An automated breast ultrasound system is on track to become the first such device with an indication for use as an adjunct to mammography when screening asymptomatic women with dense breasts for breast cancer.
The Food and Drug Administration’s Radiological Devices Panel voted 13-0 that the benefits of U-Systems Inc.’s somo-v automated breast ultrasound system outweigh the risks for breast cancer screening.
During their meeting, the advisory group also voted unanimously that the noninvasive device is safe and effective, despite FDA concerns over whether the firm’s pivotal study data could be generalized to a broader population.
Approval is not guaranteed, but the agency usually follows the advice of its advisory panels.
U-Systems is seeking premarket approval to increase breast cancer detection in asymptomatic women with dense breasts who have not had a previous clinical breast intervention following a negative mammogram screening. Somo-v was 510(k) cleared in 2005 for diagnostic use as an adjunct to x-ray mammography.
A key question the FDA asked the panel was whether the proposed expanded indication – and the way it would be applied in practice – was appropriately reflected in the firm’s pivotal study design. The panel agreed that it was.
The proposed indication for use "is fine the way it’s written," said panel member Dr. Carl D’Orsi, professor of radiology and hematology/oncology at Emory University in Atlanta. "It should not be changed," Dr. D’Orsi said, reflecting the panel’s consensus.
Premarket approval would make somo-v the first ultrasound device available in the United States with a breast cancer screening indication, according to the company. The system is already the only ultrasound device approved for breast cancer screening in Canada and Europe.
Supporting the premarket approval application is a retrospective, multireader study that enrolled 200 subjects at 13 U.S. sites – culled from the firm’s larger SOMO-INSIGHT clinical trial – to evaluate whether digital mammography in combination with the somo-v automated breast ultrasound system (ABUS) is more sensitive in detecting breast cancer in women with dense breast tissue than x-ray mammography screening alone.
The primary end point of the study was to determine radiologist readers’ performance with and without ABUS using a statistical methodology called "receiver operator characteristic" curve analysis. The mean area under the curve (AUC) values were 0.604 for x-ray mammography alone and 0.747 for x-ray mammography plus ABUS.
"Results from our pivotal clinical retrospective reader study demonstrate that use of screening mammography with ABUS provides a substantial, statistically significant clinical improvement in a reader’s ability to detect mammographically negative breast cancers," said CEO Ronald Ho during the meeting.
"Our primary end point was met," added principal investigator Maryellen Giger, Ph.D., professor of radiology at the University of Chicago.
The difference of 0.143 in the AUC values "was statistically significant, given that the lower bound of an estimated 95% confidence interval for the difference in AUC is 0.074," the FDA agreed.
According to the company, mammography’s sensitivity for the detection of breast cancer is 85% in women overall, but the rate is reduced to 65% in women with dense breast tissue. "Dense breast tissue has been proven to conceal malignant lesions, limiting the effectiveness of mammography," Mr. Ho said. Dense breast tissue also increases a woman’s risk of breast cancer by up to four to six times, according to U-Systems.
"What differentiates our device is that we can detect lesions that are missed by mammography ... and we do it in a very fast work flow that’s reproducible and operator independent," the firm stated. The technology is designed to follow the same work flow as a traditional mammography procedure and provide an exam in 15 minutes.
Real-World Management Questioned
The FDA questioned whether the pivotal study’s results could be extrapolated to a real-world population of patients. One hundred sixty-four subjects were used in the study’s primary statistical analysis (133 normal cases chosen at random and 31 cancer cases), with 12 noncancer cases being evaluated by mammography alone.
Patients with prior clinical breast interventions, such as those who had a breast augmentation or breast cancer treatments including biopsy, radiation, lumpectomy, or mastectomy, were excluded from the study. U-Systems said it excluded these patients to eliminate potential bias and/or confounding effects.
But while the firm is seeking approval of somo-v as a screening tool for women with dense breasts "who have not had a previous clinical breast intervention," the FDA argued that in the real world, "patient management that includes an ABUS scan may be considered for patients who have had prior clinical breast intervention."