A Phase III Gynecologic Oncology Group (GOG) clinical trial finds that adding bevacizumab (Avastin?), a humanized anti-VEGF monoclonal antibody, to initial chemotherapy treatment ? and then giving bevacizumab as maintenance therapy ? significantly slows disease progression in women with advanced epithelial ovarian, primary peritoneal or fallopian tube cancer. The results of the study were presented during the 46th annual meeting of the American Society of Clinical Oncology being held from June 4 – 8 in Chicago, Illinois (USA).
?This is the first time a Phase III trial has demonstrated that an anti-angiogenic agent improved progression-free survival (PFS) in women with this very hard-to-treat disease,? said lead researcher Robert A. Burger, MD, director of the Women?s Cancer Center at Fox Chase Cancer Center in Philadelphia, and GOG Lead Investigator. ?Based on the results of this GOG trial, bevacizumab is an acceptable initial treatment option for patients with advanced ovarian, primary peritoneal and fallopian tube cancers.?
Ovarian cancer is the sixth most commonly diagnosed cancer in women and the eighth leading cause of cancer death among women worldwide. Annually, an estimated 230,000 women will be diagnosed with ovarian cancer around the world and approximately 140,000 will die from the disease. Currently, treatment options for women with this disease are limited to surgery, and chemotherapy. Ovarian cancer is associated with high concentrations of vascular endothelial growth factor (VEGF), a protein associated with tumor growth and spread. Studies have shown a correlation between a high concentration of VEGF and a poorer prognosis in women with ovarian cancer.
Bevacizumab, which blocks the development of tumor growth-promoting blood vessels, is approved for several metastatic cancers, including those of the colon, breast, kidney, brain and lung. Previous small clinical trials showed promising activity in patients with recurrent ovarian and peritoneal cancer.
This international, double-blind, placebo-controlled phase III trial, included 1,873 women with a media age of 60, with newly diagnosed stage III or IV ovarian, primary peritoneal or fallopian tube cancer who had undergone surgery to remove as much of the cancer as possible.
Patients were randomly assigned to one of three groups: standard chemotherapy (paclitaxel plus carboplatin) and placebo plus placebo maintenance; standard chemotherapy with bevacizumab plus placebo maintenance; or standard chemotherapy with bevacizumab, followed by bevacizumab maintenance. Maintenance therapy is defined as longer-term treatment given after standard chemotherapy, with the goal of extending cancer progression-free survival.
The researchers found that women who received standard chemotherapy plus bevacizumab followed by up to 10 months of bevacizumab maintenance had a longer period of progression-free survival (median of 14.1 months) compared with those who received standard chemotherapy alone (median of 10.3 months), a difference that was statistically significant. Those who received chemotherapy and bevacizumab followed by placebo maintenance had a median progression-free survival of 11.2 months, a difference that was not statistically significant compared with those who received standard chemotherapy alone.
Although patients experienced bevacizumab-associated side effects (primarily hypertension and low white blood cell counts), the types and frequency appeared to be similar to what has been reported previously.
Lead author: Robert A. Burger, MD, Fox Chase Cancer Center, Philadelphia, PA
Date: Sunday, June 6, 2010, 1:45-2:00 PM CDT
Location: N Hall B1
Abstract: LBA 1
Title: Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer or Fallopian tube cancer (FTC): A Gynecologic Oncology Group study.
Authors: R. A. Burger, M. F. Brady, M. A. Bookman, J. L. Walker, H. D. Homesley, J. Fowler, B. J. Monk, B. E. Greer, M. Boente, S. X. Liang.