Published in UAB Insight, Spring 2008
Bevacizumab for Ovarian Cancer
Overexpression of proangiogenic factors plays a central role in the development of human malignancies, and particularly in cancer of the ovary. Preclinical and human studies show that one such factor — vascular endothelial growth factor (VEGF) — is an important mediator of tumor initiation and growth.
“VEGF overexpression in ovarian cancer is linked to formation of ascites, early disease recurrence, and poor prognoses,” says UAB Division of Gynecological Oncology Director Ronald D. Alvarez, MD, whose group is investigating bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody, for therapy of ovarian and other gynecologic cancers. UAB has been a leader in the development and study of molecularly targeted therapeutics such as bevacizumab and has previously tested the agent in patients with breast and colorectal cancer.
“Avastin is designed to bind to VEGF and block its stimulation of angiogenesis and new tumor growth,” he says. “Another important mechanism of action may be its ability to decrease intratumoral pressures so that chemotherapy is better able to permeate malignant tissue.”
Active Agent
UAB is testing bevacizumab as both a single agent and in combination with traditional platinum-based and other chemotherapeutic regimens. The results of early clinical trials, Alvarez says, suggest bevacizumab is the most active antiangiogenic agent developed so far.
Previous studies of the drug in ovarian cancer have focused mainly on its efficacy in patients with relapsed and platinum–resistant disease. The Journal of Clinical Oncology recently published results of two key phase 2 trials of bevacizumab as a single agent in relapsed ovarian cancer. In the study by Burger et al (2007;33:5165-5171) participants had undergone one or two prior chemotherapy regimens. A second study by Cannistra et al (2007;33:5180-5186) enrolled platinum-resistant patients who had received as many as three previous chemotherapy regimens. Objective response rates were 21% and 16%, respectively, and 52% and 64% of patients achieved stable disease with median progression-free survival of 4.4 and 4.5 months.
Promising results are motivating investigators to test bevacizumab as a first-line agent. UAB is participating in the phase 3 Gynecological Oncology Group study 218 (GOG-218), which is enrolling patients with newly diagnosed advanced-stage ovarian cancer. GOG-218 is comparing carboplatin plus paclitaxel, the standard of care for surgically debulked patients, with the same regimen plus bevacizumab. “This exciting trial will test bevacizumab in combination with primary chemotherapy and will study its effectiveness as maintenance therapy,” Alvarez says. A second phase 3 trial is randomizing platinum-sensitive patients with recurrent ovarian cancer to paclitaxel and carboplatin or the same regimen plus bevacizumab.
Alvarez says patients have tolerated bevacizumab well, and bowel perforation, the major complication seen in previous trials, has affected only a few individuals in UAB investigations. “Careful patient selection is important,” he says. “Patients who are heavily pretreated seem more likely to develop this problem. Bevacizumab is an important addition to our arsenal of drugs for ovarian cancer. I have been impressed by its activity and effect on quality of life of our patients.”
For more information:
Dr. Ronald Alvarez
1.800.UAB.MIST
mist@uabmc.edu