According an updated analysis of a substudy of the GALAXY trial, ctDNA-based detection of minimal residual disease (MRD) and ctDNA dynamics in response to adjuvant chemotherapy for colorectal cancer were highly prognostic of patient outcomes.

These results were presented by Hiroki Yukami, MD, Osaka Medical and Pharmaceutical University, Takatsuki, Japan, at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium on Saturday, January 20, 2024, in San Francisco, California.

As previously reported, the observational GALAXY study demonstrated post surgical detection of MRD to be prognostic of patient outcomes and the most significant risk factor for recurrence regardless of BRAF V600E status. In this updated analysis, the correlation between ctDNA dynamics and patient outcomes among patients with radically resected,  stage II to IV colorectal cancer was evaluated.

Of the 3034 total patients in the GALAXY study, 2518 were deemed eligible and included in this substudy. Detection and quantification of ctDNA was done via the Signatera assay from samples collected at 1, 3, 6, 9, 12, 18, and 24 months following surgery until recurrence. Following the curative-intent surgery, patients received either adjuvant chemotherapy (n = 1000) or observation (n= 1518). The primary end point for this substudy was disease-free survival (DFS).

The median follow-up was 16. 3 months. There were 2093 patients with ctDNA results available, 309 who were ctDNA-positive and 1784 who were ctDNA-negative. Those patients who were ctDNA-positive during the MRD window had a significantly inferior DFS than those who were ctDNA-negative (hazard ratio [HR], 15.75; 95% confidence interval [CI], 12.59 to 19.68; P < .0001). Those patients who remained ctDNA-positive 3 months following the detection of MRD were more than 5 times more likely to recur when compared to those patients who experienced ctDNA clearance (HR, 5.4; 95% CI, 3.58 to 7.67%; P < .0001). Of the patients with subsequent ctDNA data points available, 68 patients had sustained while 58 eventually returned ctDNA patients. Those patients who were sustained ctDNA-negative had significantly better outcomes than those patients with transient ctDNA clearance (HR, 32.57; 95% CI, 9.94 to 106.76; P < .0001). Additionally, among those patients who were ctDNA-positive and received adjuvant chemotherapy, a ≥50% decrease in ctDNA levels at the 6-month point were associated with better DFS when compared with those patients who had a >50% decrease, or in increase in ctDNA levels.

Dr Yukami concluded, “These findings may allow us to spare a considerable number of ctDNA-negative patients the toxicity of chemotherapy without compromising their long-term survival and identify ctDNA-positive patients who should receive chemotherapy.” Dr Yukami went on, “Monitoring ctDNA during surveillance allows for early detection of cancer recurrence, which can potentially enable early intervention, improve the chances of a cure, and/or extend survival.”

ASCO expert, Cathy Eng, MD, added, “This is the first study to not only demonstrate the significance of sustained ctDNA clearance, but also that a dynamic change in ctDNA of more than 50% at 6 months of adjuvant chemotherapy was associated with improved disease-free survival.”

Source:

Yukami H, Nakamura Y, Mishima S, et al. Circulating tumor DNA (ctDNA) dynamics in patients with colorectal cancer (CRC) with molecular residual disease: Updated analysis from GALAXY study in the CIRCULATE-JAPAN. Presented at 2024 ASCO Gastrointestinal Cancer Symposium; January 18-20, 2024; San Francisco, California. Abstract 6

Will Patients With Molecular Residual Disease Detected After Surgery for Colorectal Cancer Benefit from Adjuvant Chemotherapy? ctDNA May Hold the Answer. ASCO. January 16, 2024. https://old-prod.asco.org/about-asco/press-center/news-releases/will-patients-molecular-residual-disease-detected-after