OCEANS: A randomized, double-blinded, placebo-controlled phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC).

Abstract

LBA5007 Background: BEV, a humanized anti-VEGF monoclonal antibody, has shown a progression-free survival (PFS) benefit in 2 frontline phase III trials in patients with EOC, PPC and FTC. The therapeutic impact of BEV in combination with carboplatin (C) and gemcitabine (G) followed by single agent BEV to disease progression (PD) was evaluated in this phase III trial in the platinum-sensitive recurrent setting. Methods: Patients had recurrent, platinum-sensitive EOC, PPC or FTC, 1 prior regimen, no prior BEV, ECOG performance status 0-1, measurable disease. Subjects were randomized to: Arm A: [IV C (AUC 4, Day (D) 1) + G (1,000 mg/m2 D1 and 8) + placebo (PL) D1] q21D x 6 cycles (c) → PL q21D until PD or unacceptable toxicity (tox) Arm B: [CG + BEV (15 mg/kg) D1] q21D x 6 c → BEV q21D until PD or tox primary endpoint was investigator assessed PFS (RECIST). Secondary endpoints included objective response (OR), overall survival (OS), duration of response and safety. The design provided 80% power to detect a 27% reduction in the hazard of progression or death in Arm B vs A, limiting the overall type I error of 5%. Results: OCEANS enrolled 484 patients (242 per arm) from 4/07 - 1/10, median follow up of 24 months. BEV plus CG followed by single agent BEV to PD significantly increased PFS compared to CG alone (HR=0.484, p<0.0001). OR increased by 21% (p<0.0001). OS data is immature with only 29% of patients having had an event. The safety profile was consistent with other BEV trials. Conclusions: Results show a statistically significant and clinically relevant benefit when bevacizumab is added to chemotherapy in patients with recurrent, platinum sensitive EOC, PPC, and FTC. This is the first phase III trial of an antiangiogenic to demonstrate a clinical benefit to these patients. [Table: see text]