Next-Generation Cologuard Surpasses FIT for Colorectal Cancer Detection in Pivotal BLUE-C Trial

_{^{©Sebastian Kaulitzky/stoc.adobe.com}}

The multitarget next-generation stool DNA test Cologuard Plus demonstrated sensitivity of 94% for colorectal cancer (CRC) at a specificity of 91% for advanced neoplasia in a cohort of 20 000 adults aged 40 years and older at average risk who were undergoing routine screening colonoscopy.¹

The findings, from the BLUE-C study, were published in the New England Journal of Medicine² on March 14, also showed that in the first head-to-head comparison with fecal immunochemical testing (FIT) the next-gen Cologuard was significantly more likely to detect CRC (94% vs 67%; P < .001) or advanced precancerous lesions (APL; 43% vs 23%; P < .001).² The advanced test also showed higher sensitivity than FIT for high-grade neoplasia, the most clinically significant form of advanced precancerous lesions at 75% vs 47% ( P < .001)²

Importantly, the performance of the next-gen DNA test was even better in younger age groups, at a specificity of 96% in individuals aged 45-54 years, a population at increasingly high risk for CRC.¹

“Cologuard Plus is highly sensitive for detecting colorectal cancer,” Thomas F Imperiale, MD, professor of medicine at the Indiana University School of Medicine, research scientist at the Regenstrief Institute, and principal investigator for the BLUE-C study said in a statement from Cologuard Plus developer Exact Sciences.¹ “This noninvasive test also detected a good proportion of the most advanced precancerous lesions and did so with a low number of false-positive test results.”¹

The test’s increased specificity over the previous iteration of Cologuard will reduce the potential need for follow-up colonoscopy, according to the statement. The 91% specificity reported in the BLUE-C trial for patients with advanced neoplasia improves on the 87% specificity reported in Deep-C, the FDA registrational trial for Cologuard.³ For individuals whose colonoscopy findings were negative or non-neoplastic, the next generation Cologuard test reached a specificity of 93%. In this category, the specificity for FIT was 96%.³

BLUE-C was a prospective, multicenter study enrolling 20 176 individuals, evaluating the sensitivity of the multitarget stool DNA Cologuard Plus. The cohort was created based on the 2020 US census and aligns with the racial and ethnic diversity of the US, according to Exact Sciences.³ In an effort to expand the eligible screening population beyond those at average risk for CRC, a small subset (1000) of participants was enrolled that had a first-degree relative with a history of CRC. Among the study’s findings, the sensitivities for CRC and APLs were similar among participants with or without a family history.¹

Researchers used colonoscopy as a reference method in their direct comparisons of Cologuard Plus and an independent FIT.

“BLUE-C’s publication in the New England Journal of Medicine reflects a decade of deep scientific and medical research in collaboration with Mayo Clinic,” Kevin Conroy, chairman and CEO of Exact Sciences, said in the company statement.¹ “We’re eager to bring an improved, noninvasive colorectal cancer screening test to patients in Cologuard Plus, as colorectal cancer remains the most preventable, yet least prevented cancer.”¹

Exact Sciences submitted its pre-market approval (PMA) application for Cologuard Plus to the US Food and Drug Administration (FDA) in December 2023, including complete results from BLUE-C. Pending FDA approval, the company plans to make the test available in 2025.¹

References

1. The New England Journal of Medicine publishes Cologuard Plus test results from pivotal BLUE_C study. News release. Exact Sciences. march 13, 2024. Accessed March 21, 2024. https://www.exactsciences.com/newsroom/press-releases/new-england-journal-of-medicine-publishes-cologuard-plus-test-results-from-pivotal-blue-c-study

2. Imperiale TF, Porter K, Zella J, et al, for the BLUE-C study investigators. Next-generation multitarget stool DNA test for colorectal cancer screening. New Engl J Med. 2024;390:984-993. doi:10.1056/NEJMoa2310336

3. 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. News Release. Exact Sciences. October 22, 2023. Accessed March 21, 2024. https://www.exactsciences.com/newsroom/press-releases/next-generation-cologuard-test-demonstrates-high-sensitivity-and-specificity-in-pivotal-blue-c-stud