TOPLINE:

Postoperative circulating tumor DNA (ctDNA) positivity strongly predicts worse survival in stage III colon cancer, with ctDNA-positive patients showing sixfold higher recurrence risk. Among ctDNA-positive patients, celecoxib improves 3-year disease-free survival to 41.0% vs 22.6% with placebo.

METHODOLOGY:

• Considerable evidence suggests that aspirin and nonsteroidal anti-inflammatory drugs protect against development of colorectal adenomas and subsequent progression to colorectal cancer. Additionally, observational studies have shown that aspirin or nonsteroidal anti-inflammatory drug use after colorectal cancer diagnosis is associated with lower recurrence risk.
• Despite the well-established prognostic value of ctDNA, its role in guiding treatment decisions remains unclear.
• Researchers conducted a post hoc analysis of the phase 3 Cancer and Leukemia Group B/Southwest Oncology Group 80702 randomized clinical trial (2010-2015) involving 940 patients with stage III colon cancer.
• Analysis included postoperative ctDNA testing using a clinically validated, tumor-informed 16-plex-polymerase chain reaction-next-generation sequencing assay performed between surgery and adjuvant therapy initiation.
• Participants were randomized to receive either celecoxib, 400 mg daily, or placebo for 3 years, along with either 3 or 6 months of adjuvant fluorouracil, leucovorin, and oxaliplatin.
• Primary outcome measures included disease-free survival and overall survival, with a median follow-up of 6.0 years (95% CI, 6.0-6.0).

TAKEAWAY:

• Among the study cohort, 81.6% were ctDNA negative and 18.4% were ctDNA positive, with ctDNA positivity associated with worse disease-free survival (adjusted hazard ratio [AHR], 6.12; 95% CI, 4.66-8.03) and overall survival (AHR, 5.86; 95% CI, 4.19-8.19).
• Celecoxib treatment in ctDNA-positive patients improved disease-free survival (AHR, 0.61; 95% CI, 0.42-0.89) and overall survival (AHR, 0.62; 95% CI, 0.40-0.96) compared with placebo.
• In ctDNA-negative patients, celecoxib showed no significant survival benefit (disease-free survival: AHR, 0.76; 95% CI, 0.53-1.09; overall survival: AHR, 0.85; 95% CI, 0.54-1.36).
• Results remained consistent across subgroups stratified by microsatellite instability status and PIK3CA mutational status.

IN PRACTICE:

“These findings underscore the prognostic value of ctDNA and suggest it may help identify a subset of patients who benefit most from adjuvant COX-inhibition alongside conventional chemotherapy and may offer opportunities for personalized approaches in CRC [colorectal cancer] treatment,” the authors of the study wrote.

SOURCE:

This study was led by George Q. Zhang, MD, MPH, Department of Surgery, Brigham and Women’s Hospital in Boston, and Jeffrey A. Meyerhardt, MD, MPH, Department of Medical Oncology, Dana-Farber Cancer Institute in Boston. It was published online on December 4 in JAMA Oncology.

LIMITATIONS:

According to the authors, this was a post hoc analysis of existing clinical trial data and may be confounded by lack of randomization within ctDNA subgroups. Additionally, ctDNA was only measured at one time point prior to therapy initiation, preventing assessment of ctDNA clearance with adjuvant therapy. The study population may not fully represent the broader disease population, with an overrepresentation of patients who self-reported as White race and non-Hispanic ethnicity.

DISCLOSURES:

This research was funded by grants from the National Cancer Institute of the US National Institutes of Health, the Alliance for Clinical Trials in Oncology Foundation, Pfizer, and Natera. Qian Shi, PhD, reported receiving consulting fees from multiple pharmaceutical companies including Bayer HealthCare, Boehringer Ingelheim, and Bristol Myers Squibb, along with institutional grants from various organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.