Minimal residual disease, as detected by circulating tumor DNA (ctDNA; fragments of cancer genetic material found in the bloodstream) helped determine the risk of recurrence and response to postsurgical chemotherapy in patients with stage 2/3 colorectal cancer, according to early findings from a subset of patients enrolled in the BESPOKE clinical trial.
These data were recently presented at the 2024 Gastrointestinal Cancers Symposium.
“BESPOKE is one of the first and largest studies in the United States looking at a tumor-informed circulating tumor DNA’s ability to inform adjuvant chemotherapy decisions in patients with both stage 2 and 3 colorectal cancer,” Dr. Pashtoon Murtaza Kasi, medical oncologist and researcher at Weill Cornell Medicine and New York-Presbyterian Hospital, said in his presentation.
Of 295 evaluable patients with stage 2 (130 patients) and stage 3 (165 patients) CRC, 6.9% (46 patients) of stage 2 and 22.4% (37 patients) of stage 3 patients were MRD-positive as identified by ctDNA, meaning that cancer was detected in the blood.
There was a significant association between MRD positivity and worse disease-free survival (DFS; time until relapse or death) outcomes overall, as well as within the stage 2 and stage 3 groups.
The median DFS was not reached post-surgery among patients who were MRD-negative vs a median DFS of 15.98 months (range, 13.77 to 20.22) in patients who were MRD-positive.
Among patients who were MRD-positive, those who received postsurgical chemotherapy experienced longer DFS compared with those in the observation group (18.7 versus 6.7). Comparatively, there was no observed benefit to DFS with adjuvant chemotherapy in the MRD-negative group.
“Regardless of the fact if you got (chemotherapy or) didn't get (chemotherapy, there were) very intriguing results: (the) same disease-free survival of nearly nine months. A benchmark for the pairing of novel therapeutics and clinical trial designs on a large cohort of patients with stage 2 and 3 colon cancer,” Kasi explained.
ctDNA clearance, which shows that there are no detectable cancer mutations in the blood, at 12 weeks was observed in 39.1% (18 patients) of patients who were MRD-positive, and longer DFS was associated with ctDNA clearance compared with those who remained positive (24.2 months versus 13.8 months). However, these patients still had worse DFS than those who were ctDNA-negative at four and 12 weeks.
Disease recurrence was observed in 44.4% (eight) of patients who had ctDNA clearance, and all eight patients were ctDNA-positive before relapse was detected radiologically.
“We also show some very interesting dynamics of ctDNA clearance. The ones who sustain clearance, not surprisingly, are the ones who are all disease-free several years out before the ones who are not transiently clear. Interestingly, 85% of the time, you have molecular recurrence by 15 months. So, as we counsel patients or expect what to see in trials, 15 months is the time point from any kind of molecular recurrence,” Kasi said.
Kasi also highlighted that ctDNA testing provided patients with more feelings of confidence. A reported 73% of patients said that ctDNA results reduced anxiety about cancer recurrence, and 87% felt they were receiving the right treatment after receiving their ctDNA results. Moreover, 92% of patients would continue using ctDNA testing to monitor cancer, and 96% valued the additional information they received from ctDNA results.
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