Bevacizumab Superior to Placebo in Treating Ovarian Cancer Patients

Chicago—At a median follow-up of 24 months, patients with recurrent platinum-sensitive ovarian cancer who took bevacizumab in combination with chemotherapy had a 52% reduction in the risk of disease progression and a 4-month increase in progression-free survival (PFS) compared with a group that took the same chemotherapy regimen and a placebo, according to results of a phase 3 trial presented in an oral abstract session at the ASCO meeting. Carol Aghajanian, MD, the study’s lead author, said it was too soon to predict bevacizumab’s effectiveness at increasing overall survival (OS) because only 29% of patients had died. The interim analysis showed there was no statistically significant difference in OS between patients taking bevacizumab or placebo. Bevacizumab in combination with other therapies is approved by the US Food and Drug Administration (FDA) to treat colon and rectal cancer, non–small-cell lung cancer, and kidney cancer. In December the FDA announced that it recommended removing approval of bevacizumab for breast cancer. The blinded, placebo-controlled OCEANS (Carboplatin and Gemcitabine plus Bevacizumab in Patients with Platinum-Sensitive Recurrent Ovary, Primary Peritoneal, or Fallopian Tube Carcinoma) trial enrolled 484 patients from April 2007 through January 2010 who had measurable ovarian cancer based on the Response Evaluation Criteria in Solid Tumors. Other eligibility criteria included an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, no prior chemotherapy for recurrent ovarian cancer, and no prior bevacizumab treatment. Patients were randomized in a 1:1 ratio to receive 15 mg/kg of bevacizumab or placebo every 3 weeks until progression. The bevacizumab group had a median of 12 cycles of treatment (range, 1-43) compared with 10 for the placebo group (range, 1-36). Both arms received the same chemotherapy regimen (carboplatin and gemcitabine), with a median of 6 chemotherapy cycles in each group. All patients had computed tomography scans performed every 9 weeks. The baseline characteristics were similar for the 2 groups: median age was approximately 60 years, approximately one third of patients were ≥65 years of age, and approximately 90% were white. As assessed by the researchers, the median PFS was 12.4 months for patients taking bevacizumab compared with 8.4 months for patients receiving placebo (hazard ratio [HR], 0.484; 95% confidence interval [CI], 0.388-0.605; P<.0001). An independent review committee also analyzed the data and calculated the median PFS was 12.3 months in the bevacizumab group compared with 8.6 months in the placebo group (HR, 0.451; 95% CI, 0.351-0.580; P<.0001). Subgroup analyses based on age, platinum-free interval, and baseline ECOG performance status score also found that patients in the bevacizumab group had significantly longer PFS compared with the placebo group. There was a statistically significant improvement in objective response, with 78.5% of patients having significant tumor shrinkage compared with 57.4% in the placebo group (P<.0001). In addition, the tumor shrinkage lasted a median of 10.4 months in the bevacizumab group compared with 7.4 months in the placebo group (HR, 0.534; 95% CI, 0.408-0.698; P<.0001). The median OS in the bevacizumab group was 35.5 months versus 28.8 months in the placebo group (P=.094). Dr. Aghajanian said 32% of patients taking placebo and 26% of patients taking bevacizumab died. She added that the OS results were not yet mature and would be finalized when 353 deaths occur. The interim results presented at the ASCO meeting included 141 deaths (78 in the placebo group and 63 in the bevacizumab group). Dr. Aghajanian said bevacizumab’s “safety profile is encouraging” and consistent with other trials examining the drug. In the OCEANS study, 35% of patients in the bevacizumab group had a serious adverse event compared with 25% of patients in the placebo group.