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Although ctDNA positivity generally meant worse disease-free survival in stage 3 resected colon cancer, patients with ctDNA who received Celebrex had significantly better rates versus placebo.
(ctDNA) positivity after surgery for stage 3 colon cancer predicted poorer disease-free survival, but patients with ctDNA who received Celebrex had better rates than those on placebo.
While positive circulating tumor DNA (ctDNA) predicted poorer disease-free survival (DFS) in stage 3 resected colon cancer, Celebrex (celecoxib) significantly improved DFS outcomes in ctDNA-positive patients compared to placebo, as demonstrated in results from a subgroup analysis of the phase 3 CALGB (Alliance)/SWOG 80702 trial presented at the 2025 Gastrointestinal Cancers Symposium.
Among patients with ctDNA-negative colon cancer following surgery and before treatment with Celebrex or placebo (767 patients), the estimated three-year DFS rate was 86.5%. Among those with ctDNA-positive disease (173 patients), this estimated rate was 33.7%.
“In a subset of patients enrolled in CALGB/SWOG 80702, ctDNA status after surgery and prior to starting adjuvant therapy was highly prognostic of DFS and overall survival [OS],” Dr. Jonathan Nowak, lead study author, said in a press briefing ahead of the presentation of the data. “Additionally, ctDNA status appeared predictive of the benefit of adjuvant [Celebrex].”
Nowak is an investigator at the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute and an assistant professor of pathology at Harvard Medical School in Boston.
Circulating tumor DNA: DNA from tumors that is found in the bloodstream.
Disease-free survival: the length of time a person lives after completing treatment without any signs or symptoms of the disease returning.
Adjuvant therapy: treatment given after the main treatment to reduce the risk for cancer recurrence.
Overall survival: the length of time from diagnosis or treatment initiation that a patient with cancer is still alive.
When patients were stratified by treatment with Celebrex versus placebo, investigators showed that patients with ctDNA-negative disease at the time of study enrollment had similar outcomes regardless of whether they received Celebrex or placebo, with estimated three-year DFS rates of 87.4% and 85.6%, respectively. However, among patients with ctDNA-positive disease, a significant DFS benefit was seen in the Celebrex arm versus the placebo arm, with estimated 3-year DFS rates of 41% versus 22.6%, respectively.
“Approximately one-third of patients diagnosed with colon cancer have regional lymph node involvement,” Nowak said. “Despite optimal surgery and adjuvant chemotherapy, approximately 20% to 70% of patients with stage 3 disease will have a recurrence. Additional strategies beyond standard chemotherapy are needed to reduce risk of recurrent disease and improve survival. One promising option is to use post-resection ctDNA status, which can tell us if any residual micrometastatic disease is present in order to help guide adjuvant treatment decisions.”
Prior research has shown that patients with colon cancer and colon cancer survivors who receive aspirin or COX-2 inhibitors experience favorable DFS and OS outcomes. For instance, a prospective, observational study showed that among 843 evaluable patients with stage 3 colon cancer who were enrolled in an adjuvant chemotherapy trial, those who used COX-2 inhibitors had improved five-year DFS rate and OS rate compared with nonusers.
The CALGB/SWOG 80702 trial formally tested whether COX-2 inhibition with Celebrex improved survival in patients with colon cancer. To be eligible for trial enrollment, patients needed to have resected stage 3 colon adenocarcinoma without metastatic disease, and at least one pathologically confirmed positive lymph node. Patients were not eligible for enrollment if they used nonsteroidal anti-inflammatory drugs at any dose more often than two times per week or aspirin more than 325 milligrams three times per week. However, patients using low-dose aspirin not exceeding a dose of 100 milligrams per day were permitted to enroll.
Patients were randomly assigned to receive daily treatment with either Celebrex or placebo in combination with either six or 12 treatments of FOLFOX (leucovorin calcium, fluorouracil and oxaliplatin) as follows: placebo plus 12 FOLFOX treatments (arm A), Celebrex plus 12 FOLFOX treatments (arm B), placebo plus six FOLFOX treatments (arm C) or Celebrex plus six FOLFOX treatments (arm D). Celebrex or placebo was continued for three years from study drug initiation.
The trial had a target sample size of 2,500 patients; 2,526 total patients were enrolled, and 2,524 patients were included.3 DFS served as the trial’s primary end point. In the primary analysis, investigators observed no statistically significant DFS difference with Celebrex versus placebo. Furthermore, the effects of Celebrex treatment were not significantly different based on assigned adjuvant FOLFOX duration.
In the Gastrointestinal Cancers Symposium analysis, Nowak noted that information regarding DFS in the primary analysis indicated that a subgroup of patients may derive benefit from adjuvant Celebrex.
To identify whether any patient subgroup derived greater benefit from Celebrex treatment compared with the overall population, investigators retrospectively performed a ctDNA analysis using the Signatera minimal residual disease assay on banked plasma specimens from trial patients that were collected after surgery and before trial enrollment.
Nowak highlighted that findings from this subgroup analysis “also held true in multivariable adjusted models for both DFS and OS when the factors that are commonly known to predict colon cancer survival [were] included in the model.”
In the multivariable analysis, among ctDNA-negative patients, Celebrex reduced the risk for cancer returning by 24% compared with placebo, although it was not statistically significant. Regarding OS, Celebrex also reduced the risk for death by 16% compared with placebo, though these findings were also not statistically significant.
In ctDNA-positive patients, findings related to both DFS and OS were statistically significant. In particular, compared with placebo, Celebrex reduced the risk for cancer recurrence and for death each by 37%.
Nowak concluded by explaining that sensitivity and subgroup analyses of this trial are ongoing, as well as studies evaluating the predictive value of ctDNA for three versus six months of adjuvant FOLFOX in this patient population.
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