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:
CreatorsEmailORCIDORCID Put Code
Hacker, Ulrich T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Escalona-Espinosa, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Consalvo, NicolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goede, ValentinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schiffmann, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scherer, Stefan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hedge, PritiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Cutsem, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coutelle, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buening, HildegardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
ENDOTHELIAL GROWTH-FACTOR; DOUBLE-BLIND; SERUM ANGIOPOIETIN-2; ANGIOGENIC FACTORS; COLORECTAL-CANCER; 1ST-LINE THERAPY; TUMOR-GROWTH; VEGF-A; METASTASIS; CHEMOTHERAPYMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27866

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