Table 2. Paclitaxel/Platinum Combinations Versus Comparator Arms in Trials continued...
GOG-0218 was a double blind, randomized, controlled trial that included 1,873 women with stage III or IV disease, all of whom received chemotherapy—carboplatin (AUC 6) and paclitaxel (175 mg/m2 for six cycles). Participants were randomly assigned to receive:
- Chemotherapy plus placebo (cycles 2 through 22) (i.e., control).
- Chemotherapy plus bevacizumab (15 mg/kg cycles 2 through 6), followed by placebo (cycles 7 through 22) (i.e., bevacizumab initiation).
- Chemotherapy plus bevacizumab (15mg/kg cycles 2 through 22) (i.e., bevacizumab throughout).
The women were enrolled with a primary endpoint of PFS; 40% of the patients had suboptimally resected stage III disease, and 26% had stage IV disease. There was no difference in PFS between the control group and the bevacizumab-initiation group. There was a statistically significant increase in PFS in the bevacizumab-throughout group when compared with the control group (14.1 vs. 10.3 months), with a HR of progression or death of 0.717 in the bevacizumab-throughout group (95% CI, 0.625–0.824; P < .001). Median OS was 39.3, 38.7, and 39.7 months for the control group, bevacizumab-initiation group, and the bevacizumab-throughout group, respectively. Quality of life was not different between the three groups. Hypertension grade 2 or greater was more common with bevacizumab than with the placebo. There were more treatment-related deaths in the bevacizumab-throughout arm (10 of 607, 2.3%) than in the control arm (6 of 601, 1.0%).[Level of evidence: 1iDiii]
ICON 7 randomly assigned 1,528 women after initial surgery to chemotherapy—carboplatin (AUC 5 or 6) plus paclitaxel (175 mg/m2 for six cycles)—or to chemotherapy plus bevacizumab (7.5 mg/kg for six cycles), followed by bevacizumab alone for an additional 12 cycles. The women were randomly assigned, and PFS was the main outcome measure; 9% of patients had early-stage, high-grade tumors, and 70% had stage IIIC or IV disease. Twenty-six percent had more than 1 cm of residual tumor prior to initiating chemotherapy. Median PFS was 17.3 months in the control group and 19 months in the bevacizumab group. HR for progression or death in the bevacizumab group was 0.81 (95% CI, 0.70–0.94; P = .004). Bevacizumab was associated with an increase in bleeding, hypertension (grade 2 or higher), thromboembolic events (grade 3 or higher), and gastrointestinal perforations. Grade 3 or greater adverse events were more common in the bevacizumab group. Quality of life was not different between the two groups.[Level of evidence: 1iiDiii]
A third trial, OCEANS (Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum-Sensitive Recurrent Diseases [NCT00434642]), assessed the role of bevacizumab in the treatment of platinum-sensitive recurrences (see Table 3 for other trials in this setting). In this double-blind, placebo-controlled, phase III trial of chemotherapy (gemcitabine + carboplatin) with or without bevacizumab for recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer, 242 patients were randomly assigned per arm. Median PFS for patients receiving bevacizumab was 12.4 months versus 8.4 months for those receiving a placebo. The effect of bevacizumab on HR to progression in patients assigned to the bevacizumab arm compared with placebo was 0.484 (95% CI, 0.388–0.605; P <.0001). Objective responses to chemotherapy were increased when combined with bevacizumab (78.5% vs. 57.4%; P < .0001).