The use of a ctDNA assay could help determine which patients with colorectal cancer may benefit most from chemotherapy after surgery.
The presence of circulating tumor DNA (ctDNA) — which can be determined via blood test — may help identify which patients with colorectal cancer will benefit most from post-surgical (adjuvant) chemotherapy, according to findings from the GALAXY study, which were presented at the 2022 ASCO Gastrointestinal Cancers Symposium.
“Our study shows that stratifying post-surgical treatment decisions using the assay can identify patients likely to benefit from (adjuvant chemotherapy) across all stages,” Dr. Masahito Kotaka, from Gastrointestinal Cancer Center, Sano Hospital, in Japan said during the presentation.
ctDNA is the DNA from tumors that enter the bloodstream. Previous research has shown that when it is detected — thus determining a patient’s results to be ctDNA-positive —the individual may be at a higher risk for recurrence.
Patients with high-risk stage 2 disease and ctDNA-positive status at four weeks experienced a six-month disease-free survival (time after primary treatment ends that a patient survives without any signs or symptoms of the cancer) rate of 100% with adjuvant chemotherapy, compared with 53.8% for those without ctDNA. In stage 3 disease, those rates were 89.2% and 32%, respectively. For stage 4 disease, adjuvant chemotherapy use in patients with positive ctDNA status resulted in six-month disease-free survival (DFS) rates of 72.7% vs 28.3% for without ctDNA.
A total of 1,564 patients were enrolled to GALAXY between June 5, 2020, and April 30, 2021. Of whom 1,040 were included in the current analysis (Outcome cohort). After excluding ineligible patients, investigators further divided the cohorts into patients who were ctDNA positive (183 patients), known as the Clearance cohort, and ctDNA negative (531 patients) four-weeks post-surgery.
The Outcome cohort was majority male in both the ctDNA positive and negative groups (51% vs 62%), with stage 3 cancer occurring most frequently (36% vs 48%). Patients with negative vs positive ctDNA were more likely to harbor BRAF V600E mutations (9% vs 3%) or have microsatellite instability (MSI)–high tumors (12% vs 3%).
For patients with stage 1 to 4 disease and who were ctDNA-negative four weeks after surgery, the six-month disease-free survival rate was 96.5%, while the 12-month disease-free survival rate was 92.7%.
Those with ctDNA positivity had significantly worse outcomes, with DFS rates of 62.8% and 47.5% at the six- and 12-month marks, respectively.
Limiting the analysis to patients with stage 2 to 4 disease indicated that six- and 12-month rates of disease-free survival favored the negative vs positive cohorts, as well, at 97.8% vs 73% and 95.2% vs 55.5%, respectively.
The highest risk of recurrence for patients with stage 2 to 3 cancer was correlated with four-weeks post-surgery ctDNA positive, mutant RAS or mutant BRAF.
Investigators then performed an analysis which excluded patients who recurred within 12 weeks of surgery, called the Dyanmics analysis cohort (838 patients), to evaluate how predictive ctDNA is for this population’s adjuvant chemotherapy outcomes.
The six-month DFS rate for those with ctDNA-negative status at the four-week time point and negative status at the 12-week point was 100% vs 98% with ctDNA negative/negative ctDNA, 62.5% for negative to positive ctDNA, and 58.3% for ctDNA positive/positive.
Cumulative clearance of ctDNA at six months after surgery was higher amongst those who received adjuvant chemotherapy compared with no chemotherapy, at rates of 68% vs 10%, respectively. An analysis of patients with stage 2 to 4 disease showed the risk of recurrence was significantly increased between those with and without adjuvant chemotherapy and RAS mutant vs wild-type status.
The 12-month DFS rate for those who received adjuvant chemotherapy and had high-risk stage 2 cancer was 88.9% vs 46.2% without. In stage 3 disease, the 12-month DFS rates were 68.3% vs 24.0%, respectively. For stage 4, corresponding rates were 53.7% vs 22.3%.
In the ctDNA-negative cohort treated with adjuvant vs no chemotherapy, patients were 50% male, had performance status of 0, meaning that their cancer did not affect their activities of daily living, and had stage 3 cancer (83% vs 41%). Those treated with adjuvant chemotherapy had six- and 12-month DFS rates of 98.6% and 96.2% compared with 97.5% and 94.7% for those without chemotherapy.
“ctDNA-guided adjuvant strategy will further be established by ongoing randomized VEGA and ALTAIR studies and will be presented in the future conferences,” Kotaka concluded.
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