The addition of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to standard adjuvant chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) failed to significantly improve disease-free survival (DFS) or overall survival (OS) compared with placebo in patients with stage III colon cancer, according to the results of the phase 3 CALGB/SWOG 80702 (Alliance) trial published in JAMA.
The trial (ClinicalTrials.gov Identifier: NCT01150045), which used a 2 x 2 factorial design, evaluated the superiority of celecoxib compared with placebo in the treatment of stage III colon cancer and was conducted at 654 sites throughout the United States and Canada.
The study included 2524 patients in the primary analysis who were randomly assigned to receive adjuvant FOLFOX every 2 weeks for 3 or 6 months with or without 3 years of concurrent daily celecoxib (400 mg orally/d; 1263 patients) or placebo (1261 patients).
Approximately 71% of the patients treated with celecoxib and 70% of the patients treated with placebo adhered to the protocol treatment, which was defined as receiving celecoxib or placebo for more than 2.75 years or continuing treatment until recurrence, death, or unacceptable adverse events (AEs).
As stated by the investigators, the median follow-up of the surviving patients was 6 years. A total of 700 patients (337 patients in the celecoxib group and 363 patients in the placebo group) experienced disease recurrence or death.
There was no significant difference in the 3-year DFS rates for patients treated with celecoxib (76.3%) vs those treated with placebo (73.4%; hazard ratio [HR] for disease recurrence or death, 0.89; 95% CI, 0.76-1.03; P =.12). Likewise, no significant difference was observed in the 5-year OS rates between the celecoxib group (84.3%) and placebo group (81.6%; HR for death, 0.86; 95% CI, 0.72-1.04; P =.13).
During adjuvant FOLFOX treatment, 51.7% of the patients in the celecoxib group and 50.8% of the patients in the placebo group experienced grade 3 or worse AEs. Any grade hypertension was reported among 14.6% of the patients in the celecoxib group and 10.9% of patients in the placebo group during adjuvant treatment. After completion of FOLFOX treatment, 1.7% of the patients in the FOLFOX group and 0.5% of patients in the placebo group had a grade 2 or greater increase in creatinine levels.
“Although aspirin and [COX-2] inhibitors have been associated with a reduced risk of colorectal polyps and cancer in observational and randomized studies,” as stated by the study authors, the results of the present study did not support the use of celecoxib as a treatment for nonmetastatic colon cancer.
Disclosure: This research was supported in part by Pfizer. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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 III colon cancer: the CALGB/SWOG 80702 (Alliance) randomized clinical trial. JAMA. 2021;325(13):1277-1286. doi:10.1001/jama.2021.2454