Patients assigned to receive high-dose eicosapentaenoic acid (EPA), an omega-3 fatty acid, before and after surgery for colorectal cancer liver metastases had longer overall survival than those assigned to receive placebo, according to results of the phase 3 trial presented at the ESMO Congress 2026.
Surgery to remove colorectal cancer that has spread to the liver offers the possibility of long-term survival, but recurrence remains common. Preclinical and observational studies have suggested that EPA may have activity against colorectal cancer, while an earlier phase 2 trial indicated a possible survival benefit.
The randomised, double-blind, placebo-controlled trial enrolled 418 patients scheduled for liver resection with curative intent at 13 UK hepatobiliary surgery centres. Patients were assigned to 4g daily of EPA, as high-purity prescription icosapent ethyl, or mineral oil placebo. Treatment began at least one day before surgery and was planned to continue for two to four years, even after cancer progression. Other cancer treatments were broadly comparable, with 20% in each group receiving adjuvant chemotherapy.
Estimated five-year overall survival, the trial’s key secondary endpoint, was 62.0% with EPA versus 45.1% with placebo. EPA was associated with a 32% lower hazard of death (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.48–0.96; p=0.03). Median overall survival had not been reached with EPA versus 59.0 months with placebo. The survival benefit was consistent in the per-protocol analysis (HR 0.60; 95% CI 0.36–0.99). It also remained consistent after adjustment for diabetes, which was more common at baseline in the EPA group (16% versus 8%), and in other sensitivity analyses. However, median progression-free survival (PFS) was similar in the two groups (13.5 versus 12.9 months; HR 0.89; 95% CI 0.70–1.13; p=0.33).
EPA was well tolerated, with no excess adverse events, bleeding or atrial fibrillation compared with placebo, and no negative impact on quality of life.
