Vesalius Research Center, VIB, Herestraat 49, bus 912, Leuven, Belgium.
J Clin Oncol. 2013 Mar 20;31(9):1219-30. doi: 10.1200/JCO.2012.46.2762. Epub 2013 Feb 11.
Bevacizumab is the first antiangiogenic therapy proven to slow metastatic disease progression in patients with cancer. Although it has changed clinical practice, some patients do not respond or gradually develop resistance, resulting in rather modest gains in terms of overall survival. A major challenge is to develop robust biomarkers that can guide selection of patients for whom bevacizumab therapy is most beneficial. Here, we discuss recent progress in finding such markers, including the first results from randomized phase III clinical trials evaluating the efficacy of bevacizumab in combination with comprehensive biomarker analyses. In particular, these studies suggest that circulating levels of short vascular endothelial growth factor A (VEGF-A) isoforms, expression of neuropilin-1 and VEGF receptor 1 in tumors or plasma, and genetic variants in VEGFA or its receptors are strong biomarker candidates. The current challenge is to expand this first set of markers and to validate it and implement it into clinical practice. A first prospective biomarker study known as MERiDiAN, which will treat patients stratified for circulating levels of short VEGF-A isoforms with bevacizumab and paclitaxel, is planned and will hopefully provide us with new directions on how to treat patients more efficiently.
贝伐珠单抗是首个被证实能延缓癌症患者转移性疾病进展的抗血管生成治疗药物。虽然它改变了临床实践，但一些患者没有响应或逐渐产生耐药性，导致总体生存获益相当有限。一个主要的挑战是开发强大的生物标志物，以指导选择最受益于贝伐珠单抗治疗的患者。在这里，我们讨论了寻找此类标志物的最新进展，包括评估贝伐珠单抗联合全面生物标志物分析疗效的随机 III 期临床试验的首批结果。特别是，这些研究表明，循环短血管内皮生长因子 A（VEGF-A）亚型水平、肿瘤或血浆中神经纤毛蛋白-1 和 VEGF 受体 1 的表达以及 VEGFA 或其受体的遗传变异是强有力的生物标志物候选物。当前的挑战是扩大这一组标志物，并对其进行验证和实施到临床实践中。一项名为 MERiDiAN 的前瞻性生物标志物研究计划对接受贝伐珠单抗和紫杉醇治疗的患者进行循环短 VEGF-A 亚型水平分层，有望为我们提供如何更有效地治疗患者的新方向。
