BACKGROUND The RAINBOW trial showed that second-line ramucirumab with paclitaxel prolongs overall survival (OS) and progression-free survival (PFS) compared with placebo plus paclitaxel for treatment of advanced gastric/gastroesophageal junction cancer. Plasma samples were collected from patients during the trial and tested to identify predictive and prognostic biomarkers. PATIENTS AND METHODS Circulating factors in plasma samples from mutually exclusive subsets of RAINBOW patients were assayed using: Intertek assays (24 markers, 380 samples, 57% of patients) and Lilly-developed assay (LDA) platform (5 markers, 257 samples, 39% of patients). Time-trend plots were generated for each marker from the Intertek assays. Baseline patient data were dichotomized into low- and high-marker subgroups. Markers were analyzed for predictive effects using interaction models and for prognostic effects using main-effects models. RESULTS The Intertek and LDA populations were representative of the full trial population. Plasma levels of VEGF-D and PlGF increased from baseline levels during treatment, then declined after treatment discontinued. Angiopoietin-2 exhibited a decrease during treatment, then increased after treatment discontinuation. No clear time trend was evident with the other markers. Analyses of baseline biomarker expression and its relationship with efficacy variables found no biomarker was predictive for efficacy outcomes, including VEGF-D. However, CRP, HGF, ICAM-3, IL-8, SAA, and VCAM-1 were identified as potential prognostic markers with low baseline levels corresponding to longer OS and PFS. CONCLUSIONS Pharmacodynamic and prognostic relationships were found from the exploratory biomarker analyses in RAINBOW; however, no predictive markers for ramucirumab in gastric cancer were identified in this trial.

中文翻译：

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一项来自RAINBOW的晚期胃癌患者的二线拉莫西鲁单抗的生物标志物分析，一项全球，随机，双盲，3期研究。

背景RAINBOW试验显示，与安慰剂加紫杉醇治疗晚期胃/胃食管交界性癌症相比，含紫杉醇的二线雷莫西单抗可延长总体生存期（OS）和无进展生存期（PFS）。在试验期间从患者中收集血浆样品，并进行测试以鉴定预测性和预后性生物标志物。患者和方法使用以下方法测定了来自彩虹患者互斥子集的血浆样品中的循环因子：Intertek测定（24个标记物，380个样品，占患者的57％）和礼来开发的测定（LDA）平台（5个标记物，257个样品，39个） ％的患者）。从Intertek分析中为每个标记生成了时间趋势图。将基线患者数据分为低和高标记亚组。使用交互模型分析标记物的预测效果，并使用主效应模型分析标志物的预后效果。结果Intertek和LDA人群代表了全部试验人群。VEGF-D和PlGF的血浆水平在治疗期间从基线水平升高，然后在停药后下降。血管生成素-2在治疗期间表现出下降，然后在治疗中断后上升。其他标记物没有明显的时间趋势。基线生物标志物表达及其与功效变量的关系分析发现，没有生物标志物可预测包括VEGF-D在内的功效结果。然而，CRP，HGF，ICAM-3，IL-8，SAA和VCAM-1被确定为潜在的预后指标，基线水平较低，对应于更长的OS和PFS。结论彩虹的探索性生物标志物分析发现了药效学和预后的关系。然而，该试验未发现拉莫西单抗在胃癌中的预测标志物。