As reported in JAMA by Jeffrey A. Meyerhardt, MD, MPH, FASCO, and colleagues, the phase III CALGB/SWOG 80702 (Alliance) trial has shown no disease-free survival benefit with the addition of the cyclooxygenase 2 (COX-2) inhibitor celecoxib to standard adjuvant therapy in patients with stage III colon cancer.
As stated by the investigators, “Aspirin and COX-2 inhibitors have been associated with a reduced risk of colorectal polyps and cancer in observational and randomized studies. The effect of celecoxib as treatment for nonmetastatic colon cancer is unknown.”
Jeffrey A. Meyerhardt, MD, MPH, FASCO
Study Details
The 2 × 2 factorial design trial included 2,524 patients from sites in the United States and Canada. They were randomly assigned between June 2010 and November 2015 to receive FOLFOX (fluorouracil, leucovorin, and oxaliplatin) every 2 weeks for 3 vs 6 months with blinded random assignment to 3 years of celecoxib at 400 mg daily (n = 1,263) or placebo (n = 1,261). The current report presents results of the celecoxib random assignment. The primary endpoint was disease-free survival.
Disease-Free Survival
Adherence with study treatment—defined as receiving celecoxib or placebo for more than 2.75 years or continuing treatment until disease recurrence, death, or unacceptable adverse events—was 70.8% in the celecoxib group and 69.9% in the placebo group.
Median follow-up for surviving patients was 6.0 years. In the disease-free survival analysis, median observation times were 4.1 years (interquartile range [IQR] = 1.6–5.3 years) for the celecoxib group and 4.0 years (IQR = 1.4–5.2 years) for the placebo group. Median disease-free survival was not reached in either group; disease-free survival at 3 years was 76.3% (95% CI = 73.8%–78.8%) for the celecoxib group vs 73.4% (95% CI = 70.8%–76.0%) for the placebo group (hazard ratio [HR] = 0.89, 95% CI = 0.76–1.03, P = .12). The effect of celecoxib on disease-free survival did not vary significantly according to assigned duration of FOLFOX treatment (P for interaction = .61).
In overall survival analysis, median observation times were 5.5 years (IQR = 4.0–6.1 years) for the celecoxib group and 5.5 years (IQR = 3.8–6.0 years) for the placebo group. Median overall survival was not reached in either group; overall survival at 5 years was 84.3% (95% CI = 82.2%–86.5%) in the celecoxib group vs 81.6% (95% CI = 79.4%–83.9%) in the placebo group (HR = 0.86, 95% CI = 0.72–1.04, P = .12). The effect of celecoxib on overall survival did not vary significantly according to assigned duration of FOLFOX treatment (P for interaction = .79).
KEY POINTS
- The addition of celecoxib to adjuvant chemotherapy did not improve disease-free survival.
- No improvement in overall survival was observed.
Adverse Events
During FOLFOX treatment, grade ≥ 3 adverse events occurred in 51.7% of patients in the celecoxib group and 50.8% of the placebo group, with the most common including decreased neutrophils (31.3% vs 32.0%) and peripheral neuropathy (10.3% vs 9.1%). Among potential celecoxib-related adverse events, any-grade hypertension occurred in 14.6% vs 10.9% of patients (P = .01) during FOLFOX treatment and in 13.0% vs 10.0% (P = .04) after FOLFOX treatment. Grade ≥ 2 creatinine increase following FOLFOX treatment was also significantly more common in the celecoxib group (1.7% vs 0.5%, P = .01). After FOLFOX therapy, grade 3 or 4 peripheral neuropathy occurred in 4.9% vs 4.1% of patients.
The investigators concluded, “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.”
Dr. Meyerhardt, of the Dana-Farber Cancer Institute, is the corresponding author for the JAMA article.
Disclosure: The study was supported by National Cancer Institute grants, Pfizer, and others. For full disclosures of the study authors, visit jamanetwork.com.
