Natera, Inc. (NASDAQ: NTRA), a leader in transforming care through genetic and cell-free DNA testing, today announced the publication of a new study in Clinical Cancer Research demonstrating the ability of its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, to assess tumor growth rates and predict patient survival in early-stage colorectal cancer (CRC). The full study can be found here.
In previous studies, Signatera was validated to detect early-stage CRC recurrence 8.7 months earlier than CT imaging (median lead time), simply based on positive or negative MRD status.1 Without treatment, more than 98% of MRD-positive patients go on to relapse.1-4 This new study replicates that previous test performance in a larger, multi-center cohort; but it also demonstrates that MRD-positive patients can be further stratified based on the quantity of circulating tumor DNA (ctDNA) found in the blood, in particular, how quickly those levels grow over time (ctDNA growth rate, or ctDNA velocity).
Every Signatera test report contains positive/negative MRD status as well as the mean number of tumor molecules observed per mL of plasma (MTM/mL). With serial testing, these quantities can be compared over time to calculate ctDNA velocity, a unique metric that Natera will make available to its customers.
"This study, the largest of its kind in stage III CRC, demonstrates that personalized and tumor-informed ctDNA analysis offers more value than just a positive or negative result," said Dr. Andres Cervantes, professor of medical oncology at the University of Valencia, Spain, and senior author of the study. "The novel combination of ctDNA detection and growth rate assessment provides unique opportunities for guiding clinical decision making."
The publication describes a prospectively collected, multicenter study of 168 stage III CRC patients undergoing curative-intent treatment, with longitudinal MRD assessment before and after surgery, and then at regular intervals throughout adjuvant chemotherapy (ACT) and surveillance for up to 3 years (n=1204 samples).
Key findings from the study include:
- Patients who remain MRD-positive after completion of ACT were highly likely to recur (HR 50.80), with a median lead time of 9.8 months ahead of radiographic recurrence
- MRD-positive patients with slow-growing tumors (average 27% ctDNA-increase per month) experienced OS similar to those who did not relapse at all (3-year OS 100%); while patients with fast-growing tumors (average 137% increase per month) experienced poor outcomes with 3-year OS 37.5%
- Persistent ctDNA clearance during and after ACT was strongly associated with good outcomes (100% 3-year RFS), while transient ctDNA clearance during ACT was associated with poor prognosis (0% 3-year RFS)
"It's intuitive that the amount of ctDNA in a patient's blood is a proxy for the tumor burden," said Dr. Alexey Aleshin, Natera's VP of medical affairs, oncology. "What's exciting here is that the ctDNA velocity is such a strong predictor of patient survival, which can help oncologists to further stratify their MRD-positive patients as they consider the appropriate management strategy."
Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for both clinical and research use and has been granted three Breakthrough Device Designations by the FDA for multiple cancer types and indications. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual's tumor. This maximizes Signatera's accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. Signatera is intended to detect and quantify how much cancer is left in the body, to detect recurrence earlier, and to help optimize treatment decisions.
Signatera test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers. Signatera has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP-accredited, ISO 13485 certified, and CLIA certified.
Natera is a pioneer and global leader in cell-free DNA testing from a simple blood draw. The mission of the company is to change the management of disease worldwide with a focus on women's health, oncology, and organ health. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in San Carlos, California, and Austin, Texas. It offers proprietary genetic testing services to inform obstetricians, transplant physicians, oncologists, and cancer researchers, including biopharmaceutical companies, and genetic laboratories through its cloud-based software platform.