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

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Author Affiliations

JAMA. 2021;325(13):1277-1286. doi:10.1001/jama.2021.2454

Question  Does the cyclooxygenase 2 inhibitor celecoxib, when added to standard adjuvant chemotherapy, improve disease-free survival among patients with stage III colon cancer?

Findings  In this randomized clinical trial that involved 2526 patients, the addition of celecoxib for 3 years, compared with placebo, to standard adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) did not significantly improve disease-free survival (76.3% vs 73.4% at 3 years; hazard ratio for disease recurrence or death, 0.89).

Meaning  Among patients with stage III colon cancer, the addition of celecoxib, compared with placebo, to standard adjuvant chemotherapy did not significantly improve disease-free survival.

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: 

Source: //jamanetwork.com/journals/jama/article-abstract/2778113?guestAccessKey=afbf2467-8129-4626-957e-ec04c2c4df11&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_content=etoc&utm_term=040621