New Clinical Study on the Relationship Between Imaging and OVA1®

A new study of OVA1® clinical performance, titled "The Effect of Ovarian Imaging on the Clinical Interpretation of a Multivariate Index Assay," has been released as an online advance publication of The American Journal of Obstetrics & Gynecology.

The study examines the relationship between two commonly used imaging methods - ultrasound (US) and computed tomography (CT) - and the OVA1 test result, in assessing the risk of ovarian cancer among patients planning surgery for an ovarian mass.

OVA1 is an FDA-cleared blood test that measures the levels of five proteins and then uses a proprietary algorithm and software called OvaCalc® to calculate a single risk score.

"This new study advances our understanding of how OVA1 and imaging work together in the pre-surgical assessment of ovarian cancer risk," said study co-author Fred Ueland, M.D., associate professor of gynecologic oncology at the University of Kentucky's Markey Cancer Center. "This is important for two reasons. First, adding OVA1 reduced the number of ovarian cancers missed with imaging alone, by 85 to 90 percent. Recent publications have reinforced that the first surgery is an important opportunity to improve ovarian cancer survival by ensuring that cancers are detected earlier and that they are operated on by the most experienced specialists. Second, this study provides new evidence of how menopausal status, imaging and OVA1 score may interrelate."

Dr. Scott Goodrich of the University of Kentucky led the study in collaboration with colleagues Drs. Fred Ueland and Rachel Ware Miller. The findings are the third in a series of subset analyses of data obtained from 1,100 ovarian mass surgery patients in two previous pivotal trials of OVA1 clinical performance, conducted in 2007 and 2012.

The authors compared the performance of each imaging method alone, to the performance of OVA1 alone (for risk stratification), as well as in combination with OVA1. In addition, the authors presented logistic regression models showing how menopausal status, high- or low-risk imaging and OVA1 score interact in the assessment of ovarian cancer risk.

The researchers concluded that "serum biomarkers and imaging are a complementary set of clinical tools and that when the [OVA1] score is further stratified by imaging risk and menopausal status, there is a better understanding of the clinical risk of ovarian malignancy."

This latest study brings the number of full research articles on OVA1 clinical performance to a total of five peer-reviewed publications. Together, these data provide strong, prospective clinical evidence that OVA1 improves the pre-surgical detection of ovarian cancer, regardless of stage or subtype, in patients undergoing surgery for a suspicious ovarian mass.

"The sensitivity of OVA1 is critical to the detection of ovarian malignancy, pre-surgical risk assessment and determining whether a woman may benefit from consultation with a gynecologic oncologist prior to surgery," said Donald Munroe, chief scientific officer and SVP of business development at Vermillion. "Vermillion is committed to fully developing this clinical evidence, together with future studies on how OVA1 may impact the efficiency and quality of care for women facing ovarian cancer, the deadliest of all gynecologic malignancies."

More than 22,000 women are diagnosed with ovarian cancer in the United States annually, and more than 12,000 die each year. Leading medical associations, including the American College of Obstetrics and Gynecology (ACOG), recommend that women with suspected ovarian cancer be referred to a gynecologic oncologist for surgery for the best potential outcomes. However, only an estimated one-third of women who have a malignant tumor are operated on by a gynecologic oncologist for the initial removal of cancer.

This publication, "The Effect of Ovarian Imaging on the Clinical Interpretation of a Multivariate Index Assay," is also co-authored by Dr. Robert Bristow (UC Irvine, Calif.), Dr. Joseph Santoso (The West Clinic, Tenn.), Dr. Zhen Zhang (Johns Hopkins Medical Institute) and Alan Smith (Applied Clinical Intelligence). It will be published in print in the 2nd quarter of 2014 in the American Journal of Obstetrics & Gynecology.

METHODS AND FINDINGS

The study evaluated a combined population from the OVA1 FDA registration and OVA500 confirmatory trials, for a total of 1,024 evaluable patients 18 years or older, and planning surgery for ovarian masses. To assess the value of OVA1 added to routine assessment, enrolling physicians were allowed to use their preferred method of imaging.

Since OVA1 is not indicated for women with clinical evidence of advanced ovarian cancer, ascites and metastatic implants, the small number of patients with these indicators was excluded from the analysis, leaving a total of 721 evaluable subjects who were imaged with ultrasound (US), and 313 with CT scanning.

Patients imaged with MRI were also excluded from the analysis due to low numbers (N=43) confounding statistical interpretation. Overall clinical performance of US, CT and OVA1 is presented in the Data Summary table below, along with the performance when OVA1 is combined with imaging as a logical "OR" function (along with the performance of OVA1 in combination with imaging as a logical "OR" function), per the product's risk stratification protocol.

In addition, this combination of ultrasound and OVA1 detected 95 percent of early-stage ovarian cancers, consistent with previous reports of the combined study population.