Hacker Ulrich T, Escalona-Espinosa Laura, Consalvo Nicola, Goede Valentin, Schiffmann Lars, Scherer Stefan J, Hedge Priti, Van Cutsem Eric, Coutelle Oliver, Büning Hildegard
University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Liebigstr. 20, Leipzig 04103, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Br J Cancer. 2016 Apr 12;114(8):855-62. doi: 10.1038/bjc.2016.30. Epub 2016 Mar 31.
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.
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.
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).
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.
在III期AVAGAST试验中，对于晚期胃癌患者，在化疗基础上加用贝伐单抗可改善无进展生存期（PFS），但未改善总生存期（OS）。我们研究了血管生成素-2（Ang-2）作为生物标志物的作用，Ang-2是肿瘤血管生成、转移及抗血管生成治疗耐药的关键驱动因素。
将先前未接受治疗的晚期胃癌患者随机分为接受贝伐单抗（n = 387）或安慰剂（n = 387）联合化疗。采用酶联免疫吸附测定法（ELISA）分析基线期和病情进展时采集的血浆。使用Cox比例风险模型研究Ang-2作为贝伐单抗疗效的预后和预测生物标志物的作用。应用逻辑回归分析研究与转移的相关性。
亚洲患者（2143 pg/ml）基线期血浆Ang-2水平中位数低于非亚洲患者（3193 pg/ml），P<0.0001。基线期血浆Ang-2被确定为OS的独立预后标志物，但不能单独或联合基线期血管内皮生长因子（VEGF）预测贝伐单抗疗效。基线期血浆Ang-2与任何时间的肝转移（LM）频率相关：每增加1000 pg/ml的比值比为1.19；95%置信区间为1.10 - 1.29；P<0.0001（非亚洲人），以及1.37；95%置信区间为1.13 - 1.64；P = 0.0010（亚洲人）。
基线期血浆Ang-2是晚期胃癌OS的一种新型预后生物标志物，与LM密切相关。Ang-2介导的血管反应差异可能部分解释了亚洲和非亚洲患者之间的结局差异；然而，数据仍需进一步验证。Ang-2是胃癌中一个有前景的药物靶点。
