Twice the power for two-gene test

Clinical Genomics’ ctDNA blood test outperforms CEA in detecting colorectal cancer recurrence

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BRIDGEWATER, N.J.—According to the American Cancer Society, colorectal cancer is presently the third most common cancer diagnosed in both men and women, excluding skin cancers. It is “the third leading cause of cancer-related deaths in the United States when men and women are considered separately, and the second leading cause when both sexes are combined,” the organization notes, and was expected to account for some 49,000 deaths in 2016. Many of those deaths are due to the high recurrence rate, and Clinical Genomics, which focuses on diagnostic products for colorectal cancer, is hoping to help with a new detection tool.
The company is advancing a two-gene circulating tumor DNA (ctDNA) blood test to monitor colorectal cancer (CRC) patients after surgery. The test measures the presence of BCAT1 and IKZF1 gene methylation, a chemical modification associated with tumor growth and invasion. In recent work, Clinical Genomics’ test has been found to detect twice the number of recurrence cases as carcinoembryonic antigen (CEA) testing, which is a standard-of-care component for CRC recurrence monitoring in patients who have been through surgery.
The company recently announced that data supporting the test in recurrence monitoring was published online in Cancer Medicine and appeared in the October 2016 issue.
“Given that at least 30 percent of patients in remission from CRC following initial treatment will develop recurrence, improved surveillance methods that accurately detect recurrence are essential for improving outcomes for patients,” said contributing study author Dr. Graeme P Young, Matthew Flinders Distinguished Professor at Flinders University Centre for Innovation in Cancer. “Data from this study reinforce previous findings that ctDNA can be reliably detected in CRC patients. Furthermore, the results suggest that when used in ongoing surveillance of cases in remission, a positive BCAT1/IKZF1 test has the potential to establish a new approach for earlier detection of recurrent CRC by detecting more unsuspected recurrences and triggering earlier imaging studies. Additional prospective studies of the methylated BCAT1/IKZF1 test compared with CEA are ongoing.”
In a study comparing the sensitivity and specificity of Clinical Genomics’ two-gene blood test with CEA in detecting recurrence following remission, 357 participants were recruited, with recurrence status established for 220 subjects. Of those, 122 had blood samples available for analysis. Within those 122 subjects, 28 presented with recurrence while 94 had no clinically detectable disease. In the population with recurrent cancer, 67.9 percent (19 out of 28) tested positive for methylated BCAT1/IKZF1 (i.e. the marker was detectable), while only 32.1 percent (9 out of 28) tested positive for CEA. Among the patients with no clinically detectable disease, there was no significant difference in the percentage positive for methylated BCAT1/IKZF1 compared to CEA.
Sensitivity estimates of the methylated BCAT1/IKZF1 test within the test population were 75 percent and 66.7 percent for local and distant recurrence, respectively, compared with 50 percent and 29.2 percent for CEA. Nine patients registered as positive for both tests, while Clinical Genomics’ test detected another 10 cases that CEA failed to identify.
Dr. Lawrence LaPointe, president and CEO of Clinical Genomics, tells DDNews that recurrence is particularly high in colorectal patients. Of patients who receive treatment for colorectal cancer, he says, between 30 and 50 percent will have a relapse, and of those, some 80 percent of recurrences take place within two years.
“An inability to detect early molecular changes consistent with underlying tumorigenesis can result in recurrent colorectal cancer going undetected or being discovered in the later stages of disease when clinical intervention is less likely to be effective,” said LaPointe. “These data demonstrate that a blood-based ctDNA test for methylated BCAT1/IKZF1 routinely detects recurrence that CEA testing misses. We believe our two-gene test has the potential to fill an urgent and unmet clinical need, and are committed to advancing its clinical development as a new tool for improving patient outcomes.”
“There’s a broad level of introduction of genomic-based testing entering the market over the last year or two, and probably will continue to accelerate,” he adds. “In that space, there’s a much better understanding of gene mutations, how they may affect certain chemical pathways for chemotherapy. There’s lots of work going on in terms of understanding different genomic profiling and how that might better understand a person’s disease as aggressive, non-aggressive, so in the broad sense, there’s been a lot of growth.
“Genomics has been a really hot field, and in particular there’s a buzz around liquid biopsies, looking for genomic-based biomarkers in circulation, as opposed to starting everything from a tissue sample or a tumor specimen.”

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