FDA Approves Cologuard Plus, Next-Gen Noninvasive Colorectal Cancer Screening Test

The US FDA today approved Cologuard Plus, a multitarget next-generation stool DNA test, for adults at least 45 years of age who are at average risk for colorectal cancer (CRC), according to a news release from Exact Sciences.¹

The company anticipates launching Cologuard Plus with Medicare coverage and guideline inclusion in 2025, the statement said.

The agency’s decision was based on findings from the pivotal multicenter prospective BLUE-C study in which, among a subset of 20 176 evaluable adults undergoing screening colonoscopy, Cologuard Plus showed an overall sensitivity for CRC of 93.9%, a specificity for advanced neoplasia of 90.6% as well as 43.4% sensitivity for advanced precancerous lesions at 92.7% specificity for nonneoplastic findings or negative colonoscopy.¹

The findings from BLUE-C, 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 Cologuard Plus 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

“To meaningfully improve outcomes in colorectal cancer, 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, 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 the press statement.¹ “The high colorectal cancer 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.”¹

“To meaningfully improve outcomes in colorectal cancer, we must catch cancer early – when it is most treatable – and find advanced precancers, which can prevent cases of this cancer.”

The test’s increased specificity over the original iteration of Cologuard will reduce the potential need for follow-up colonoscopy, according to the statement.¹ The 91% specificity reported in the BLUE-C trial for patients with advanced neoplasia improves on the 87% specificity reported in the original FDA registrational trial for Cologuard.³ For individuals whose colonoscopy findings were negative or nonneoplastic, the next generation Cologuard test reached a specificity of 93%. In this category, the specificity for FIT was 96%.³

BLUE-C evaluated 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.¹ Approximately 40% of the participants self-identified as Hispanic or Latino, Black, Asian, American Indian, or Alaska Native, or Pacific Islander. The representative, multiethnic study population increases the likelihood that the BLUE-C findings and the Cologuard Plus test itself are relevant for all screen-eligible individuals, regardless of race or ethnicity.¹

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

The next-generation test was developed in collaboration with the Mayo Clinic and uses a novel set of biomarkers in addition to improved laboratory processed. Enhanced sample stability features will extend the time individuals have to return samples and “increase the valid result rate,” according to Exact Sciences.

“Cologuard Plus sets a new performance standard in noninvasive [CRC] screening for patients” detecting “cancers and precancerous polyps with even greater sensitivity than Cologuard while reducing false positives by more than 30%. This breakthrough comes at a critical time, when 60 million Americans are not up to date with screening,” Kevin Conroy, chairman and chief executive officer at Exact Sciences, concluded.¹

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
   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