Angiogenesis as a target for the treatment of ovarian cancer

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.