A new data analysis from a randomized clinical trial conducted by investigators at Dana-Farber Cancer Center and Brigham and Women’s Hospital suggests that patients with stage 3 colon cancer who show evidence of residual cancer in their blood after surgery may benefit from adding celecoxib, a non-steroidal anti-inflammatory drug (NSAID), to their post-surgery treatment regimen. The study, presented by Jonathan Nowak, MD, PhD, at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium on January 25, 2025, highlights the potential of circulating tumor DNA (ctDNA) as a predictive biomarker for treatment selection.
“This is one of the first predictive uses of ctDNA testing that we have for selecting adjuvant therapy in colorectal cancer,” said Jeffrey Meyerhardt, MD, MPH, co-director of the Colon and Rectal Cancer Center at Dana-Farber Cancer Institute and the senior author of the study. The findings build on the team’s prior research that demonstrated the potential of celecoxib in improving survival for patients with PIK3CA-mutated colon cancer.
The CALGB/SWOG 80702 trial
Patients diagnosed with stage 3 colon cancer typically undergo surgery to remove the tumor and affected lymph nodes, followed by adjuvant chemotherapy to lower the risk of recurrence. However, for a subset of patients, cancer returns despite standard treatment.
To evaluate the role of celecoxib in disease-free survival, the research team launched the CALGB (Alliance)/SWOG 80702 clinical trial in 2010 in collaboration with the Alliance for Clinical Trials in Oncology and the National Cancer Institute. Between 2010 and 2015, the trial enrolled 2,526 patients who were randomized to receive fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy for three or six months, with or without daily celecoxib for three years.
While the initial results published in 2021 indicated a moderate benefit for celecoxib, they were not statistically significant. “While there appeared to be a slight benefit of receiving celecoxib versus placebo, it hinted that there was probably a subgroup of patients that really benefited from celecoxib,” added Meyerhardt. The team had a theory that patients who were positive for ctDNA right after surgery might be a group that would benefit from the drug. This is based on the fact that for the past eight to nine years, the colorectal cancer community has been aware that the presence of ctDNA after curative intent surgery is highly prognostic.
The team undertook this analysis to test this theory and determine whether ctDNA could identify patients at higher risk for recurrence and who might benefit from additional therapy with celecoxib.
Key findings
The research team analyzed blood samples from 1,011 consented patients from the original 2,526 patients who had participated in the original trial. The results revealed that:
- 189 patients (18.7%) had ctDNA-positive blood samples, indicating a higher risk of recurrence, shorter disease-free survival, and overall survival.
- After three years, 86.6% of ctDNA-negative patients remained disease-free, compared to 36.8% of ctDNA-positive patients.
- Patients with ctDNA-negative results did not experience a significant difference in disease-free survival whether they received celecoxib or a placebo.
- Among ctDNA-positive patients, those who took celecoxib had significantly improved disease-free survival compared to those who received a placebo.
- After three years, 44.1% of ctDNA-positive patients who took celecoxib showed no cancer recurrence, compared to 26.6% of those who received a placebo.
- ctDNA-positive patients who took celecoxib had a 37% lower risk of all-cause mortality compared to those who did not receive the drug.
“Our results suggest that a blood-based biomarker test looking at ctDNA to see if any tumor cells remain right after a patient has surgery could help determine whether they should take an oral drug that may prevent cancer recurrence,” said Nowak, a pathologist at Dana-Farber Cancer Institute and Brigham and Women’s Hospital.
Meyerhardt added, “There really is a significant benefit to taking celecoxib in the adjuvant setting only if a patient is ctDNA-positive at baseline.”
The research team plans to explore additional biomarkers to help identify patients who would benefit most from celecoxib. They will also investigate whether longer chemotherapy durations improve outcomes for ctDNA-positive patients and further examine how COX-2 inhibition reduces inflammation to prevent colon cancer recurrence.
