Circulating tumor DNA (ctDNA) levels may help to determine which patients with colon cancer could benefit from the addition of nonsteroidal anti-inflammatory drugs (NSAIDs), such as celecoxib, to chemotherapy following surgery, according to findings from a post hoc analysis of the CALGB/SWOG 80702 phase III trial that was published in JAMA Oncology.
“We’ve known that NSAIDs may help prevent recurrence in some patients with colon cancer, but until now, we didn’t know how to identify them. Measuring ctDNA levels after surgery using this blood test has the potential to change that,” said lead study author George Q. Zhang, MD, MPH, General Surgery Resident at Brigham and Women’s Hospital.
The study authors believe that this finding could lead more personalized treatment approaches for patients.
Background and Study Methods
In select patients with colon cancer, observational studies have suggested a possible association between aspirin and selective cyclooxygenase inhibitors and decreased recurrence.
Researchers wanted to assess the value of postoperative ctDNA for predicting survival outcomes when patients with stage III colon cancer received adjuvant celecoxib with conventional chemotherapy. They completed a post hoc analysis of patients from the phase III CALGB (Alliance)/SWOG 80702 clinical trial that explored the use of adjuvant celecoxib vs placebo plus 3 or 6 months of adjuvant chemotherapy of 5-fluouracil, leucovorin, and oxaliplatin. ctDNA positivity was assessed with a tumor-informed 16-plex polymerase chain reaction/next-generation sequencing assay that was completed in between surgery and the start of adjuvant therapy.
“The main goal of CALGB (Alliance) 80702 was to determine if adding celecoxib to chemotherapy after surgery for colon cancer improved survival,” said study chair Jeffrey Meyerhardt, MD, MPH, medical oncologist at Dana-Farber Cancer Institute. “The initial trial didn’t definitively confirm our hypothesis; however, we saw that some patients did benefit from adding celecoxib, and we then sought to identify them. This study identified a subset of patients that had detectable ctDNA after surgery as a group that benefited from adding celecoxib to chemotherapy after surgery.”
Key Findings
Only 18.4% of patients were ctDNA-positive, which was found to be associated with worse disease-free survival (adjusted hazard ratio [aHR] = 6.12; 95% confidence interval [CI] = 4.66–8.03) as well as overall survival (aHR = 5.86; 95% CI = 4.19–8.19).
Among these patients, celecoxib use was associated with 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) vs placebo.
Comparatively, patients with ctDNA negativity who received celecoxib did not benefit from the added therapy in terms of disease-free survival (aHR = 0.76; 95% CI = 0.53–1.09; P = .41) or overall survival (aHR = 0.85; 95% CI = 0.54–1.36; P = .33).
This trend continued even when patients were stratified by microsatellite instability status and PIK3CA status.
“Although these results are very encouraging, additional prospective research will be necessary to further validate them,” Dr. Zhang added.
Disclosure: This work was supported by the National Cancer Institute in addition to Pfizer and Natera. For full disclosures of the study authors, visit jamanetwork.com.
