RESEARCHERS ADVANCE TREATMENT, UNDERSTANDING OF OVARIAN CANCER
By Kristine M. Conner
Ovarian cancer kills nearly 15,000 women in the United States each year. Fewer than half of those diagnosed with the disease survive five years. Those grim statistics reflect, in part, the lack of a reliable means to detect ovarian cancer early: More than 80 percent of patients are diagnosed after the disease has traveled beyond the ovary. Finding better treatments is essential to improving survival, as is unlocking clues to the disease’s development. Studies by Fox Chase researchers released this spring made major contributions on both fronts.
A new strategy
Robert A. Burger, director of the Women’s Cancer Center, led an international Phase III clinical trial that found that adding bevacizumab (known by the trade name Avastin) to standard frontline chemotherapy for advanced ovarian cancer, then continuing treatment with it alone, extends patients’ progression-free survival—the time before the disease returns or worsens. Women receiving chemotherapy alone had a median progression-free survival time of 10.3 months, but those receiving bevacizumab, 14.1 months.
Frontline therapy: The medical therapy recommended for the initial treatment of a disease.
Clinical trial: Study of a drug, diagnostic, or other tool in humans. Clinical trials have four phases. Phase I assesses the product’s safety; subsequent phases assess efficacy.
Biomarker: A biological substance—often a protein— whose concentration reflects the presence or severity of a disease.
“This finding represents a 28-percent reduction in the risk of disease progression over time,” Burger notes. “This is a fairly high-risk population, so a four-month improvement is significant.” Bevacizumab interferes with angiogenesis, the process by which new blood vessels form to supply a tumor’s growth. Although the drug has been found to extend progressionfree survival for other cancers, this is the first Phase III trial showing it to be effective against advanced ovarian cancer.
Researchers will continue to analyze quality of life and overall survival among the study’s nearly 1,900 participants. In the meantime, Burger says, women diagnosed with advanced ovarian cancer have another frontline treatment strategy to discuss with their doctors. He hopes the study’s results will be confirmed by another Phase III trial under way in Europe, which might hasten FDA approval of the treatment regimen. “We believe this drug can be valuable in the treatment of this disease,” he says.
Where it all begins
Another key to improving ovarian cancer treatment will be finding ways to diagnose it at an earlier stage. In a separate study, researcher Jeff Boyd, chief of the division of molecular pathology, and colleagues from Memorial Sloan-Kettering Cancer Center produced groundbreaking evidence of how and where ovarian cancer originates.
“Unless you understand where cancer begins—what the precursor lesions might be—it is hard to develop an early detection or screening test,” Boyd says. “We have known precursor lesions in other cancers, such as cervical, colorectal, and breast. None of that knowledge has existed for ovarian cancer.”
Over six years, the researchers used a combination of microscopic and molecular imaging to examine ovarian tissue from three groups: women with mutations in BRCA tumor-suppressor genes, who have up to a 40-percent lifetime risk of ovarian cancer; those with no known genetic risk factors; and others with early-stage ovarian cancers. They found that most ovarian cancers develop inside cysts that form in the epithelium, the tissue that lines the ovary’s surface, and were able to identify early genetic events in the cells’ transformation.
All evidence pointed to inclusion cysts, which fold into the ovary from its surface, as the site of origin, and to dysplasia— early structural changes—and aneuploidy—having too many chromosomes—as key factors in the cell, Boyd says. “We could actually see the progression from completely normal epithelium through dysplasia to cancer,” he says.
The findings will be critical in the search for a reliable screening test, he says: “We’re at a place now where we can focus our efforts on looking for early lesions and early biomarkers, before cancer develops.”