Institute for Cancer Studies, Christie Hospital, University of Manchester, Withington, Manchester, UK.
Curr Opin Oncol. 2013 Sep;25(5):558-65. doi: 10.1097/CCO.0b013e328363e0da.
Angiogenesis has been validated as a target in ovarian cancer through four randomized trials that have reported improved progression-free survival (PFS) in patients with ovarian cancer whose conventional treatment was supplemented with concurrent and maintenance administration of the antivascular endothelial growth factor (VEGF) antibody, bevacizumab. These trials [the International Collaborative Ovarian Neoplasm Group trial (ICON7), the Gynecologic Oncology Group trial (GOG218), OCEANS and AURELIA] have shown that the tumour vasculature is a valid target throughout the lifetime of patients with ovarian cancer. This review seeks to address some of the remaining questions surrounding the optimal strategy for the use of bevacizumab in ovarian cancer.
The first-line trials, ICON7 and GOG218, showed improvements in PFS and in the case of ICON7, an early analysis reported increased overall survival in a predefined group of patients at high risk of disease progression. Trials in recurrent disease, OCEANS and AURELIA, also showed improvements in PFS, raising questions about whether VEGF-inhibiting agents should be confined to first-line therapy, second-line therapy or both.
Both the first-line trials stopped maintenance bevacizumab after 12 and 15 months, respectively; yet, current data suggest that maintenance therapy should continue at least until progression. In addition, current research is focussing on the identification of predictive biomarkers for VEGF inhibitors and candidates have been identified. Thus, the true clinical benefit from VEGF pathway inhibitors in the first-line treatment of ovarian cancer is likely to increase over the next few years.
四项随机试验已经证实血管生成是卵巢癌的一个治疗靶点,这些试验报道称在接受传统治疗的同时联合应用抗血管内皮生长因子(VEGF)抗体贝伐珠单抗进行同期和维持治疗的卵巢癌患者中,无进展生存期(PFS)得到了改善。这些试验[国际卵巢肿瘤协作组试验(ICON7)、妇科肿瘤学组试验(GOG218)、OCEANS 和 AURELIA]表明,肿瘤血管是卵巢癌患者整个生存期的一个有效治疗靶点。本综述旨在探讨在卵巢癌中使用贝伐珠单抗的最佳策略方面仍存在的一些问题。
一线治疗试验 ICON7 和 GOG218 显示 PFS 得到了改善,在 ICON7 的早期分析中,报告称在疾病进展风险高的预定患者亚组中,总生存期得到了早期改善。复发性疾病的试验 OCEANS 和 AURELIA 也显示 PFS 得到了改善,这引发了关于 VEGF 抑制剂是否应仅限于一线治疗、二线治疗或两者都用的问题。
两项一线试验分别在 12 个月和 15 个月后停止了维持贝伐珠单抗治疗;然而,目前的数据表明维持治疗至少应持续到疾病进展。此外,目前的研究重点是确定 VEGF 抑制剂的预测性生物标志物,已经确定了一些候选标志物。因此,VEGF 通路抑制剂在卵巢癌一线治疗中的真正临床获益可能会在未来几年内增加。