A data analysis of a randomized clinical trial for stage 3 colon cancer patients by researchers at the Dana-Farber Brigham Cancer Center found that patients with evidence of residual cancer in their blood after surgery to remove the cancer may benefit from the addition of celecoxib to their post-surgery treatment. The analysis showed that patients with blood tests positive for circulating tumor DNA (ctDNA) had worse overall outcomes, but those who were treated with celecoxib, a nonsteroidal anti-inflammatory drug, experienced significantly improved disease-free survival.
“This is one of the first studies to show that ctDNA status has predictive utility in terms of selecting patients who will respond best to a medication,” says Jonathan Nowak, MD, PhD, pathologist at Dana-Farber Cancer Institute and Brigham and Women’s Hospital who is presenting the study at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium on January 25, 2025 in San Francisco, California.
“These results add to our previous findings that celecoxib improves survival for PIK3CA-mutated colon cancer,” says Jeffrey Meyerhardt, MD, MPH, senior author and co-director of the Colon and Rectal Cancer Center at Dana-Farber Cancer Institute. “These findings will help to develop a personalized approach to adjuvant therapy for patients with early-stage colon cancer.”
Patients with stage 3 colon cancer are initially treated with surgery to remove the cancer in the colon and nearby lymph nodes. After this treatment, they typically receive adjuvant chemotherapy aimed at reducing their risk of the cancer returning. However, in a subset of these patients, the cancer returns, which can make them incurable. A key research focus at Dana-Farber is to find ways to improve adjuvant therapies and prevent recurrence.
To investigate the use of celecoxib in disease-free survival in patients with stage 3 colon cancer, Meyerhardt and colleagues launched a randomized clinical trial, the CALGB (alliance)/SWOG 80702 trial, in 2010 with the Alliance for Clinical Trials in Oncology and the National Cancer Institute. The trial enrolled 2,526 patients between 2010 and 2015. After treatment, patients were randomly assigned to receive adjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) for three or six months with or without daily celecoxib for three years. Those who took celecoxib showed a modest benefit, but the results, which were published in 2021, were not statistically significant.
Since then, evidence has emerged suggesting that anti-inflammatory drugs could benefit some patients with colon cancer, but not others. One possibility for this is that patients who have a blood test shortly after surgery that shows evidence of ctDNA have a higher risk of relapse and may benefit from additional therapies beyond standard chemotherapy. In this new study, the researchers wanted to explore whether anti-inflammatory drugs could help prevent relapse in patients whose ctDNA test was positive shortly after surgery.
When the original prospective celecoxib clinical trial was designed a decade ago, patients were evaluated before and after surgery using imaging, which reveals where cancer cells have clustered, but has limited resolution. ctDNA testing available today provides a more sensitive read on whether cancer remains after surgery by detecting microscopic fragments of tumor DNA in the blood.
The study team identified 1,011 of 2,526 patients who had participated in the original trial and had agreed to have blood drawn for research purposes that were available for analysis. They performed ctDNA testing on blood samples taken after surgery. This analysis revealed that patients with positive ctDNA generally had worse outcomes. However, those with positive ctDNA tests who were prescribed celecoxib, in addition to standard chemotherapy, had significantly improved disease-free survival compared to those who received only standard chemotherapy. For those who had negative ctDNA tests, there were no significant differences between those who took celecoxib versus placebo.
“Based on this analysis, the benefits of celecoxib with chemotherapy appear promising for patients with early-stage colon cancer with positive ctDNA after primary treatment,” the researchers say. “This evidence plus the results of other ongoing studies will help to determine which patients may benefit from celecoxib in addition to other standard treatments.”