Natera has released new data from the GALAXY arm of its ongoing CIRCULATE-Japan trial showing the efficacy of its molecular residual disease (MRD) detection test in predicting overall survival (OS) in patients with resectable colorectal cancer (CRC).
Signatera is an MRD detection test that uses circulating DNA (ctDNA) to detect and quantify cancer left in the body, as well as identify recurrence earlier than standard-of-care tools. The new analysis provides the first evidence of the ability of Signatera-based MRD detection to predict OS, per the company.
The results were presented as part of the 2024 Congress of the European Society for Medical Oncology (ESMO) taking place from 13 to 17 September in Barcelona, Spain. Natera is also publishing the analysis in the Nature Medicine journal.
The study monitored 2,240 patients with stage II-IV CRC who used Signatera after curative-intent surgery. Signatera-positivity in the post-op MRD window was found to be significantly associated with worse OS compared to Signatera-negative patients with a 36-month OS.
Researchers noted that: “this 10x advantage in overall survival compares favourably to all known guideline-recommended biomarkers that have HRs for overall survival in a range of 1-4”.
The test was also able to predict the OS benefit of using adjuvant chemotherapy (ACT) post-surgery. High-risk stage II and stage III-IV patients who were Signatera-positive after surgery and received ACT demonstrated superior OS, corresponding to a 50% reduction in the risk of death when treated with ACT. There was no such ACT-associated OS benefit was seen in Signatera-negative patients.
Signatera's positivity was associated with an increased risk of recurrence. Only 16.7% of Signatera-positive patients remained disease-free at 36 months, compared to 83.5% of Signatera-negative patients.
Sustained Signatera-negative and ctDNA clearance was associated with a superior survival benefit with 24-month OS of 100%. Patients who cleared ctDNA for some time but later became Signatera-positive had a 24-month OS of 82% while the patients who did not achieve ctDNA clearance had a 24-month OS of 61%.
“Introducing 36-month, first-of-its-kind data on overall survival is an important milestone that reinforces the potential to improve outcomes for patients diagnosed with colorectal cancer,” said Minetta Liu, chief medical officer of oncology at Natera.
“The updated data affirms ctDNA status as a critical measure both for prognosis and for predicting which patients may truly benefit from adjuvant chemotherapy.”
Natera has made strides in expanding the use of the Signatera test in multiple cancer indications including ovarian and muscle-invasive bladder cancer. However, the company has been embroiled in an ongoing patent infringement litigation with CareDx for its DNA amplification technology.
