Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer
Year: 2021
Type: article
Study design: Clinical Trial
Abstract: Importance: Aspirin and cyclooxygenase 2 (COX-2) inhibitors have been associated with a reduced risk of colorectal polyps and cancer in observational and randomized studies. The effect of celecoxib, a COX-2 inhibitor, as treatment for nonmetastatic colon cancer is unknown. Objective: To determine if the addition of celecoxib to adjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) improves disease-free survival in patients with stage III colon cancer. Design, Setting, and Participants: Cancer and Leukemia Group B (Alliance)/Southwest Oncology Group 80702 was a 2 × 2 factorial design, phase 3 trial conducted at 654 community and academic centers throughout the United States and Canada. A total of 2526 patients with stage III colon cancer were enrolled between June 2010 and November 2015 and were followed up through August 10, 2020. Interventions: Patients were randomized to receive adjuvant FOLFOX (every 2 weeks) for 3 vs 6 months with or without 3 years of celecoxib (400 mg orally daily; n = 1263) vs placebo (n = 1261). This report focuses on the results of the celecoxib randomization. Main Outcomes and Measures: The primary end point was disease-free survival, measured from the time of randomization until documented recurrence or death from any cause. Secondary end points included overall survival, adverse events, and cardiovascular-specific events. Results: Of the 2526 patients who were randomized (mean [SD] age, 61.0 years [11 years]; 1134 women [44.9%]), 2524 were included in the primary analysis. Adherence with protocol treatment, defined as receiving celecoxib or placebo for more than 2.75 years or continuing treatment until recurrence, death, or unacceptable adverse events, was 70.8% for patients treated with celecoxib and 69.9% for patients treated with placebo. A total of 337 patients randomized to celecoxib and 363 to placebo experienced disease recurrence or died, and with 6 years' median follow-up, the 3-year disease-free survival was 76.3% for celecoxib-treated patients vs 73.4% for placebo-treated patients (hazard ratio [HR] for disease recurrence or death, 0.89; 95% CI, 0.76-1.03; P = .12). The effect of celecoxib treatment on disease-free survival did not vary significantly according to assigned duration of adjuvant chemotherapy (P for interaction = .61). Five-year overall survival was 84.3% for celecoxib vs 81.6% for placebo (HR for death, 0.86; 95% CI, 0.72-1.04; P = .13). Hypertension (any grade) occurred while treated with FOLFOX in 14.6% of patients in the celecoxib group vs 10.9% of patients in the placebo group, and a grade 2 or higher increase in creatinine levels occurred after completion of FOLFOX in 1.7% vs 0.5% of patients, respectively. Conclusions and Relevance: Among patients with stage III colon cancer, the addition of celecoxib for 3 years, compared with placebo, to standard adjuvant chemotherapy did not significantly improve disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01150045.
Source: JAMA
Authors: Jeffrey A. Meyerhardt, Qian Shi, Charles S. Fuchs, Jeffrey Meyer, Donna Niedzwiecki, Tyler Zemla, Priya Kumthekar, Katherine A. Guthrie, Felix Couture, Philip Kuebler, Johanna C. Bendell, Pankaj Kumar, Dequincy Lewis, Benjamin Tan, Monica Bertagnolli, Axel Grothey, Howard S. Hochster, Richard M. Goldberg, Alan Venook, Charles Blanke, Eileen M. O’Reilly, Anthony F. Shields
Institutions: Mayo Clinic, Yale Cancer Center, Yale University, Smilow Cancer Hospital, Duke Medical Center, Northwestern Medicine, Fred Hutch Cancer Center, Hôtel-Dieu de Québec, National Cancer Institute, Tennessee Oncology, Illinois CancerCare, Cone Health, Washington University in St. Louis, Brigham and Women's Hospital, West Cancer Center, Rutgers Cancer Institute, West Virginia University, West Virginia University Hospitals, University of California, San Francisco, Oregon Health & Science University, SWOG Cancer Research Network, OHSU Knight Cancer Institute, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, Weill Cornell Medical Center, Wayne State University, The Barbara Ann Karmanos Cancer Institute
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1044130170, Alliance Statistics and Data Management Center, ECOG-ACRIN Network Group Operations Center, G1938688226, G1946161885, G2424276686, G3053988604, Yale Cancer Center NCTN LAPS, G3475623468, Network Lead Academic Participating Site: Memorial Sloan Kettering Cancer Center, SWOG Network Group Operations Center of the NCTN, G4185274752, NRG Oncology Network Group Operations Center, NCTN Lead Academic Participating Site at Dana-Farber/Partners Cancer Care, ECOG-ACRIN Network Group Statistics and Data Management Center, Johns Hopkins University NCTN Lead Academic Site Program, G848463896, Alliance for Clinical Trials in Oncology Operations Center, Cancer Center Support Grant, Yale Clinical and Translational Science Award
OpenAlex ID: W3144575654