American College of Gastroenterology (ACG) gives BLUE-C study late breaker status at 2023 annual meeting with presentation of the only head-to-head study results versus FIT at ACG

High specificity for next-generation Cologuard test expected to minimize unnecessary follow-up colonoscopies, supporting positive patient experiences¹

Additionally, results show the next-generation Cologuard test was significantly more likely to detect cancer or precancer than fecal immunochemical testing (FIT)* (94% vs 67% and 43% vs 23%, respectively).^[1]  Finally, the next-generation Cologuard test demonstrated higher sensitivity for the most clinically significant form of advanced precancerous lesions (high-grade dysplasia at 75%) than FIT (47%).^[1]    

BLUE-C is one of the largest, most robust CRC screening trials ever conducted. It included more than 20,000 evaluable subjects in a population that aligns to the racial and ethnic diversity of the United States.^[1,2] Among these participants, the BLUE-C trial identified a total of 98 participants with colorectal cancer. Of these 82 (83.7%) had stage I to III cancers.^[1] 

"BLUE-C results demonstrate a new standard in non-invasive colorectal cancer and precancer detection, building on the strengths of current Cologuard," said Paul Limburg, MD, MPH, AGAF, chief medical officer, Screening, Exact Sciences. "The high sensitivity and specificity reported in BLUE-C will help drive improvement in patient experiences and will contribute to our quest to improve outcomes for this deadly cancer via accurate early detection."

Note: FIT positivity cut-off: hemoglobin >100 ng/mL. Colorectal cancer stages were defined per the American Joint Committee on Cancer Staging System, 8th ed.

BLUE-C Reports High Specificity

In addition to superiority over FIT in sensitivity for both colorectal cancer and advanced precancerous lesions, the next-generation Cologuard test demonstrated 91% specificity.¹ The specificity for FIT was 95%.^[1]

"Improving specificity of non-invasive stool-based screening tests while maintaining high sensitivity is a critical step in advancing the detection and prevention of colorectal cancer and minimizing the potential for unnecessary follow-up colonoscopies," said Thomas F. Imperiale, MD, Professor of Medicine at the Indiana University School of Medicine, research scientist at the Regenstrief Institute, and principal investigator for BLUE-C.

The 91% specificity reported in the BLUE-C trial for patients without advanced neoplasia is higher than the 87% specificity reported in Deep-C, the FDA registrational trial for Cologuard.^[1,3] For patients with a negative or non-neoplastic  findings on colonoscopy, specificity for the next-generation Cologuard test reached 93%. In this category, the specificity for FIT was 96%.^[1]  

Additional Analysis Presented at ACG Further Supports Performance of Next-Generation Cologuard

In addition to the BLUE-C pivotal data shared at ACG, Exact Sciences presented an analysis that describes a performance evaluation and validation of the next-generation Cologuard algorithm using a set of known test samples from the original Cologuard pivotal study (DeeP-C). In this additional analysis, all performance estimates of next-generation Cologuard performance were equivalent to or higher than the first-generation Cologuard test, confirming reproducibility and supporting clinically relevant performance of the next-generation Cologuard test.^[4]

"Promising data from the BLUE-C trial involving 20,000 patients is being presented at the American College of Gastroenterology," said Seth A. Gross, MD, professor of medicine, NYU Grossman School of Medicine. "The findings indicate that the next-generation mt-sDNA test demonstrates even higher sensitivity for colorectal cancer screening (94%) and high-grade dysplasia (75%), compared with the current Cologuard test.  These findings suggest that, if FDA approved, the mt-sDNA test will be a valuable option in providing non-invasive colorectal cancer screening."