Bevacizumab with dose-dense paclitaxel/carboplatin as first-line chemotherapy for advanced ovarian cancer

Phase III trials have shown improved survival in ovarian cancer patients when the anti-vascular endothelial growth factor (VEGF) therapy bevacizumab is added to first-line chemotherapy. However, further evidence is needed regarding bevacizumab when used with dose-dense paclitaxel/carboplatin chemotherapy in advanced ovarian cancer patients. This single-arm trial enrolled 184 advanced-stage (III-IV) epithelial ovarian cancer patients following primary debulking. Enrollees were treated with dose-dense paclitaxel/carboplatin chemotherapy with bevacizumab administered on the first day of cycles 2 through 6. Thereafter, maintenance bevacizumab was continued for 12 months in patients exhibiting persistent disease. The primary endpoint was the tumor response rate. The secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse effects. VEGF-associated serum markers and VEGFA/B lymphoma Mo-MLV insertion region 1 homolog (BMI1) pathway proteins in tumor-derived ovarian epithelial cancer cells were analyzed. Of the enrollees with residual disease that completed at least four cycles, 56.6% had a complete response and 3.7% had a partial response. OS and PFS were significantly different between optimally debulked and suboptimally debulked patients (P < 0.05). The most common grade 3/4 adverse event was neutropenia. Patients with progressive disease showed greater basal serum VEGFA and ovarian VEGFA/BMI1 pathway protein expression relative to patients with stable disease and responsive disease (P < 0.05). In conclusion, bevacizumab plus dosedense paclitaxel/carboplatin shows efficacy and tolerability in advanced ovarian cancer patients, especially in those having received optimal resection. Our evidence also suggests a prognostic relationship between serum VEGFA levels and a worse prognosis in ovarian cancer patients with measurable disease.