Natera, Inc. presented new data at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium (ASCO GI) showcasing the utility of its Signatera test in colorectal cancer (CRC) management. The presentations highlighted Signatera's performance in minimal residual disease (MRD) detection, early cancer detection, and a novel tissue-free MRD assay.
Signatera's Impact on Colorectal Cancer Outcomes
The BESPOKE CRC study, a large prospective, observational, multicenter MRD study in the U.S., demonstrated Signatera's capability as both a prognostic and predictive biomarker. In over 1,000 CRC patients, post-surgical Signatera positivity was strongly predictive of inferior outcomes in both stage II (HR=10.4; p<0.0001) and stage III (HR=10.1; p<0.0001) patients. The 24-month disease-free survival (DFS) estimates for stages II-III combined were 91.7% for Signatera-negative patients and 41.4% for Signatera-positive patients.
Purvi K. Shah, MD, MBBS, from Virginia Cancer Institute, presented the final analysis of the BESPOKE CRC sub cohort, emphasizing the potential of Signatera-based MRD detection for treatment decision-making. The study also indicated that Signatera-positive patients benefited from adjuvant treatment, while Signatera-negative patients did not, and clearance of ctDNA during and after treatment led to superior DFS outcomes.
Clinical Utility in Treatment Decisions
Additional data from the BESPOKE CRC study illustrated the impact of MRD detection on clinical decision-making. A significant number of oncologists reportedly escalated or de-escalated post-surgical chemotherapy plans based on Signatera results. The majority of oncologists found that Signatera results strengthened the treatment plan under consideration, and surveillance with Signatera enabled a high rate of curative-intent surgery among recurrent patients.
Tissue-Free MRD Detection
Natera also presented initial results from a clinical performance study on its novel tissue-free MRD detection test. The study demonstrated high sensitivity and specificity in patients evaluable for clinical outcomes. MRD-positive patients showed inferior recurrence-free survival, and benefited from adjuvant therapy, while MRD-negative patients did not. The tissue-free MRD test showed strong concordance with the gold standard Signatera test, with a positive percent agreement of 86% (95% CI:77-93%) and a negative percent agreement of 98% (95% CI: 95-100%).
John Paul Y.C. Shen, MD, from the University of Texas MD Anderson Cancer Center, presented a poster on the development of a methylation-based, tissue-agnostic test for MRD detection by circulating tumor DNA.
Early Cancer Detection Data
Case-control data in early cancer detection, including data from screen-detected colorectal cancer cases from the CIRCULATE study and controls from the PROCEED-CRC study, were also presented. The data reported an overall sensitivity of 95% (95% CI: 92-99%) and a specificity of 91% (95% CI: 88-94%). Among patients with stage I disease, sensitivity was 92% overall, and stage-adjusted sensitivity was 91% in screen-detected individuals.
Yoshiaki Nakamura, MD, PhD, from the National Cancer Center Hospital East, presented a poster on the performance of a blood-based screening test for the early detection of colorectal cancer.
Expert Commentary
"This data at ASCO GI demonstrates the ongoing strength of Signatera complemented by our exciting innovation pipeline," said Adham Jurdi, MD, senior medical director in oncology at Natera. "The results from BESPOKE CRC highlight the potential value of Signatera-based MRD detection for treatment-decision making, with strong findings in clinical utility. Our readouts in early cancer detection and tissue-free MRD offer great promise for expanding Natera’s portfolio to help millions of additional patients with cancer."
