Antiangiogenics in Ovarian Cancer: Where are We Now?

Abstract

ABSTRACT Vascular endothelial growth factor (VEGF) is often over expressed in ovarian cancer (OVCA), promoting ascites and effusions. Preclinical studies of inhibition of VEGF and its receptors (VEGFR) show activity in OVCA xenografts. Clinical interest in evaluating VEGF (R) inhibition was triggered when the Gynecologic Oncology Group demonstrated single agent activity of the VEGF targeted antibody, bevacizumab (BEV) in recurrent OVCA. Since that time, BEV and small molecular VEGFR inhibitors have been studied in numerous phase II and III trials in OVCA. Randomized BEV trials are the most mature with results reported in first line (GOG218, ICON7), platinum sensitive recurrent disease (OCEANS trial) and platinum resistant recurrent disease (AURELIA trial) settings. All trials gave concurrent chemotherapy + BEV with some providing maintenance BEV after chemotherapy. All have shown a biological effect of the addition of BEV with higher response rates and longer progression free survival (PFS) in BEV arms. To date, no trial has shown overall survival (OS) improvement, although mature analyses for OS are awaited. Quality of life data have not suggested a benefit with BEV and toxicity is greater. Results of phase III trials of VEGFR inhibitors cedarinib, pazopanib and nintedanib are awaited. The BEV results lead to several important questions: 1) in the absence of significant OS improvement to date, is there sufficient patient benefit from PFS increases to warrant incorporation of BEV into ovarian cancer treatment? And when over the course of the disease should the agent be given? 2) Is the use of BEV cost effective and affordable? 3) Which patient subset is benefiting most? Subgroup analysis of the ICON7 study, suggests that patients with greater bulk disease (Stage III> 1 cm residual and Stage IV) seem to derive more PFS benefit. Indeed in this subgroup, overall survival also was improved. However, in the GOG0218 trial, the hazard ratio for PFS was observed to be better in patients with Disclosure The author has declared no conflicts of interest.