Signatera MRD Test Predicts Overall Survival in Colorectal Cancer, GALAXY Study Shows

Key Insights

• Signatera, a ctDNA-based MRD test, demonstrates its ability to predict overall survival in resectable colorectal cancer patients, marking a significant advancement in personalized medicine.
• The GALAXY study reveals that Signatera-positive patients receiving adjuvant chemotherapy experienced a 50% reduction in the risk of death, highlighting the test's predictive value for chemotherapy benefit.
• Signatera status is identified as the most significant predictor of recurrence, outperforming standard clinicopathologic risk factors, with a notably higher hazard ratio for both DFS and OS.

New data from the GALAXY arm of the CIRCULATE-Japan trial, presented at the 2024 ESMO Congress, demonstrates that Natera's Signatera molecular residual disease (MRD) test can predict overall survival (OS) in patients with resectable colorectal cancer (CRC). The study, involving 2,240 patients, also showed Signatera's ability to predict which patients would benefit from adjuvant chemotherapy (ACT). The findings are poised to be published in Nature Medicine.

The GALAXY study monitored patients with stage II-IV CRC using Signatera after surgery intended to cure the cancer. With a median follow-up of 23 months, the study revealed that Signatera-positivity was significantly associated with worse OS compared to Signatera-negative patients (HR: 9.68, p < 0.01). Specifically, the 36-month OS was 71.80% for Signatera-positive patients versus 96.0% for Signatera-negative patients.

Adjuvant Chemotherapy Benefit

The study indicated that high-risk stage II and stage III-IV patients who were Signatera-positive after surgery and received ACT demonstrated superior OS (adjusted HR: 0.53, p = 0.05), which translates to a 50% reduction in the risk of death. In contrast, Signatera-negative patients did not show a significant OS benefit from ACT (adjusted HR: 0.53, p = 0.13).

Recurrence Prediction

Signatera-positivity after surgery was identified as the most significant prognostic factor associated with inferior DFS (HR 12.08, p < 0.01) and OS (HR 9.87, p < 0.01) in a multivariate analysis. The 36-month DFS difference between Signatera-positive and Signatera-negative patients was 16.7% (95% CI: 12.1–21.9%) versus 83.5% (95% CI: 81.2–85.6%), respectively.

Sustained ctDNA Clearance

Patients who achieved sustained ctDNA clearance and remained Signatera-negative had a 24-month OS of 100%. In comparison, patients with transient ctDNA clearance had a 24-month OS of 82%, and those who did not achieve ctDNA clearance had a 24-month OS of 61%.

"We now have compelling prospective evidence from a large trial of more than 2,200 patients that clearly reinforces the link between MRD status and overall survival," said Yoshiaki Nakamura, MD, PhD, principal investigator of the study. "These findings suggest that Signatera can predict post-surgical outcomes for colorectal cancer patients with great precision."

Minetta Liu, MD, chief medical officer of oncology at Natera, added, "The updated data affirms ctDNA status as a critical measure both for prognosis and for predicting which patients may truly benefit from adjuvant chemotherapy."