Signatera Assay Identifies Benefit of Celecoxib in Resected Colorectal Cancer

An exploratory biomarker analysis from the randomized, phase 3 CALGB (Alliance)/SWOG 80702 trial (NCT01150045) demonstrated that circulating tumor DNA (ctDNA)–based minimal residual disease (MRD) status, as assessed by the Signatera assay, was predictive of benefit from the addition of adjuvant celecoxib (Celebrex) in patients with resected colorectal cancer.^1,2

The analysis revealed a statistically significant interaction between MRD status and treatment assignment, indicating that the effect of celecoxib differed according ctDNA positivity per the Signatera assay. In ctDNA-positive patients, adding celecoxib to conventional adjuvant chemotherapy following surgery reduced the risk of cancer recurrence and death by approximately 40% compared with placebo. Specifically, celecoxib significantly improved disease-free survival (DFS; adjusted HR, 0.61; 95% CI, 0.42-0.89), with 3-year DFS rates of 41.0% vs 22.6%, respectively, and overall survival (OS; adjusted HR, 0.62; 95% CI, 0.40-0.96), with 5-year OS rates of 61.6% vs 39.9%, respectively.

Data from further analyses showed that the benefit of celecoxib in ctDNA-positive patients was independent of demographic, pathologic, and molecular characteristics, including PIK3CA mutation status. Improvements in DFS were observed among ctDNA-positive patients with PIK3CA wild-type tumors (adjusted HR, 0.64; 95% CI, 0.42-0.98) as well as those with PIK3CA-altered tumors (adjusted HR, 0.19; 95% CI, 0.06-0.58). In contrast, no DFS benefit was observed with celecoxib in ctDNA-negative patients, regardless of PIK3CA status (PIK3CA wild-type adjusted HR, 0.80; 95% CI, 0.55-1.18; PIK3CA-altered adjusted HR, 0.85; 95% CI, 0.33-2.24).

These findings build on previously reported DFS data that were presented at the 2025 Gastrointestinal Cancers Symposium.

“For patients with detectable ctDNA after surgery, adding celecoxib to standard chemotherapy improved both DFS and OS,” Jonathan Nowak, MD, PhD, an investigator a the Hale Family Center for Pancreatic Cancer Research, an associate pathologist at Brigham and Women’s Hospital, and an associate professor of pathology at Harvard Medical School, all in Boston, Massachusetts, and corresponding author of the publication stated in a news release.¹ “In addition to highlighting Signatera’s predictive abilities in this setting, the publication also underscores its value as a prognostic marker for disease recurrence and survival.”

What was the design of CALGB (Alliance)/SWOG 80702 study?

The CALGB (Alliance)/SWOG 80702 trial was designed to evaluate whether cyclooxygenase-2 (COX-2) inhibition with celecoxib could improve survival outcomes in patients with colon cancer.³ Patients were eligible if they had resected stage III colon adenocarcinoma without evidence of metastatic disease and at least 1 pathologically confirmed positive lymph node or N1c disease, as defined by American Joint Committee on Cancer version 7 criteria. Key exclusion criteria included regular use of nonsteroidal anti-inflammatory drugs more than twice weekly or aspirin at doses exceeding 325 mg more than 3 times per week; however, use of low-dose aspirin at doses of 100 mg per day or less was permitted.

Eligible patients were randomly assigned to receive celecoxib at 400 mg daily or placebo in combination with either 6 or 12 cycles of FOLFOX (leucovorin calcium, fluorouracil, and oxaliplatin). This resulted in 4 treatment arms: placebo plus 12 cycles of FOLFOX, celecoxib plus 12 cycles of FOLFOX, placebo plus 6 cycles of FOLFOX, or celecoxib plus 6 cycles of FOLFOX. Study treatment with celecoxib or placebo was continued for up to 3 years from initiation.

The trial planned to enroll 2500 patients; a total of 2526 patients were enrolled, with 2524 included in the final analysis. The primary end point was DFS. In the prespecified primary analysis, celecoxib did not significantly improve DFS compared with placebo (HR, 0.89; 95% CI, 0.76-1.03; stratified log-rank P = .12), and no differential effect was observed based on the duration of adjuvant FOLFOX therapy.

“This publication marks another important milestone in colorectal cancer research, highlighting Signatera as a critical tool in disease management,” Adham Jurdi, MD, senior medical director of GI oncology at Natera, shared in a news release.¹ “It further demonstrates Signatera’s predictive utility in identifying, with great precision, patients with MRD who will likely benefit from celecoxib in addition to chemotherapy, regardless of their PIK3CA status.”

References

1. Natera announces publication of Signatera™ analysis from randomized, phase III CALGB (Alliance)/SWOG 80702 study in colorectal cancer. News Release. Natera. December 18, 2025. Accessed December 18, 2025. https://www.natera.com/company/news/natera-announces-publication-of-signatera-analysis-from-randomized-phase-iii-calgb-alliance-swog-80702-study-in-colorectal-cancer/
2. Meyerhardt JA, Twombly T, Pederson L, Ma C, O’Reilly EM, Shields AF. Predictive role of circulating tumor DNA in stage III colon cancer treated with celecoxib. JAMA Oncology. Published online December 4, 2025. doi:10.1001/jamaoncol.2025.5144 ‌
3. Meyerhardt JA, Shi Q, Fuchs CS, et al. Effect of celecoxib vs placebo added to standard adjuvant therapy on disease-free survival among patients with stage II colon cancer: the CALGB/SWOG 80702 (Alliance) randomized clinical trial. JAMA. 2021;325(13):1277-1286. doi:10.1001/jama.2021.2454
4. Nowak JA, Shi Q, Twombly T, et al. Prognostic and predictive role of circulating tumor DNA (ctDNA) in stage III colon cancer treated with celecoxib: findings from CALGB (Alliance)/SWOG 80702. J Clin Oncol. 2025;43(4):LBA14. doi:10.1200/JCO.2025.43.4_suppl.LBA14