A recent data analysis from a randomized phase III clinical trial indicates that adding celecoxib to the treatment regimen of stage III colon cancer patients after surgery may significantly improve outcomes for those with residual cancer traces detectable in their blood. The study, presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium, highlights the potential of circulating tumor DNA (ctDNA) as a predictive biomarker.
The CALGB (Alliance)/SWOG 80702 trial, which initially enrolled 2,526 patients between 2010 and 2015, assessed the benefit of adding celecoxib, a non-steroidal anti-inflammatory drug (NSAID), to FOLFOX chemotherapy in the postoperative treatment of stage III colorectal cancer (CRC). While the original trial results, published in 2021, did not show a significant improvement in disease-free survival with celecoxib, subsequent analyses revealed potential benefits in specific CRC subgroups.
ctDNA as a Predictive Biomarker
Jeffrey Meyerhardt, MD, MPH, senior author and co-director of the Colon and Rectal Cancer Center at Dana-Farber Cancer Institute, noted that the original trial used imaging techniques with limited ability to detect microscopic cancer clusters. Current ctDNA tests offer a more sensitive approach by identifying tiny fragments of tumor DNA in the blood.
The new data analysis included 1,011 patients from the original trial with available post-surgery biobanked samples. Researchers used the Signatera™ ctDNA test to identify patients who might benefit from celecoxib in addition to FOLFOX chemotherapy.
Improved Disease-Free Survival with Celecoxib
The analysis revealed that patients with positive ctDNA tests generally had worse outcomes. However, those with positive ctDNA tests who received celecoxib with standard chemotherapy experienced significantly improved disease-free survival compared to those who received a placebo. For patients with negative ctDNA tests, there was no significant difference between those taking celecoxib versus placebo.
Jonathan Nowak, MD, PhD, lead author and molecular and gastrointestinal pathologist at Dana-Farber Cancer Institute and Brigham and Women's Hospital, stated, "These findings highlight the critical role of ctDNA status in predicting cancer recurrence and chemotherapy benefit for patients with stage III colon cancer. For those with detectable traces of cancer in their blood after surgery, adding celecoxib to their treatment regimen may significantly improve disease-free survival, offering a new opportunity to enhance outcomes for this high-risk group."
Personalized Approach to Adjuvant Therapy
The study suggests that ctDNA testing could help identify patients who would benefit most from celecoxib, allowing for a more personalized approach to adjuvant therapy. "This is one of the first studies to show that ctDNA status has predictive utility in terms of selecting patients that respond better to a drug," said Dr. Nowak.
The researchers plan to explore additional biomarkers to further refine patient selection for celecoxib treatment and investigate whether longer chemotherapy durations improve outcomes for ctDNA-positive patients.
