Addition of Bevacizumab to Ovarian Cancer Treatment is Associated With Better Survival

Addition of Bevacizumab to Ovarian Cancer Treatment is Associated With Better Survival

Two new studies published in the New England Journal of Medicine point to the importance of using bevacizumab in the treatment of ovarian cancer. Bevacizumab, a recombinant humanized monoclonal antibody directed against the vascular endothelial growth factor, has shown single-agent activity in women with recurrent tumors. Bevacizumab is currently used in the treatment of colorectal, renal cell, and other cancers.

In the first study, Dr Timothy J. Perren, consultant medical oncologist at the St. James’s Institute of Oncology, St. James’s University Hospital in the United Kingdom, and colleagues randomly assigned 1,528 women from 11 countries to carboplatin and paclitaxel given every 3 weeks for 6 cycles or to carboplatin and paclitaxel plus bevacizumab (7.5 mg per kilogram of body weight) given concurrently every three weeks for five or six cycles and continued for 12 additional cycles or until progression of disease. Perren et al. found progression-free survival at 36 months was 20.3 months (restricted mean) with standard therapy, as compared with 21.8 months with standard therapy plus bevacizumab; they calculated a 0.81 hazard ratio for progression or death with bevacizumab added. However, they noted that bevacizumab was associated with more toxic effects.

Patients at high risk for progression also benefited from the addition of bevacizumab. In this group, Perren and colleagues found that progression-free survival at 42 months was 18.1 months (restricted mean) for patients receiving bevacizumab, compared to 14.5 months in the group just receiving carboplatin and paclitaxel. Median overall survival for the regimen with bevacizumab and the regimen without bevacizumab was 36.6 and 28.8, respectively.

“Bevacizumab improved progression-free survival in women with ovarian cancer,” they concluded. “The benefits with respect to both progression-free and overall survival were greater among those at high risk for disease progression.”

Meanwhile, Dr Robert A. Burger, gynecologic oncologist at Fox Chase Cancer Center, and colleagues conducted a double-blind, placebo-controlled, phase 3 trial of 1,873 women. The women had newly diagnosed stage III (incompletely resectable) or stage IV epithelial ovarian cancer and had undergone debulking surgery. All patients received chemotherapy consisting of intravenous paclitaxel at a dose of 175 mg per square meter of body-surface area, plus carboplatin at an area under the curve of 6, for cycles 1 through 6. The women were also randomly assigned to one of three study treatments for cycles 2 through 22, each cycle of 3 weeks’ duration: a control group also received placebo in cycles 2 through 22; a bevacizumab initiation group received bevacizumab (15 mg per kilogram of body weight) added in cycles 2 through 6 and placebo added in cycles 7 through 22; a third group received bevacizumab in cycles 2 through 22.

Burger et al. found the greatest median progression-free survival in the group that received bevacizumab throughout the study, with median progression-free survival was 14.1 months, 11.2 months, and 10.3 months in the bevacizumab throughout group, bevacizumab-initiation group, and control group, respectively. Hypertension and gastrointestinal-wall disruption requiring medical intervention were reported among all the groups, but the groups receiving bevacizumab (either throughout or initiation) had higher rates of such than the control group.

The authors believe this study shows that bevacizumab holds promise in the treatment for ovarian cancer. They wrote, “The use of bevacizumab during and up to 10 months after carboplatin and paclitaxel chemotherapy prolongs the median progression-free survival by about 4 months in patients with advanced epithelial ovarian cancer.”

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Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484-96.
Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473-83.

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