Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer: The CALGB/SWOG 80702 (Alliance) Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association 2021-04, Vol.325 (13), p.1277-1286
• Main Authors: Meyerhardt, Jeffrey A, Shi, Qian, Fuchs, Charles S, Meyer, Jeffrey, Niedzwiecki, Donna, Zemla, Tyler, Kumthekar, Priya, Guthrie, Katherine A, Couture, Felix, Kuebler, Philip, Bendell, Johanna C, Kumar, Pankaj, Lewis, Dequincy, Tan, Benjamin, Bertagnolli, Monica, Grothey, Axel, Hochster, Howard S, Goldberg, Richard M, Venook, Alan, Blanke, Charles, O’Reilly, Eileen M, Shields, Anthony F
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Adjuvant therapy; Adjuvants; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Aspirin; Cancer; Cancer therapies; Celecoxib; Celecoxib - adverse effects; Celecoxib - therapeutic use; Chemotherapy; Chemotherapy, Adjuvant; Clinical trials; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - surgery; Colorectal cancer; COX-2 inhibitors; Creatinine; Cyclooxygenase 2 Inhibitors - adverse effects; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase-2; Death; Disease-Free Survival; Factorial design; Fatalities; Female; Health services; Humans; Hypertension; Leukemia; Male; Medical treatment; Middle Aged; Mortality; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - prevention & control; Neoplasm Staging; Original Investigation; Oxaliplatin; Patient Compliance; Patients; Placebos; Polyps; Proportional Hazards Models; Randomization; Risk management; Secondary Prevention; Survival; Survival Rate; Treatment Failure; Young Adult
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.2021.2454

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 tr