Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review

Abstract

As increased angiogenesis has been linked with the progression of ovarian cancer, a number of anti-angiogenic agents have been investigated, or are currently in development, as potential treatment options for patients with advanced disease. Bevacizumab, a recombinant monoclonal antibody against vascular endothelial growth factor, has gained European Medicines Agency approval for the front-line treatment of advanced epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer in combination with carboplatin and paclitaxel, and for the treatment of first recurrence of platinum-sensitive ovarian cancer in combination with carboplatin and gemcitabine. We conducted a systematic literature review to identify available efficacy and safety data for bevacizumab in ovarian cancer as well as for newer anti-angiogenic agents in development. We analyzed published data from randomized, controlled phase II/III clinical trials enrolling women with ovarian cancer to receive treatment with bevacizumab. We also reviewed available data for emerging anti-angiogenic agents currently in phase II/III development, including trebananib, aflibercept, nintedanib, cediranib, imatinib, pazopanib, sorafenib and sunitinib. Significant efficacy gains were achieved with the addition of bevacizumab to standard chemotherapy in four randomized, double-blind, phase III trials, both as front-line treatment (GOG-0218 and ICON7) and in patients with recurrent disease (OCEANS and AURELIA). The type and frequency of bevacizumab-related adverse events was as expected in these studies based on published data. Promising efficacy data have been published for a number of emerging anti-angiogenic agents in phase III development for advanced ovarian cancer. Further research is needed to identify predictive or prognostic markers of response to bevacizumab in order to optimize patient selection and treatment benefit. Data from phase III trials of newer anti-angiogenic agents in ovarian cancer are awaited.

Keywords: Angiogenesis; Bevacizumab; Fallopian tube cancer; Ovarian cancer; Primary peritoneal cancer; Targeted therapies.

Figure 1

GOG-0218 randomized, double-blind, placebo-controlled phase III trial: (A) study design; (B) progression-free survival analysis (reproduced with permission) [21]. EOC = epithelial ovarian cancer. PPC = primary peritoneal cancer. FTC = fallopian tube cancer. C = Carboplatin. AUC = area under the curve. P = Paclitaxel. GOG = Gynecologic Oncology Group. Bev = bevacizumab. q3w = once every 3 weeks.

Figure 2

ICON7 randomized, double-blind, placebo-controlled phase III trial: (A) study design (B) Updated progression-free survival analysis (reproduced with permission) [[22]]. EOC = epithelial ovarian cancer. PPC = primary peritoneal cancer. FTC = fallopian tube cancer. C = Carboplatin. AUC = area under the curve. P = Paclitaxel. Bev = bevacizumab. CGIG = Gynecologic Cancer InterGroup. q3w = once every 3 weeks.