MADISON, Wis.—Exact Sciences Corp., the company behind the popular non-invasive colorectal cancer screening test Cologuard, has focused on a similar approach to identify a new mechanism to test for the most common type of liver cancer: hepatocellular carcinoma (HCC). Cologuard successfully utilizes methylated DNA biomarkers (MDMs), leading the scientists to explore whether the same class of biomarkers could be detected in blood and represent an important advancement in liquid biopsy for detecting HCC.
They documented extremely promising results by examining 443 patients, including 135 HCC cases and 308 age-matched and liver disease etiology-matched controls. The test demonstrated 80-percent sensitivity at 90-percent specificity with a novel combination of six blood-based biomarkers for HCC. The study also showed 71-percent sensitivity for early-stage HCC at 90-percent specificity. These results were compared to the current standard test of the alpha-fetoprotein (AFP) test, which demonstrated 45-percent sensitivity at 90-percent specificity for early-stage HCC. The findings were recently presented at the 2019 annual meeting for the American Association for the Study of Liver Diseases (AASLD) in Boston.
“When cancer is in its earliest stages in asymptomatic individuals, it can be the most difficult to detect through biomarker screening because of the natural history of early tumor development and cancer biology; targeted biomarkers may only be present in peripheral blood in very small amounts,” explained Scott Johnson, senior vice president of research and development at Exact Sciences. “Detecting individual or groups of biomarkers in very small concentrations challenges fundamental requirements for balancing the sensitivity and specificity of individual or panels of biomarkers. We have made progress with these challenges through improved methods of stabilization and purification of cell-free DNA from blood, as well by developing optimized, highly sensitive methods for interrogating methylated DNA. With specificity set at 90 percent, our novel combination of six blood-based biomarkers (four MDMs and two proteins) for HCC detection demonstrated 80-percent overall sensitivity, with 71-percent sensitivity for early-stage cancer (Barcelona Clinic Liver Cancer stages 0 and A).”
The test has been recognized as a Breakthrough Device by the U.S. Food and Drug Administration, and correspondingly is included in the Exact Sciences Breakthrough Devices program, which expedites development, assessment and review processes to provide patients and healthcare providers with timely access to new technologies.
The team is continuing to work diligently to finalize the development of their full combination of six blood-based biomarkers for HCC detection. They’ve presented three sets of data thus far, and plan to present additional data in 2020. The need is urgent—liver cancer is the fastest-growing cancer for both men and women in the United States, according to the American Cancer Society.
Says Johnson: “We are working to continue validating our HCC biomarkers and algorithm to provide an effective tool for helping detect HCC earlier in patients who are at risk of developing the disease. We plan to make this tool available in the second half of 2020 and expect to generate real-world evidence to support guideline inclusion, broad reimbursement and adoption of the test over time.”
Current guidelines encourage at-risk patients to submit to ultrasound testing, with or without the AFP blood test twice per year. While one’s three-year survival rate nearly doubles for those who undergo regular testing compared to those who do not, fewer than one-third of patients adhere to current guidelines.
“A growing number of patients around the world are considered high risk for developing HCC,” noted Kevin Conroy, chairman and CEO of Exact Sciences. “A more sensitive and convenient blood-based test could help catch the disease earlier, which may lead to better outcomes. We are encouraged by the data presented [at AASLD], as it shows an important advancement over the options currently available.”
These results are particularly compelling because Exact Sciences researchers are confident that methylated DNA biomarkers can be used to create similar sets of markers for several types of cancers. Their initial focus is on the deadliest cancers, and on creating tools based in advanced science and rigorous validation.
“We are looking at interventions across the cancer continuum and across many cancers to help patients and providers take life-changing action, earlier. We have successfully performed validation studies on tissue samples for thirteen cancers and on blood or other fluid samples for nine cancers,” Johnson stated. “Our team is highly motivated by the potential to make an impact on the lives of millions of patients diagnosed with these cancers each year by developing innovative tools rooted in rigorous science.”