image: The Alliance for Clinical Trials in Oncology is a national leader in advancing cancer research, uniting more than 25,000 cancer specialists at 115 main institutions and 1,400 affiliate centers across the U.S. and Canada. As part of the National Clinical Trials Network and a leading research base for the NCI Community Oncology Research Program, the Alliance conducts pioneering, practice-changing clinical trials that improve outcomes and reshape standards of care. Our work has led to multiple FDA approvals, influenced national guidelines, and produced hundreds of high-impact publications. More than 40,000 participants have taken part in Alliance studies, and our growing biospecimen repository now includes more than 1.5 million samples, collected over the past 30 years. Learn more at www.AllianceforClinicalTrialsinOncology.org.
Credit: Alliance for Clinical Trials in Oncology
A blood test could help doctors decide which patients with colon cancer should receive anti-inflammatory medication along with chemotherapy after surgery, according to new study in JAMA Oncology. Based on data from an Alliance for Clinical Trials in Oncology study, this finding could lead to more personalized treatments and better outcomes for patients.
Colon cancer is one of the most common cancers in the United States with about 110,000 new cases diagnosed each year, according to the American Cancer Society. Even after surgery and chemotherapy, up to 40% of patients with stage III disease see their colon cancer return. Celecoxib belongs to a class of medicines known as NSAIDs (nonsteroidal anti-inflammatory drugs), which include common drugs like aspirin and ibuprofen. Celecoxib is a prescription NSAID often used to reduce pain from arthritis.
Researchers have suspected that the anti-inflammatory properties in NSAIDs could prevent colon 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.
This new analysis offers insight. Researchers looked at circulating tumor DNA (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, meaning they could avoid taking extra medication unnecessarily. To measure ctDNA, clinicians take a simple blood test from the patient and use gene sequencing to analyze the sample.
“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,” said lead study author George Q. Zhang, MD, MPH, a general surgery resident at Brigham and Women’s Hospital.
“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, 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.”
With support from the National Cancer Institute, CALGB (Alliance) 80702 enrolled more than 2,500 patients with stage III colorectal cancer who had initially had surgery to remove their tumor. This study looked at the ctDNA biospecimens of 940 individuals – 767 of whom were ctDNA negative and 173 that were ctDNA positive. In patients who tested ctDNA positive, the addition of celecoxib compared to placebo nearly doubled disease-free survival over three years, 41% compared to 22.6%. Over five years, the overall survival for patients who were ctDNA positive was 61.6% for those who received celecoxib, compared to 39.9% in those in the placebo group.
“Although these results are very encouraging, additional prospective research will be necessary to further validate them,” Dr. Zhang added.
# # #
In addition to the NCI, this work was supported in part by Pfizer and Natera.
References: CALGB (Alliance) 80702—A phase III trial of 6 versus 12 treatments of adjuvant FOLFOX plus celecoxib or placebo for patients with resected stage III colon cancer
JAMA Oncology: 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
The Alliance for Clinical Trials in Oncology is a national leader in advancing cancer research, uniting more than 25,000 cancer specialists at 115 main institutions and 1,400 affiliate centers across the U.S. and Canada. As part of the National Clinical Trials Network and a leading research base for the NCI Community Oncology Research Program, the Alliance conducts pioneering, practice-changing clinical trials that improve outcomes and reshape standards of care. Our work has led to multiple FDA approvals, influenced national guidelines, and produced hundreds of high-impact publications. More than 40,000 participants have taken part in Alliance studies, and our growing biospecimen repository now includes more than 1.5 million samples, collected over the past 30 years. Learn more at www.AllianceforClinicalTrialsinOncology.org.
