A Phase Ii Trial on the Combination of Bevacizumab and Irinotecan in Recurrent Ovarian Cancer.

5564 Background: Irinotecan and bevacizumab have single agent activity in both platinum sensitive and resistant recurrent ovarian cancer. We sought to evaluate the efficacy and safety of the combination in this setting. The primary endpoint is to estimate the progression free survival (PFS) at 6 months. Secondary objectives include overall survival (OS), observed response rate (ORR), duration of response, and toxicity. Methods: Ovarian cancer patients with recurrence after any number of prior regimens were eligible. Irinotecan 250 mg/m2 (amended to 175 mg/m2 after treatment-related toxicities in the first 6 patients) and bevacizumab 15 mg/kg were administered every 3 weeks until disease progression or toxicity. Response was assessed by RECIST every 2 cycles and by CA-125 criteria for those without measurable disease. Results: Of the 29 patients enrolled, 10 were platinum-sensitive and 19 were platinum-resistant. The median number of prior regimens was 5 (range 1-12): 13 patients had prior bevacizumab and 11 patients prior topotecan. The median number of study cycles given was 7 (range 1-34); 5 patients withdrew after 1 cycle (3 due to toxicity). Of the 24 patients assessable for response, 8 patients experienced partial response (PR), 13 maintained stable disease (SD), and 3 had progressive disease; 12 patients with PR/SD were platinum resistant. The ORR was 27.6% (95% CI: 0.127-0.472) and the clinical benefit rate was 72.4% (95% CI: 0.565-0.873) for the intention-to-treat population (n=29). Twelve patients had longer than 6 months of sustained response. Median PFS was 8.1 months (95% CI: 5.1-12.3 months); median OS was 15.9 months (95% CI: 13.4 months- upper bound not reached). The PFS rate at 6 months was 55.2% (95% CI: 0.397-0.766). The most common grade 3/4 toxicities included diarrhea (5 pts), neutropenia (3), hypertension (3), proteinuria (2), fatigue (2), nausea (2), abdominal pain (2), and GI perforation (1). No treatment-related deaths were observed. Conclusions: The combination of irinotecan and bevacizumab showed encouraging activity in heavily-pretreated patients with recurrent ovarian cancer. The median PFS of 8.1 months is comparable to other bevacizumab-containing doublets reported in the AURELIA trial. Clinical trial information: NCT01091259.