Dr Nakamura on the Association Between MRD Negativity and DFS in Resected CRC

Yoshiaki Nakamura, MD, PhD, National Cancer Center Hospital Japan East, discusses updated findings from an analysis of the association between circulating tumor DNA (ctDNA) minimal residual disease (MRD) status and disease-free survival (DFS) in the GALAXY trial, an observational arm of the ongoing CIRCULATE-Japan trial (UMIN000039205) in patients with resected colorectal cancer (CRC).

At the 2023 ESMO Congress, Nakamura presented results from an updated 24-month DFS analysis in patients with stage II to IV radically resected CRC from the GALAXY trial. In this trial, the MRD window was 2 to 10 weeks post-surgery prior to initiating any adjuvant therapy. The ctDNA dynamics were measured from the MRD window until 3 months post-surgery. In these updated results, ctDNA MRD positivity was associated with shorter DFS rates (HR, 12.46; 95% CI, 9.85-15.76; P < 2.0e-16), which was consistent with previously reported data from this trial, Nakamura says.

This analysis of ctDNA MRD dynamics showed that patients with persistently negative ctDNA MRD levels had the highest DFS rates, followed by those who converted to ctDNA MRD negativity, those who converted to ctDNA MRD positivity, and those who had persistently positive ctDNA MRD levels, with respective 24-month DFS rates of 90.3% (95% CI, 88.1%-92.1%), 53.9% (95% CI, 42.1%-64.3%), 20.7% (95% CI, 4.7%-44.5%), and 9.8% (95% CI, 4.4%-17.7%). The respective DFS hazard ratios in the converted negative, converted positive, and persistently positive cohorts were 6.06 (95% CI, 4.18-8.79; P < 2.0e-16), 12.7 (95% CI, 7.57-21.3; P < 2.0e-16), and 38.4 (95% CI, 27.94-52.78; P < 2.0e-16). Patients who converted from negative to positive ctDNA MRD levels were classified as high-risk, and they should receive specific interventions, Nakamura emphasizes.

Additionally, an evaluation of the benefit of adjuvant chemotherapy showed that in the ctDNA-negative cohort, the 24-month DFS rates were 88.3% (95% CI, 84.4%-91.2%) in patients who received adjuvant chemotherapy vs 89.9% (95% CI, 87%-92.1%) in those who did not (HR, 1.39; 95% CI, 0.88-2.20; P = .156). In the ctDNA-positive cohort, the 24-month DFS rates were 38.6% (95% CI, 29.6%-47.5%) in patients who received adjuvant chemotherapy vs 16.1% (95% CI, 6%-30.6%) in those who did not (HR, 3.29; 95% CI, 2.13-5.07; P = .6.9e-08).

Editor’s Note: Dr Nakamura reports honoraria from Chugai and Guardant Health AMEA; and research grants from Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Seagen, and Roche Diagnostics.