Guy's and St. Thomas' Hospital, NHS Foundation Trust, Westminster Bridge Road, London SE1 7EH, United Kingdom.
Cancer Treat Rev. 2012 Aug;38(5):484-93. doi: 10.1016/j.ctrv.2011.12.008. Epub 2012 Jan 20.
Aflibercept, also known as vascular endothelial growth factor (VEGF)-Trap, is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting not only all forms of VEGF-A, but also VEGF-B and placental growth factor. It inhibits VEGF-induced angiogenesis in preclinical models. In tumor models, aflibercept is associated with the reduction of tumor vasculature and size, and the inhibition of ascites formation. Clinical studies are investigating the use of aflibercept alone and in combination with other antineoplastic therapies for the treatment of various cancers. Phase I and II studies have provided proof of principle, and support the continuing clinical investigation of aflibercept. Results from the phase III study, VITAL, of aflibercept in the second-line setting in patients with advanced non-small cell lung cancer [NCT00532155] demonstrated efficacy in progression-free survival and overall objective response rate, but overall survival was not significantly improved. A full report awaits publication. The Phase III VANILLA trial in metastatic pancreatic cancer [NCT00574275] showed no improvement in overall survival. Most recently, the phase III VELOUR study [NCT00561470] of aflibercept plus FOLFIRI compared with placebo plus FOLFIRI in patients with metastatic colorectal cancer following failure of an oxaliplatin regimen showed significant improvements in overall survival, progression-free survival, and response rate and the complete results have been submitted to a peer-reviewed journal. This review summarizes preclinical and clinical data for aflibercept and discusses future directions and clinical trials for this agent.
阿柏西普，又称血管内皮生长因子（VEGF）陷阱，是一种重组的诱饵受体融合蛋白，通过靶向不仅所有形式的 VEGF-A，而且还靶向 VEGF-B 和胎盘生长因子，被合理设计用于阻断血管生成。它在临床前模型中抑制 VEGF 诱导的血管生成。在肿瘤模型中，阿柏西普与减少肿瘤血管生成和肿瘤大小以及抑制腹水形成有关。临床研究正在调查单独使用和与其他抗肿瘤疗法联合使用阿柏西普治疗各种癌症。I 期和 II 期研究提供了原理证明，并支持继续进行阿柏西普的临床研究。在晚期非小细胞肺癌二线治疗中的 III 期 VITAL 研究中，阿柏西普的结果在无进展生存期和总客观缓解率方面显示出疗效，但总生存期没有显著改善。完整报告有待发表。转移性胰腺癌的 III 期 VANILLA 试验[NCT00574275]显示总生存期没有改善。最近，III 期 VELOUR 研究[NCT00561470]显示，在奥沙利铂方案失败后的转移性结直肠癌患者中，阿柏西普联合 FOLFIRI 与安慰剂联合 FOLFIRI 相比，总生存期、无进展生存期和缓解率均有显著改善，完整结果已提交给同行评议期刊。这篇综述总结了阿柏西普的临床前和临床数据，并讨论了该药物的未来方向和临床试验。
