Universität zu Köln

Hacker, Ulrich T., Escalona-Espinosa, Laura, Consalvo, Nicola, Goede, Valentin, Schiffmann, Lars, Scherer, Stefan J., Hedge, Priti, Van Cutsem, Eric, Coutelle, Oliver and Buening, Hildegard (2016). Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial. Br. J. Cancer, 114 (8). S. 855 - 863. LONDON: NATURE PUBLISHING GROUP. ISSN 1532-1827

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Abstract

Background: In the phase III AVAGAST trial, the addition of bevacizumab to chemotherapy improved progression-free survival (PFS) but not overall survival (OS) in patients with advanced gastric cancer. We studied the role of Angiopoietin-2 (Ang-2), a key driver of tumour angiogenesis, metastasis and resistance to antiangiogenic treatment, as a biomarker. Methods: Previously untreated, advanced gastric cancer patients were randomly assigned to receive bevacizumab (n = 387) or placebo (n = 387) in combination with chemotherapy. Plasma collected at baseline and at progression was analysed by ELISA. The role of Ang-2 as a prognostic and a predictive biomarker of bevacizumab efficacy was studied using a Cox proportional hazards model. Logistic regression analysis was applied for correlations with metastasis. Results: Median baseline plasma Ang-2 levels were lower in Asian (2143 pg ml(-1)) vs non-Asian patients (3193 pg ml(-1)), P<0.0001. Baseline plasma Ang-2 was identified as an independent prognostic marker for OS but did not predict bevacizumab efficacy alone or in combination with baseline VEGF. Baseline plasma Ang-2 correlated with the frequency of liver metastasis (LM) at any time: Odds ratio per 1000 pg ml(-1) increase: 1.19; 95% CI 1.10-1.29; P<0.0001 (non-Asians) and 1.37; 95% CI 1.13-1.64; P = 0.0010 (Asians). Conclusions: Baseline plasma Ang-2 is a novel prognostic biomarker for OS in advanced gastric cancer strongly associated with LM. Differences in Ang-2 mediated vascular response may, in part, account for outcome differences between Asian and non-Asian patients; however, data have to be further validated. Ang-2 is a promising drug target in gastric cancer.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hacker, Ulrich T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Escalona-Espinosa, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Consalvo, Nicola UNSPECIFIED UNSPECIFIED UNSPECIFIED Goede, Valentin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schiffmann, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherer, Stefan J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hedge, Priti UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Cutsem, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Coutelle, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Buening, Hildegard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-278664
DOI:	10.1038/bjc.2016.30
Journal or Publication Title:	Br. J. Cancer
Volume:	114
Number:	8
Page Range:	S. 855 - 863
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1532-1827
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIAL GROWTH-FACTOR; DOUBLE-BLIND; SERUM ANGIOPOIETIN-2; ANGIOGENIC FACTORS; COLORECTAL-CANCER; 1ST-LINE THERAPY; TUMOR-GROWTH; VEGF-A; METASTASIS; CHEMOTHERAPY Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27866