FDA Approves Cologuard Plus for Adults at Average Risk for CRC

The FDA has approved the Cologuard Plus test, a next-generation multitarget stool DNA test, for adults at least 45 years of age who are at average risk for colorectal cancer (CRC).¹

This regulatory decision was supported by findings from the observational BLUE-C trial (NCT04144738), in which, among a subset of 20,176 evaluable adults undergoing screening colonoscopy, Cologuard Plus showed 93.9% (95% CI, 87.1%-97.7%) overall CRC sensitivity, a specificity for advanced neoplasia of 90.6% (95% CI, 90.1%-91.0%), as well as 43.4% (95% CI, 41.3%-45.6%) sensitivity for advanced precancerous lesions at 92.7% (95% CI, 92.2%-93.1%) specificity for nonneoplastic findings or negative colonoscopy.²

The trial also demonstrated that the sensitivity of Cologuard Plus significantly outperformed that of an independent fecal immunochemical test (FIT) for overall CRC (FIT, 67.3%; 95% CI, 57.1%-76.5%; P < .001), stages I to III CRC (Cologuard Plus, 92.7%; FIT, 64.6%), advanced precancerous lesions (FIT, 23.3%; 95% CI, 21.5%-25.2%; P < .001), proximal CRCs (Cologuard Plus, 88.2%; FIT, 58.8%), distal CRCs (Cologuard Plus, 96.9%; FIT, 71.9%), sessile serrated lesions (Cologuard Plus, 45.8%; FIT, 5.2%), and high-grade dysplasia (Cologuard Plus, 74.6% [95% CI, 65.6%-82.3%]; FIT, 47.4% [95% CI, 37.9%-56.9%]). However, the FIT outperformed Cologuard Plus regarding specificity for advanced neoplasia (FIT, 94.8% (95% CI, 94.4%-95.1%), nonneoplastic findings or negative colonoscopy 95.7% (95% CI, 95.3%-96.1%), and negative colonoscopy (Cologuard Plus, 93.4% [95% CI, 92.8%-93.9%]; FIT, 96.0% [95% CI, 95.5%-96.4%]).

“To meaningfully improve outcomes in CRC, we must catch cancer early – when it is most treatable – and find advanced precancers, which can prevent cases of this cancer,” Thomas F. Imperiale, MD, a professor of medicine at the Indiana University School of Medicine in Indianapolis, a research scientist at the Regenstrief Institute, and principal investigator for the BLUE-C study, stated in a news release.¹ “The high CRC sensitivity and specificity of the Cologuard Plus test gives me confidence in the test’s ability to do just that while simultaneously maintaining a low risk of false positives. This makes the Cologuard Plus test a strong option for first-line screening of average risk patients.”

The multicenter, prospective BLUE-C trial included individuals 40 years of age and older, with a mean age of 63.0 years. The population was diverse and deemed reflective of the US population; 39.9% of participants identified as Hispanic or Latino, Black, Asian, American Indian or Alaska Native, or Pacific Islander. The trial’s primary outcomes included the sensitivity of Cologuard Plus for CRC and the specificity of Cologuard Plus for advanced neoplasia, defined as CRC or advanced precancerous lesions. Secondary outcomes included sensitivity for advanced precancerous lesions and specificity for nonneoplastic findings or negative colonoscopy, as well as the comparison of sensitivities for CRC and advanced precancerous lesions between Cologuard Plus and a commercially available FIT.

CRC was detected in 98 participants, 92 of whom were identified by Cologuard Plus, and 82 of whom had stage I, II, or III disease. Additionally, 2144 participants had advanced precancerous lesions, 6973 participants were found to have nonadvanced adenomas, 3451 participants had nonneoplastic findings, and 7510 participants had negative colonoscopy results.

Cologuard Plus shows 91% specificity when including non-advanced findings, 93% specificity when including no findings, and 94% specificity when age-weighted to the United States population with no findings on colonoscopy, according to the news release.¹

Notably, investigators reported no adverse effects with the stool-collection process for Cologuard Plus or the FIT.²

“Cologuard Plus sets a new performance standard in noninvasive CRC screening for patients,” Kevin Conroy, Chairman and CEO of Exact Sciences, added in the news release.¹ “Cologuard Plus detects cancers and precancerous polyps with even greater sensitivity than Cologuard while reducing false positives by more than 30 percent. This breakthrough comes at a critical time, when 60 million Americans are not up to date with screening.”

References

1. FDA approves Exact Sciences’ Cologuard Plus test, setting a new benchmark in non-invasive colorectal cancer screening. News release. Exact Sciences. October 4, 2024. Accessed October 4, 2024. https://www.exactsciences.com/newsroom/press-releases/fda-approves-exact-sciences-cologuard-plus-test
2. Imperiale TF, Porter K, Zella J, et al. Next-generation multitarget stool DNA test for colorectal cancer screening. New Engl J Med. 2024;390(11):984-993. doi:10.1056/NEJMoa2310336