Next-Generation Cologuard Improves Colorectal Cancer Detection, False Positive Rates in BLUE-C

A next-generation, multitarget stool DNA test—that which combines a trio of novel methylated DNA markers and fecal hemoglobin for the screening of average-risk colorectal cancer (CRC)—provided improved sensitivity scores for the detection of any CRC versus standard fecal immunochemcial test (FIT), according to new data.¹

New late-breaking abstract research presented at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, BC this weekend showed the Exact Sciences Corp’s next-generation Cologaurd test met all endpoints in the pivotal BLUE-C trial, including a demonstrated 94% sensitivity for CRC at 91% specificity.

Presented by study investigator Thomas F. Imperiale, MD, professor of medicine at Indiana University Medical Center, the new BLUE-C data additionally showed the next-generation Cologaurd test was significantly more likely detect both cancer (93.9% vs 67.3%) and advanced precancerous lesions (APLs; 43.4% vs 23.3%) than FIT. The multitarget stool DNA test additionally showed a greater sensitivity for the detection of APL high-grade dysplasias than FIT (75% vs 47%; P <.0001).

The findings from the 26,000-plus participant trial that spanned late 2019 to early 2023 provides validation for the utility and accuracy of the latest iteration of Cologaurd, with Paul Limburg, MD, MPH, chief medical officer of Screening for Exact Sciences calling it “a new standard in non-invasive colorectal cancer and precancer detection.”²

In an interview with HCPLive during ACG 2023, Imperiale highlighted a number of the topline findings from BLUE-C—beginning with the improvement in specificity relative to the prior generation of Cologuard. He called the reduction in false positives with the next-generation screening tool the most important takeaway from the pivotal trial.

“And (Exact Sciences) did that without losing sensitivity—because normally, if you increase one (parameter of the test), the other goes down,” Imperiale said. “But because this has new markers in it, it still has fetal hemoglobin, but the markers are different, the performance of the test is different.”

Imperiale envisions the next-generation Cologaurd will be most viable for screening patients not at higher risk for CRC—persons who may not opt for an initial colonoscopy screening nor an annual FIT test. Theoretically, these individuals may be seeking a 3-year reprieve from necessary CRC screenings.

“That could conceivably be the people in the 45 - 49 year old range—it's a group where guidelines a few years ago reduced the age (to include them for screening),” Imperiale said. “They're relatively new to the cancer screening landscape, and they may be the population who's best suited for this. And the specificity performed particularly well in that group, it was equivalent to FIT.”

References

1. ^{Imperiale TF, Porter K, Zella J, Gangart ZD, et al. 54 - Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening: A Prospective Clinical Validation Study (BLUE-C) (Late-Breaking Abstract). Paper presented at: ACG 2023 Annual Scientific Meeting. Vancouver, BC, Canada. October 20 – 25, 2023.}
2. ^{Exact Sciences. NEXT-GENERATION COLOGUARD® TEST DEMONSTRATES HIGH SENSITIVITY AND SPECIFICITY IN PIVOTAL BLUE-C STUDY, SIGNIFICANTLY OUTPERFORMING FECAL IMMUNOCHEMICAL TESTING (FIT) FOR CANCER AND PRECANCER DETECTION. Press release. Published October 22, 2023. https://www.exactsciences.com/newsroom/press-releases/next-generation-cologuard-test-demonstrates-high-sensitivity-and-specificity-in-pivotal-blue-c-study}