Natera, Inc., has unveiled new findings from the GALAXY arm of the CIRCULATE-Japan trial at the 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain. GALAXY, one of the largest studies of its kind, focuses on circulating tumor DNA (ctDNA) testing in patients with resectable colorectal cancer (CRC).
This latest analysis, also set to be published in Nature Medicine, provides compelling evidence that Natera’s Signatera test, which detects molecular residual disease, can predict overall survival for CRC patients. Additionally, the study shows Signatera’s ability to identify which patients may benefit most from adjuvant chemotherapy based on ctDNA clearance, a marker of improved survival outcomes.
The study followed 2,240 patients with stage II-IV CRC for a median of 23 months after surgery. The key findings include:
- Predictive Value for Overall Survival: Patients who tested positive for Signatera in the post-surgical MRD window were found to have significantly worse overall survival compared to those who tested negative. Over a 36-month period, Signatera-positive patients had an OS rate of 71.8%, compared to 96.0% for those who were Signatera-negative. This represents a nearly 10-fold increase in the risk of death for patients with positive results.
- Benefit from Adjuvant Chemotherapy: High-risk stage II and stage III-IV patients who were Signatera-positive after surgery and underwent ACT had a 50% lower risk of death compared to those who did not receive chemotherapy, according to the study. In contrast, patients who were Signatera-negative did not show a significant survival benefit from ACT.
- Signatera as a Recurrence Predictor: Post-surgery, Signatera-positivity was the most significant predictor of recurrence and overall survival, outperforming all other clinical and pathological risk factors. Over three years, disease-free survival for Signatera-negative patients was 83.5%, while it dropped to 16.7% for those who tested positive.
- Impact of ctDNA Clearance: Patients who achieved and maintained ctDNA clearance after chemotherapy had a 100% overall survival rate at 24 months, compared to 61% for patients who did not clear ctDNA. Those who experienced “transient clearance” (where ctDNA clearance was achieved but later became positive) had an OS rate of 82%.
Dr. Yoshiaki Nakamura, principal investigator of the study from the National Cancer Center Hospital East in Japan, emphasized the significance of the findings: “This large-scale trial shows a clear connection between MRD status and overall survival in colorectal cancer. Signatera offers a precise way to predict outcomes, which could revolutionize personalized cancer treatment.”
Dr. Minetta Liu, chief medical officer of oncology at Natera, highlighted the importance of these results: “Introducing 36-month data on overall survival is a crucial step forward, further validating ctDNA testing as an essential tool for prognosis and identifying which patients will benefit most from adjuvant chemotherapy.”