FDA Approves Exact Sciences’ Cologuard Plus Test for Colorectal Cancer Screening

The US Food and Drug Administration has approved Exact Sciences’ Cologuard Plus test, the company’s next-generation multitarget stool DNA test, for adults ≥ 45 years of age at average risk for colorectal cancer (CRC).

The approval was based on findings from the BLUE-C study, one of the largest prospective, head-to-head studies ever conducted in CRC screening. Among a subset of nearly 19,000 average-risk participants, the Cologuard Plus test demonstrated 95% overall cancer sensitivity and 43% sensitivity for advanced precancerous lesions at 94% specificity with no findings on colonoscopy.

Additionally, findings from BLUE-C also showed the Cologuard Plus test significantly outperformed an independent fecal immunochemical test (FIT), the OC-AUTO FIT from Polymedco, for overall CRC sensitivity, treatable-stage CRC sensitivity, high-grade dysplasia sensitivity, and advanced precancerous lesion sensitivity.

“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 Imperiale, MD, a 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 press release. “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.”

A multi-center, prospective study of more than 20,000 adults ≥ 40 years of age, BLUE-C was designed to evaluate the performance of the Cologuard Plus test (multi-target stool DNA or mt-sDNA) and Exact Sciences’ blood-based colorectal cancer screening test. Using colonoscopy as a reference method, the study directly compared the Cologuard Plus test and an independent FIT

The primary outcomes of interest for the study were the sensitivity for colorectal cancer and specificity for advanced neoplasia of the next-generation multitarget stool DNA test, with sensitivity defined as the proportion of participants with colorectal cancer who have positive test results and specificity defined as the proportion of negative test results among participants without advanced neoplasia.

Results showed colorectal cancer was present among 0.5% (n = 98) of participants. Of these, 84% (n = 82) had stage I, II, or III disease. Further analysis indicated 10.6% (n = 2144) had advanced precancerous lesions, 6973 (n = 34.6%) had nonadvanced adenomas, and 10,961 (n = 37.2%) had nonneoplastic findings or negative colonoscopy.

Results suggested the next-generation multitarget stool DNA test identified 92 of 98 participants with colorectal cancer and 76 of 82 participants with screening-relevant cancers, which yielded test sensitivities of 93.9% (95% confidence interval [CI], 87.1 to 97.7) and 92.7% (95% CI, 84.8 to 97.3), respectively. Investigators highlighted additional analyses of the next-generation multitarget stool DNA test revealed a sensitivity of 43.4% (95% CI, 41.3 to 45.6) for advanced precancerous lesions and specificity of 92.7% (95% CI, 92.2 to 93.1) for nonneoplastic findings or negative colonoscopy.

In comparison, the commercially available FIT had a recorded sensitivity of 67.3% (95% CI, 57.1 to 76.5) for colorectal cancer and 23.3% (95% CI, 21.5 to 25.2) for advanced precancerous lesions, but a specificity of 94.8% (95% CI, 94.4 to 95.1) for advanced neoplasia and 95.7% (95% CI, 95.3 to 96.1) for nonneoplastic findings or negative colonoscopy.

According to a press release from Exact Sciences, the company expects to launch the Cologuard Plus test with Medicare coverage and guideline inclusion in 2025 with support from Exact Sciences’ ExactNexus technology platform.

“Cologuard Plus sets a new performance standard in non-invasive colorectal cancer screening for patients,” Kevin Conroy, chairman and CEO of Exact Sciences, said. “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. ^{Exact Sciences. FDA Approves Exact Sciences’ Cologuard Plus™ Test, Setting A New Benchmark in Non-Invasive Colorectal Cancer Screening. October 4, 2024. Accessed October 4, 2024. https://www.exactsciences.com/newsroom/press-releases/fda-approves-exact-sciences-cologuard-plus-test}
2. ^{Campbell, P. Next-Gen Cologuard Test Shows Promise for Early Detection of Colorectal Cancer. HCPLive. March 13, 2024. Accessed October 4, 2024. https://www.hcplive.com/view/next-gen-cologuard-test-shows-promise-for-early-detection-of-colorectal-cancer}