Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer

Abstract

BACKGROUNDVascular endothelial growth factor is a key promoter of angiogenesis and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, has shown single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate the addition of bevacizumab to standard front-line therapy. RESULTSOverall, 1873 women were enrolled. The median progression-free survival was 10.3 months in the control group, 11.2 in the bevacizumab-initiation group, and 14.1 in the bevacizumab-throughout group. Relative to control treatment, the hazard ratio for progression or death was 0.908 (95% confidence interval [CI], 0.795 to 1.040; P = 0.16) with bevacizumab initiation and 0.717 (95% CI, 0.625 to 0.824; P<0.001) with bevacizumab throughout. At the time of analysis, 76.3% of patients were alive, with no significant differences in overall survival among the three groups. The rate of hypertension requiring medical therapy was higher in the bevacizumab-initiation group (16.5%) and the bevacizumab-throughout group (22.9%) than in the control group (7.2%). Gastrointestinal-wall disruption requiring medical intervention occurred in 1.2%, 2.8%, and 2.6% of patients in the control group, the bevacizumab-initiation group, and the bevacizumab-throughout group, respectively. CONCLUSIONS

Cancer of the ovary, fallopian tube, and peritoneum

“…Bevacizumab 7.5-15 mg/kg every 3 weeks may be added to these regimens [67,68]. Two studies have reported a modest, but statistically significant increase in progression-free survival in patients receiving maintenance bevacizumab following carboplatin, paclitaxel, and concurrent bevacizumab [67,68].…”

“…Two studies have reported a modest, but statistically significant increase in progression-free survival in patients receiving maintenance bevacizumab following carboplatin, paclitaxel, and concurrent bevacizumab [67,68]. There is no evidence as yet to demonstrate an overall survival benefit, but a subgroup analysis of the International Collaboration on Ovarian Neoplasms 7 (ICON7) trial found that there was an improved median survival (30.3 vs 39.4 months) in patients with suboptimal Stage III and Stage IV [67].…”

Incorporation of anti-angiogenesis therapy in the management of advanced ovarian carcinoma—Mechanistics, review of phase III randomized clinical trials, and regulatory implications

“…(Table 1), bevacizumab (Avastin) was the first anti-angiogenesis agent to be advanced into the phase 3 randomized trial design for advanced EOC. To date, four pivotal trials have been completed, two in the primary setting and two for patients with recurrent disease (Table 2) [57][58][59][60][61][62][63][64][65][66].…”

“…Gynecologic Oncology Group (GOG) protocol 218 was a three-arm placebo-controlled study, with all patients receiving carboplatin and paclitaxel [58]. In the first experimental arm, patients were treated with concurrent bevacizumab (15 mg/kg) followed by placebo maintenance (bevacizumab-initiation), while in the second experimental arm, patients received concurrent and maintenance bevacizumab every 21 days for up to 16 doses (bevacizumab-throughout).…”

Recreational Physical Activity and Risk of Ovarian Cancer: a Meta-analysis

“…Although the molecular etiology about OC was continuously investigated (Samuels et al, 2011;Munksgaard et al, 2012), the overall survival rate of OC was still not improved in the last 20 to 30 years (Vaughan et al, 2011). In Robert's study, the poor prognosis of OC was usually attributed to advanced stage at diagnosis and inadequate chemotherapy (Burger et al, 2011), but it was difficult to solve these technical problems. Therefore, the prevention of OC seems to be particularly important.…”