Results from a post hoc analysis published in JAMA Oncology in December 2025 confirm that a new blood test can help doctors determine which patients with colorectal cancer should receive anti-inflammatory medication alongside chemotherapy after surgery.[1]
The study, supported, in part, by the National Cancer Institute (NCI) and by Pfizer and Natera, was based on a clinically validated, tumor-informed assay from an Alliance for Clinical Trials in Oncology trial, assessed circulating tumor DNA (ctDNA) status in 940 patients* with stage III colon cancer and found that ctDNA negativity was strongly associated with improved survival. The study outcomes showed that patients with ctDNA positivity demonstrated a survival benefit with adjuvant celecoxib, whereas patients with ctDNA negativity did not.
These findings could lead to more personalized treatments and better outcomes for patients.
Colorectal cancer
According to data from the American Cancer Society (ACS), colorectal cancer is one of the most common cancers in the United States, with about 110,000 new cases diagnosed each year. Even after surgery and chemotherapy, up to 40% of patients with stage III disease see their cancer return.
Celecoxib (Celebrex®, Viatris; Elyxyb® SCILEX Pharmaceuticals)** belongs to a class of medicines known as nonsteroidal anti-inflammatory drugs or NSAIDs, which include common drugs such as aspirin and ibuprofen. Celecoxib, a prescription NSAID, is often used to reduce pain from arthritis. The drug inhibits COX-2-enzymes, which produce prostaglandins that are mainly involved in inflammation.
Researchers have suspected that the anti-inflammatory properties in NSAIDs could prevent colorectal cancer from coming back since inflammation plays a role in cancer growth. However, clinical trials have not shown a clear benefit for all patients, leaving doctors unsure who should take them.
New data
This new analysis offers insight. Researchers looked at ctDNA, tiny fragments of cancer DNA that can remain in the blood after surgery. Patients who tested positive for ctDNA after surgery were much more likely to have their cancer return. For these high-risk patients, adding celecoxib to chemotherapy significantly improved survival. Patients without ctDNA did not benefit, which means that they could avoid taking extra medication unnecessarily.
To measure ctDNA, clinicians draw a simple blood sample from the patient and use gene sequencing to analyze it.
“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 circulating tumor DNA levels after surgery using this blood test has the potential to change that,” explained lead study author George Zhang, MD, MPH, a general surgery resident at Brigham and Women’s Hospital.
Study
“The main goal of CALGB (Alliance)/SWOG 80702 was to determine if adding celecoxib to chemotherapy after surgery for colorectal cancer improved survival,” noted study chair Jeffrey Meyerhardt, MD, MPH, a medical oncologist at the 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 chemo after surgery,” Meyerhardt added.
With support from the National Cancer Institute, CALGB (Alliance)/SWOG 80702 enrolled more than 2,500 patients with stage III colorectal cancer who had initially had surgery to remove their tumor. This study examined ctDNA biospecimens from 940 individuals.
In patients who tested ctDNA-positive, the addition of celecoxib compared with placebo nearly doubled disease-free survival over three years: 41% versus 22.6%. Over five years, the overall survival for patients who were ctDNA-positive was 61.6% with celecoxib, compared with 39.9% in the placebo group.
“Although these results are very encouraging, additional prospective research will be necessary to further validate them,” Zhang concluded.
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Noted: * The study enrolled 940 patients, and included 767 patients who were ctDNA negative and 173 who were ctDNA positive.
** Celecoxib is chemically designated as 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide and is a diaryl-substituted pyrazole. Celecoxib selectively inhibits cyclooxygenase-2 (COX-2), which is responsible for prostaglandin synthesis and is integral to the pain and inflammation pathway. [2] This activity gives celecoxib its analgesic, anti-inflammatory, and antipyretic effects. In addition, celecoxib weakly inhibits cyclooxygenase-1 (COX-1) and affects platelet function less than aspirin. Finally, celecoxib has selective anticancer properties by binding to cadherin-11 (CDH11), which plays a significant role in the malignant progression of cancer cells.[3]
Clinical trials
Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer (PATINA) – ClinicalTrials.gov ID NCT02947685.
Highlights of Prescribing Information
Celecoxib (Celebrex®, Viatris)[Prescribing Information]
Celecoxib (Elyxyb® SCILEX Pharmaceuticals)
Reference
[1] Zhang GQ, Meyerhardt JA, Shi Q, Twombly T, Pederson L, Ma C, Väyrynen JP, Zhao M, Takashima Y, Shergill A, Kumar P, Couture F, Kuebler P, Krishnamurthi S, Tan B, O’Reilly EM, Giannakis M, Ogino S, Jurdi A, Sharma S, Aleshin A, Shields AF, Nowak JA. Predictive Role of Circulating Tumor DNA in Stage III Colon Cancer Treated With Celecoxib: A Post Hoc Analysis of the CALGB (Alliance)/SWOG 80702 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2025 Dec 4:e255144. doi: 10.1001/jamaoncol.2025.5144. Epub ahead of print. PMID: 41343176; PMCID: PMC12679421. [JAMA Oncology]
[2] McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):272-7. doi: 10.1073/pnas.96.1.272. Erratum in: Proc Natl Acad Sci U S A 1999 May 11;96(10):5890. PMID: 9874808; PMCID: PMC15129.
[3] Assefnia S, Dakshanamurthy S, Guidry Auvil JM, Hampel C, Anastasiadis PZ, Kallakury B, Uren A, Foley DW, Brown ML, Shapiro L, Brenner M, Haigh D, Byers SW. Cadherin-11 in poor-prognosis malignancies and rheumatoid arthritis: common target, common therapies. Oncotarget. 2014 Mar 30;5(6):1458-74. doi: 10.18632/oncotarget.1538. PMID: 24681547; PMCID: PMC4039224.
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