The Role of Bevacizumab in Advanced Epithelial Ovarian Cancer

Judith      R. Kroep; Johan      W.R. Nortier

doi:10.2174/138161212802002689

Abstract

Background: There is a strong rationale for usage of anti-angiogenic agents in epithelial ovarian cancer. Bevacizumab is the most widely investigated anti-VEGF agent and has shown promising results in recent clinical trials.

Objective: To review the rationale and usage of bevacizumab in advanced epithelial ovarian cancer; as mono-therapy, in combination with chemotherapy both as first line and for recurrent ovarian cancer as well as in combination with other targeted therapies.

Results: In epithelial ovarian cancer, angiogenesis promotes tumor growth, ascites formation and metastasis. Targeting VEGF in ovarian cancer patients may have indirect and direct cytotoxic effects.

Results of placebo controlled phase III trials, the GOG-218 and ICON7, of carboplatin-paclitaxel alone or combined with bevacizumab in chemo-naive patients and the OCEAN trial comparing carboplatin-gemcitabine with or without bevacizumab in women with recurrent platinum-sensitive epithelial ovarian cancer all suggest a benefit for the addition of bevacizumab on progression free survival. Additionally, bevacizumab in combination with other targeted therapies, such as sorafenib and everolimus are under investigation in phase II trials and the current knowledge of molecular predictors is discussed. In Conclusion: Until now no survival benefit has been observed, but bevacizumab is the first anti-angiogenic agent demonstrating a progression free survival benefit in addition to standard chemotherapy regimens in advanced epithelial ovarian cancer, both in the upfront and recurrent setting. Mature overall survival data and the search for predictive biomarkers are important for the future role of bevacizumab in epithelial ovarian cancer.

Keywords: Ovarian cancer, bevacizumab, angiogenesis, VEGF, chemotherapy, anti-VEGF agent, clinical trials, mono-therapy, metastasis, placebo controlled phase III trials.