Carol Aghajanian, MD
Women with recurrent platinum-sensitive ovarian cancer had a 50% improvement in progression-free survival (PFS) when bevacizumab was added to carboplatin/ gemcitabine chemotherapy and continued as maintenance therapy, according to trial data presented in June at the ASCO meeting.
Treatment with the angiogenesis inhibitor was associated with a median PFS of 12.4 months compared with 8.4 months for patients who received chemotherapy alone. Substantially more patients treated with bevacizumab had significant tumor shrinkage, and they had more durable responses.
The addition of bevacizumab “provides a clinically meaningful benefit over chemotherapy alone in recurrent ovarian cancer,” said study lead Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan-Kettering Cancer Center in New York. “The safety data are consistent with the bevacizumab profile. In particular, we observed no gastrointestinal perforations and no new safety signals. This regimen should be considered a new option for recurrent, platinum-sensitive ovarian cancer.”
The findings came from the Ovarian Cancer Education Awareness Network Study (OCEANS), designed to show whether combining 2 active ovarian cancer regimens would lead to better disease control as compared with an active chemotherapy regimen by itself. The trial involved 484 women in first recurrence of platinum-sensitive ovarian cancer. About 60% of the patients had a platinum-free interval in excess of 12 months.
Investigators randomized patients to carboplatin (AUC of 4) and gemcitabine 1000 mg/m2 plus either placebo or concomitant bevacizumab 15 mg/kg followed by bevacizumab monotherapy until disease progression. The primary endpoint was PFS, and the trial was statistically powered to detect a 27% improvement, from 8.6 to 11.8 months. The trial also had sufficient statistical power to detect a 21% improvement in median overall survival (OS), from 18 to 22.8 months.
After a median follow-up of 24 months, the primary analysis showed a 52% reduction in the hazard for progression in the bevacizumab arm (HR 0.48; P
<.0001). Subgroup analysis revealed a similar benefit regardless of platinum-free interval, cytoreductive surgery for recurrent disease, patient age, or baseline performance status.
The bevacizumab-treated patients had an objective response rate of 78.5% compared with 57.4% in the placebo group (P
<.0001). Twice as many patients in the bevacizumab group had complete responses (17% vs 9%). Median duration of response was 10.4 months with bevacizumab and 7.4 months with placebo (P
The safety data are consistent with the bevacizumab profile. In particular, we observed no gastrointestinal perforations and no new safety signals. This regimen should be considered a new option for recurrent, platinum-sensitive ovarian cancer. ”
–Carol Aghajanian, MD
A preliminary survival analysis showed a median OS of 35.5 months in the bevacizumab arm and 29.9 months in the placebo arm, a difference that did not achieve statistical significance. Aghajanian pointed out that the trial had accrued only 29% of survival endpoints at the time of the analysis.
Adverse events were universal in both groups. The bevacizumab arm had a higher rate of serious adverse events (35% vs 25%) and grade 3 to 5 adverse events (90% vs 82%).
Aghajanian C, Finkler NJ, Rutherford T, et al. OCEANS: a randomized, double-blinded, 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. J Clin Oncol. 2011;29(suppl; abstr LBA5007).