Ovarian cancer accounts for about 3% of cancers among women, but causes more deaths than any other cancer of the female reproductive system. In 2012, an estimated 22,280 new cases of ovarian cancer are expected, and an estimated 15,500 deaths will result from the disease. Because early ovarian cancer has no obvious symptoms, patients often present with disease at the distant stage, which has a five-year survival rate of 27%. This dismal survival rate highlights the need for improved treatments for ovarian cancer and the urgency of the currently emerging therapies for the disease.1
The Antiangiogenesis Agent Bevacizumab
Angiogenesis contributes to the growth and metastasis of solid tumors, and epithelial ovarian-cancer cell lines often express vascular endothelial growth factor (VEGF). When VEGF expression is decreased, tumor vascularization is reduced, and survival is prolonged. Bevacizumab is a humanized monoclonal antibody that binds all isoforms of the VEGF-receptor ligand VEGF-A and decreases tumor vascularization.2 Although bevacizumab is not FDA-approved for the treatment of ovarian cancer, studies have been done with bevacizumab in this patient population and the results have been promisingly positive.
Bevacizumab, for the treatment of ovarian cancer, was described in a Phase 3, double-blind, placebo-controlled trial recently reported by Burger and colleagues in the New England Journal of Medicine.3 When patients with newly diagnosed stage 3 (incompletely resectable) or stage 4 epithelial ovarian cancer received bevacizumab during and up to ten months after paclitaxel and carboplatin, the median progression-free survival (PFS) increased by about four months. Patients who received bevacizumab throughout all 22 cycles of their chemotherapy had a median PFS of 14.1 months, which was longer than the control group (10.3 months) who received chemotherapy with only paclitaxel and carboplatin or the bevacizumab-initiation group (11.2 months) who received bevacizumab only during cycles 2 through 6 of the 22 cycles.
Another Phase 3 trial of bevacizumab randomly assigned women with ovarian cancer to receive carboplatin and paclitaxel every three weeks for six weeks, or this regimen plus bevacizumab given concurrently every three weeks for 5 of 6 cycles and continued for 12 more cycles or until the disease progressed.2 Bevacizumab improved PFS by 2.4 months to 19.8 months (P=0.04) for all patients. In patients at high risk for disease progression, the greatest benefits seen with bevacizumab were both PFS (improved by 5.5 months to 16 months; P=0.002) and overall survival (OS; improved by 7.8 months to 36.6 months; P=0.002).
Based on the positive front-line results, the OCEANS Phase 3 trial tested bevacizumab in patients with platinum-sensitive, recurrent epithelial ovarian cancer.4 The trial enrolled 484 patients, who received chemotherapy every three weeks for 6 cycles with carboplatin plus gemcitabine with either bevacizumab or placebo every three weeks, and subsequently received maintenance with bevacizumab alone or placebo until disease progression or toxicity. The patients who received bevacizumab had a median PFS of 12.4 months, which was 4 months longer than those who received the placebo (PFS=8.4 months; P<0.0001).