CHICAGOBevacizumab + carboplatin/gemcitabine followed by bevacizumab until disease progression provided a clinically meaningful benefit in women with platinum-sensitive recurrent ovarian cancer, representing the first Phase 3 trial of an antiangiogenic agent to demonstrate such a benefit, investigators reported during the American Society of Clinical Oncology’s 2011 Annual Meeting.

The randomized, double-blind, placebo-controlled OCEANS study found that women lived significantly longer and had a 52% reduction in risk of disease progression without additional chemotherapy, Carol Aghajanian, MD, Memorial Sloan-Kettering Cancer Center, New York,  and colleagues reported. “This is good news for women with these cancers, as we are increasingly able to treat ovarian cancer as a chronic disease,” she said.

The multicenter study randomized 484 women with recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer to carboplatin AUC 4 Day 1 + gemcitabine 1000mg/m2 on Days 1 and 8 + bevacizumab 15mg/kg (n=242) or the same chemotherapy regimen + placebo (n=242). Bevacizumab or placebo was continued after the completion of chemotherapy until disease progression or unacceptable toxicity.

Eligibility criteria included measurable disease, ECOG performance status (PS) 0/1, no prior chemotherapy for recurrent ovarian cancer, and no prior bevacizumab therapy. Stratification variables included platinum-free interval (6-12 vs. >12 months) and cytoreductive surgery for recurrent disease (yes or no). Primary study endpoint was investigator assessed progression-free survival (PFS); secondary endpoints included objective response, overall survival (OS), duration of response, and safety.

Baseline characteristics were similar between the groups. Mean age was 61 years (range, 28-86 years) in the chemotherapy alone group and 60 years (range, 38-87 years) in the bevacizumab group. In the chemotherapy alone group, 42% had a platinum-free interval of 6-12 months compared with 41% in the bevacizumab group; this was 58% and 59%, respectively, for platinum-free interval >12 months. Ten percent of women in the chemotherapy alone group had cytoreductive surgery for recurrent disease vs. 125% in the bevacizumab group.

At a median follow-up of 24 months, median PFS was 12.4 months for patients in the bevacizumab group vs. 8.4 months for patients who had chemotherapy alone (HR 0.49 [0.40–0.61; P<0.0001) See Table. Subgroup analyses of PFS found consistency of benefit of bevacizumab across all baseline risk factors, including platinum-free interval, cytoreductive surgery for recurrent disease, age, and baseline ECOG PS.

Objective response rate was statistically significant See Table. for the bevacizumab vs. the chemotherapy alone group and response was of longer duration, 10.4 vs. 7.4 months, respectively (HR 0.534 [0.408–0.698]; P<0.0001). Interim OS at 24 months was 35.5 months for the bevacizumab group vs. 29.9 months for the chemotherapy alone group (HR 0.751 [0.537–1.052]; P=0.094).

The side effects of bevacizumab were consistent with those seen in previous studies. No gastrointestinal perforations were seen in the OCEANS trial.

The investigators said the next step is to evaluate the role of bevacizumab in combination with chemotherapy for platinum-resistant disease, and to combine bevacizumab with other emerging novel therapies, such as PARP inhibitors.

“The data from OCEANS demonstrate a clear response from bevacizumab in these cancers,” Dr. Aghajanian said. “These are very meaningful results for patients for whom there are currently limited treatment options available.”