OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer

Abstract

Purpose: This randomized, multicenter, blinded, placebo-controlled phase III trial tested the efficacy and safety of bevacizumab (BV) with gemcitabine and carboplatin (GC) compared with GC in platinum-sensitive recurrent ovarian, primary peritoneal, or fallopian tube cancer (ROC).

Patients and methods: Patients with platinum-sensitive ROC (recurrence ≥ 6 months after front-line platinum-based therapy) and measurable disease were randomly assigned to GC plus either BV or placebo (PL) for six to 10 cycles. BV or PL, respectively, was then continued until disease progression. The primary end point was progression-free survival (PFS) by RECIST; secondary end points were objective response rate, duration of response (DOR), overall survival, and safety.

Results: Overall, 484 patients were randomly assigned. PFS for the BV arm was superior to that for the PL arm (hazard ratio [HR], 0.484; 95% CI, 0.388 to 0.605; log-rank P < .0001); median PFS was 12.4 v 8.4 months, respectively. The objective response rate (78.5% v 57.4%; P < .0001) and DOR (10.4 v 7.4 months; HR, 0.534; 95% CI, 0.408 to 0.698) were significantly improved with the addition of BV. No new safety concerns were noted. Grade 3 or higher hypertension (17.4% v < 1%) and proteinuria (8.5% v < 1%) occurred more frequently in the BV arm. The rates of neutropenia and febrile neutropenia were similar in both arms. Two patients in the BV arm experienced GI perforation after study treatment discontinuation.

Conclusion: GC plus BV followed by BV until progression resulted in a statistically significant improvement in PFS compared with GC plus PL in platinum-sensitive ROC.

Fig 1.

CONSORT diagram of all randomly assigned patients (represents intent-to-treat population). BV, bevacizumab; GC, gemcitabine plus carboplatin; PL, placebo. (*) Includes 158 patients with disease progression per RECIST and two patients with clinical disease progression. (†) Includes 100 patients with disease progression per RECIST and four patients with clinical disease progression. (‡) Five patients who were randomly assigned to the GC plus PL arm received one or two doses of BV in error and were assigned to the GC plus BV arm for all safety analyses. Four patients who were randomly assigned to the GC plus PL arm did not receive any protocol treatment and thus were not included in the safety analyses. (§) Five patients who were randomly assigned to the GC plus PL arm received one or two doses of BV in error and were assigned to the GC plus BV arm for all safety analyses.

Fig 2.

Kaplan-Meier estimates of progression-free survival (PFS) based on investigator assessment, censoring for non–protocol-specified therapy (randomly assigned patients). BV, bevacizumab; GC, gemcitabine plus carboplatin; HR, hazard ratio; PL, placebo.

Fig 3.

Progression-free survival (PFS) by baseline risk factor. Vertical dashed line indicates the hazard ratio (HR) for all patients. The diameter of a circle is proportional to the square root of the number of events. BV, bevacizumab; CA-125, cancer antigen 125; ECOG PS, Eastern Cooperative Oncology Group performance status; GC, gemcitabine plus carboplatin; PL, placebo; SLD, sum of longest diameters.

Fig 4.

Kaplan-Meier estimates of progression-free survival (PFS) assessed by independent review committee, censoring for non–protocol-specified cancer therapy (randomly assigned patients). BV, bevacizumab; GC, gemcitabine plus carboplatin; HR, hazard ratio; PL, placebo.