November 4th, 2026
Summary by Mark L. Fuerst
High-dose omega-3 eicosapentaenoic acid (EPA) reduced the risk of death by approximately 30% compared to placebo in patients with colorectal cancer liver metastases (CRLM) after resection surgery, according to results of the phase III EMT2 trial presented at the ESMO Congress 2026 (Abstract LBA30).
The estimated 5-year overall survival (OS) in the EPA arm was 62% compared to 45.1% in the placebo arm, translating to a 32% lower hazard of death.
“The overall survival benefit seen with EPA in EMT2, if confirmed in other studies, is clinically meaningful for the group of patients who have had surgery for bowel cancer spread to the liver and in whom the cancer frequently comes back,” said lead author Professor Mark Hull, Professor of Molecular Gastroenterology at the Leeds Institute of Medical Research, University of Leeds, U.K. “This is particularly the case as EPA is well-tolerated and safe, even when other cancer treatments are needed.”
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. An earlier phase II trial led by Hull had indicated a possible survival benefit. Oral administration of the omega-3 fatty acid EPA, as a free fatty acid, leads to EPA incorporation into, and reduced growth of, experimental CRLM, Hull and colleagues had previously found.
Study Details
The new multicenter, randomized, double-blind, placebo-controlled phase III EMT2 trial enrolled 418 patients scheduled for liver resection with curative intent at 13 U.K. hepatobiliary surgery centers. Adult patients undergoing CRLM resection with curative intent were randomly assigned by the use of neoadjuvant chemotherapy, presence of extrahepatic metastasis, time between randomization and surgery (less than 2 weeks, 2 or more weeks), aspirin use, and recruitment center to receive either 4 g pure EPA or mineral oil placebo capsules. They started therapy at least 1 day before surgery for a minimum of 2 years and a maximum 4 years, even if colorectal cancer progression occurred. The primary endpoint was progression-free survival (PFS). The key secondary endpoint was OS.
Survival Benefit
The survival benefit was consistent in the per-protocol analysis and also remained consistent after adjustment for diabetes, which was more common at baseline in the EPA group (16% versus 8%). However, median PFS was similar in the two groups (13.5 months with EPA, 12.9 months with placebo).
Hull suggested the survival benefit might reflect effects on the body’s response to cancer, including cachexia, which can involve weight loss, reduced appetite, and fatigue. “Longer OS but no significant improvement in PFS has also been seen in trials of cancer immunotherapy. More research is needed to work out whether EPA works by improving the body’s immune response to cancer,” said Hull.
EPA was well tolerated, with no excess adverse events, bleeding, or atrial fibrillation compared with placebo, and no negative impact on quality of life, Hull said.
Intriguing Results
Chiara Cremolini, MD, PhD, Professor of Medical Oncology at the Department of Translational Research and New Technologies in Medicine and Surgery at the University of Pisa and Santa Chiara Hospital, commented, “The results are definitely intriguing, from both a biological and a clinical point of view. The lack of concordance between PFS and OS results requires careful interpretation.” She noted that PFS is a less established indicator of OS after surgery for liver metastases than after surgery for early-stage bowel cancer. Additional data would help, including the treatments patients received after their cancer returned and the pattern of spread at the time of progression.
“Confirmatory results are likely needed before incorporating this treatment option into daily clinical practice,” said Cremolini, noting that patients having surgery for liver metastases vary widely in the biological and molecular characteristics of their cancer and in their previous treatment, which future trials could take into account. “Acknowledging the difficulty of conducting clinical trials, and especially academic research, in this setting, the authors should be highly congratulated for their successful effort,” she said.