, J. Leger11, L. Queiroz5, O. Adotevi5, F. Bonnetain2, C. Borg12
  • 1Medical Oncology, University Hospital of Besancon, 25030 - Besancon/FR
  • 2Methodological And Quality Of Life In Oncology Unit, Ea 3181, University Hospital of Besançon, 25030 - Besançon/FR
  • 3Medical Oncology, University Hospital J. Minjoz, 25030 - Besancon/FR
  • 4Centre D'investigation Clinique, Cic-bt 506, University Hospital of Besançon, Besançon/FR
  • 5Inserm, Unit 1098, University of Franche Comté, Besançon/FR
  • 6Gastroenterology And Digestive Oncology, Hopital Robert Debré, Reims/FR
  • 7Gastroenterology, Centre Hospitalier Belfort Montbeliard, Belfort/FR
  • 8Oncology, CLCC GF Leclerc, Dijon/FR
  • 9Crcm, Inserm U1068, Cnrs U7258, Aix-Marseille University, Marseille/FR
  • 10Hepato-gastro-enterologie, Hopital Trousseau, 37000 - Tours/FR
  • 11Cic Inserm 202, CHRU de Tours, Tours/FR
  • 12Medical Oncology, University Hospital Besançon, 25030 - Besançon/FR

Abstract

Aim

Angiogenesis is implicated in carcinogenesis and tumor progression. Angiopoietin-2 (Ang-2) is a protein involved in the regulation of vascular remodeling. Its seric level has been proposed asaninterestingbiomarker in mCRC patients. Nowadays, specific prognostic biomarkers helping the clinician to manage its first line treatment strategies are still lacking. We therefore decided to establish the additional prognostic value of Ang-2 for overall survival (OS) in first line metastatic colorectal cancer patients.

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. Enzyme-linked immunosorbent assays (ELISA) were used to measure Ang-2 in plasma samples.

Results

The multivariable Cox model identified that increased LDH (HR = 1.60, 95%CI = 1.04-2.45, p = 0.03) and Ang-2 level (HR = 1.59, 95%CI = 1.14-2.21, p = 0.0065, withlog-transformation) were two significant independentprognostic factors for OS.It exhibited good calibration (p = 0.8) and discrimination (C-statistic 0.64; 95%CI = 0.58-0.68). The inclusion of the Ang-2 parameter in the GERCOR reference model significantly and strongly improved its discriminative ability since the C-statistic increased significantly from 0.61 to 0.63 (bootstrap mean difference = 0.07, 95%CI = 0.069-0.077).Interestingly, using an Ang-2 binary information with a 5 ng/mL cut off value, patients having an intermediate risk profile (41%) were reclassified into two subsets of low and high risks.

Conclusions

Our study provides robust evidence in favour ofAng-2 prognostic value for OSat baseline adding to the conventional factors. Assessment of Ang-2appears to be useful forthe improvement in risk stratification for patients with intermediate risk profile.

Disclosure

All authors have declared no conflicts of interest.