Abstract
BACKGROUND: This was the first large-scale prospective observational Japanese study evaluating the safety and efficacy of bevacizumab combined with paclitaxel and carboplatin for newly diagnosed advanced ovarian cancer. METHODS: Patients were prospectively enrolled in the primary analysis cohort if they had Stage III or IV epithelial ovarian/fallopian tube/primary peritoneal cancer and were scheduled to receive paclitaxel plus carboplatin every 3 weeks in Cycles 1-6 and bevacizumab every 3 weeks in Cycles 2-22. Primary endpoints were bevacizumab-specific adverse events and adverse events ≥ Grade 3. Secondary endpoints were progression-free survival (PFS) and the response rate. RESULTS: Among 346 patients enrolled, 293 patients formed the primary analysis cohort. Regarding bevacizumab-specific adverse events ≥ grade 3, incidence rates of thromboembolic events (1.4%), gastrointestinal perforation (0.3%), fistula (0.7%), wound dehiscence (0%), and bleeding (0%) were very low. While incidence rates of hypertension (23.2%) and proteinuria (12.6%) were high, all such events were tolerable. No patient with prior bowel resection developed perforation or fistula. Median PFS was 16.3 months (95% CI 14.5-18.9). The response rate was 77.5% (95% CI 67.4-85.7). The response rate was 63.6% in patients with clear cell carcinoma, which tended to be better than previously reported. The median platinum-free interval was 11.5 months, and the platinum-resistant recurrence rate was 24.5%. CONCLUSIONS: Combining bevacizumab with chemotherapy was tolerable and efficacy was acceptable in Japanese patients with advanced epithelial ovarian cancer. Bevacizumab seems to reduce platinum-resistant recurrence and is promising for clear cell carcinoma.