Summary: A high-dose omega-3 supplement extended overall survival by roughly 30% in patients undergoing surgery for colorectal cancer liver metastases, despite having no significant effect on disease progression, a phase 3 trial presented at the European Society for Medical Oncology Annual Meeting 2026 found.
How did the EMT2 trial test high-dose EPA in patients?
Researchers evaluated purified eicosapentaenoic acid ethyl ester, commonly known as Vascepa, in a multicenter, double-blind phase 3 trial. Mark A. Hull, MD, of the University of Leeds, and his colleagues enrolled 418 patients with a median age of 64 years across 13 UK centers between 2018 and 2023.
Participants were randomized in a 1:1 ratio to receive either 4 grams daily of the supplement or matching mineral oil capsules as a placebo. Treatment began at least one day before surgery with curative intent for colorectal cancer liver metastases and continued for a minimum of two years and a maximum of four years, even after cancer progression.
What were the survival and progression outcomes in the study?
Patients randomized to the EPA group experienced a roughly 30% improvement in overall survival compared with the placebo group. The estimated 5-year overall survival reached 62% with the supplement versus 45.1% with the placebo, yielding a hazard ratio of 0.68.
Median overall survival stood at 59 months in the placebo arm but had not yet been reached in the EPA group. However, the supplement showed no impact on disease progression. Median progression-free survival was 13.5 months for the EPA group and 12.9 months for the placebo arm, with estimated 5-year progression-free survival rates of 23.6% and 24.5%, respectively.
Why did EPA extend survival without stopping progression?
The discordance between disease progression and overall survival remains unexplained. Hull proposed several possibilities, including anti-cachexia effects, enhanced antitumor immunity mediated by cyclooxygenase-inhibiting activity, and positive changes in the gut microbiome.
Hull noted precedent for the finding, pointing out that certain cancer immunotherapy trials have similarly shown improved overall survival without a significant impact on progression-free survival. This parallel raises the possibility that EPA may improve the body’s immune response to cancer cells.
How did experts react to the ESMO presentation?
Specialists at the European Society for Medical Oncology Annual Meeting 2026 in Madrid called the findings intriguing but urged caution. Jeffrey Meyerhardt, MD, MPH, of the Dana-Farber Cancer Institute in Boston, stated that the data should not change clinical recommendations next week.
Meyerhardt pointed to a prior small, randomized trial testing perioperative omega-3 supplements in colorectal cancer surgery that found numerically worse long-term survival in the supplement arm. Chiara Cremolini, MD, PhD, an associate professor of medical oncology at the University of Pisa, echoed the need for confirmatory results before incorporating the regimen into daily clinical practice.
What safety and compliance challenges occurred during the trial?
High-dose EPA caused no excess adverse events, bleeding, or atrial fibrillation compared with the placebo, and it showed no negative impact on overall quality of life. Treatment discontinuation was common, with only about 40% of participants in either arm completing the full treatment course.
A total of 22% of participants withdrew from the trial entirely. Hull noted that these withdrawals were balanced between study arms and typically stemmed from perceived treatment futility after cancer progression or transitions to end-of-life care rather than side effects or intolerance.
Details of the EMT2 trial endpoints and funding
What was the primary endpoint of the EMT2 trial?
The trial’s primary endpoint was progression-free survival, which showed no statistically significant difference between the EPA and placebo arms.
Who funded the phase 3 study?
The EMT2 trial was funded by Yorkshire Cancer Research, while Amarin provided the EPA and placebo capsules.
What specific supplement was administered to patients?
Participants received 4 grams daily of purified EPA ethyl ester, known commercially as icosapent ethyl or Vascepa.
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