Journal
JAMA Oncology
Method of Research
Randomized controlled/clinical trial
Subject of Research
People
Article Title
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
Article Publication Date
4-Dec-2025
COI Statement
Conflict of Interest Disclosures: Dr Shi reported consulting fees from Bayer HealthCare Boehringer Ingelheim, Yiviva, Regeneron, Hoosier Cancer Research Network, Kronos Bio Mirati Therapeutics Genmab US HopeAI Bristol Myers Squibb, AbbVie, BeOne Medicines, Exelixis, and Agenus; and institutional grants from Regeneron, Bristol Myers Squibb, Roche/Genentech, Janssen, Novartis, and MPAACT, all outside the submitted work. Dr Shergill reported advisory board fees from Guardant during the conduct of the study; and advisory board for Iterion Therapeutics, Revolution Medicine, Ipsen, Merus, Guardant, Pfizer, Regeneron/Sanofi, and Catalyst Pharmaceuticals; honorarium/travel/ lodging fees from Cure CRC Summit, Great Debates in GI Oncology, Takeda, OncLive, OSCO/ASCO Direct, ACPMP, Cholangiocarcinoma Summit, Cholangiocarcinoma Foundation, ASCO Advantage, and ASCO; and institutional grants from Hutchison MediPharma, Takeda, Merck, Verastem Oncology, Turning Point Therapeutics, Gritstone, Bolt Therapeutics, Bristol Myers Squibb, Pfizer, Astellas, Oncologie, Macogenics, Seattle Genetics, Amgen, Daiichi, Lilly, Jacobio, AstraZeneca, Jazz Pharma, and AbbVie. Dr Krishnamurthi reported grants from the National Cancer Institute to Case Comprehensive Cancer Center during the conduct of the study. Dr O’Reilly reported institutional grants from Genentech/Roche, BioNTech, AstraZeneca, Arcus, Elicio Therapeutics, Parker Institute, National Institutes of Health/National Cancer Institute, Digestive Care, Break Through Cancer, Agenus, Amgen, and Revolution Medicines; consulting fees or uncompensated service to Arcus, Amgen, AstraZeneca, Ability Pharma, Alligator BioSciences, Pfizer, Agenus, BioNTech, Ipsen, Ikena, Merck, Moma Therapeutics, Novartis, Astellas, Bristol Myers Squibb, Revolution Medicines, Regeneron, Tango Therapeutics, and Pfizer; travel fees from BioNTech and Arcus; and grants from the American Association of Cancer Research, American Society of Clinical Oncology, Imedex, Research To Practice, and Stand Up To Cancer, and the National Institutes of Health/National Cancer Institute. Dr Giannakis reported grants from Janssen and Sunbird Bio, and personal fees from Nerviano Medical Sciences, PER, and OncLive outside the submitted work. Dr Ogino reported grants from National Institutes of Health and the American Cancer Society during the conduct of the study; consulting fees from Sanofi Pasteur outside the submitted work. Dr Sharma equity holdings in Natera. Dr Aleshin reported equity holdings in Natera. Dr Nowak reported grants from Natera during the conduct of the study. No other disclosures were reported. Funding/Support: This research was funded by in whole or in part by the National Cancer Institute of the US National Institutes of Health (NIH) under (award No. U10 CA180821, U10 CA180882, U24 CA196171 to the Alliance for Clinical Trials in Oncology]; UG1CA189830, UG1CA233180, UG1CA233339, UG1CA233290, U10CA180863 and CCS 707213 [CCTG]; U10CA180794, U10CA180820 [ECOG-ACRIN]; U10CA180868 [NRG Oncology]; U10CA180888 and UG1CA233163 [SWOG]). Additional support provided to the Alliance for Clinical Trials in Oncology Foundation at https:// pubs.alliancefound.org/acknowledgments. It is subject to the NIH public access policy. Through acceptance of this federal funding, NIH has been given a right to make the author accepted manuscript publicly available in PubMed Central on the official date of publication, as defined by NIH. In addition, the work was supported by Karen Guo Colon Cancer Fund, Project P, Douglas Gray Woodruff Chair in Colorectal Research Fund, Stone Research Fund, NIH (grant No. T32CA009001 to Dr Zhang), and in part by the American Cancer Society Clinical Research Professor Award (No. CRP-24-1185864-01-PROF to Dr Ogino). This research was also supported in part by Pfizer and Natera through the Alliance for Clinical Trials in Oncology Foundation, as part of a correlative science proposal (CSC0218) approved by the National Clinical Trials Network Core Correlative Sciences Committee. Role of the Funder/Sponsor: Nonfederal sponsors did not contribute to design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The National Cancer Institute provided grant and administrative support to the trial, was involved in the design of the study and in the review and final approval of the manuscript. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.