From the Journals

Aspirin, omega-3 PUFA fail to reduce adenoma detection rate in high-risk patients

View on the News

Long road to a paradigm shift

The authors of this study suggest that daily aspirin or eicosapentaenoic acid (EPA) could lead to meaningful clinical benefit, as reflected by reductions in mean number of adenomas per participant, Evelien Dekker, MD, and Michal F. Kaminski, MD, PhD, noted in a commentary.

However, neither drug had a significant effect on the study’s primary endpoint and the effect of reducing the mean number of adenomas per participant is unknown in terms of reducing colorectal cancer risk, Dr. Dekker and Dr. Kaminski wrote. “Both measures are surrogates of colorectal cancer incidence and mortality, which should be considered ultimate endpoints for chemoprevention trials.”

Even if aspirin or EPA clearly reduced risk of colorectal cancer in high-risk patients, it’s “questionable” whether patients would be willing to take daily medication to prevent a cancer or precursor lesion at some point in the far future, they wrote, pointing to the low inclusion rate of the study, which amounted to three patients per center per year.

“Compliance to taking the medications daily in the long run might be relatively low,” Dr. Dekker and Dr. Kaminski wrote, noting a high rate of gastrointestinal adverse events in patients randomized to EPA. Moreover, analysis would need to be conducted to determine whether daily aspirin or EPA is more cost-effective than regular surveillance colonoscopy would need to be evaluated.

“The road to a paradigm shift to taking chemoprevention medications instead of, or alongside, surveillance colonoscopies is still long,” they concluded.

The commentary by Dr. Dekker and Dr. Kaminski appears in the Lancet. Dr. Dekker is with the department of gastroenterology and hepatology at Amsterdam University Medical Centres. Dr. Kaminski is with the department of gastroenterological oncology and department of cancer prevention at the Maria Sklodowska-Curie Institute–Oncology Center, Warsaw. The authors reported disclosures related to Olympus, FujiFilm, Tillots, AlfaSigma, and Norgine.


 

FROM THE LANCET

Taking aspirin or an omega-3 polyunsaturated fatty acid daily did not reduce the colorectal adenoma detection rate among high-risk patients in a randomized, placebo-controlled trial, though both drugs showed potential chemopreventive effects.

There was no evidence that aspirin, eicosapentaenoic acid (EPA), or the two agents combined had any effect on the adenoma detection rate, reported Mark A. Hull, PhD, of the Institute of Biomedical and Clinical Sciences at the University of Leeds (England), and his coinvestigators.

However, both agents decreased the mean number of adenomas per participants, and showed subtype- and location-specific reductions in adenomas that were consistent with previous studies, according to the investigators.

“Existing data on colorectal cancer risk reduction by aspirin suggest that the decrease in colorectal adenoma recurrence that we report for both agents is likely to translate into a clinically meaningful decrease in long-term colorectal cancer risk,” Dr. Hull and his coauthors said in the report, which appears in the Lancet.

Their randomized, double-blind, multicenter trial, known as the seAFOod Polyp Prevention trial, included participants aged 55-73 years with high-risk adenoma features at screening colonoscopy. A total of 709 participants were enrolled between November 2011 and June 2016.

Adenoma detection rate, the primary endpoint, was 62% overall, and similarly, 63% in the EPA group, 61% in the aspirin group, 61% in the EPA plus aspirin group, and 61% for placebo. There was no evidence that either drug had any effect on this endpoint, according to investigators, who reported risk ratios of 0.98 (95% confidence interval, 0.87-1.12) for EPA and 0.99 (95% CI, 0.87-1.12) for aspirin.

However, aspirin reduced the mean total number of adenomas per participant versus placebo (incidence rate ratio, 0.78; 95% CI, 0.68-0.90), as well as the number of adenomas in the right colon (IRR, 0.73; 95% CI, 0.61-0.88).

While EPA by contrast did not conclusively reduce the mean total number of adenomas per participant, it did reduce the number of adenomas in the left colon, with an IRR of 0.75 (95% CI, 0.60-0.94).

Both aspirin and EPA were generally well tolerated, according to Dr. Hall and his colleagues, though the number of gastrointestinal adverse events was higher in the EPA-alone group, at 146 events, versus 85, 86, and 68 events in the placebo, aspirin, and EPA plus aspirin groups, respectively.

To optimize use of aspirin and EPA for prevention of colorectal adenomas, the approach might need to be tailored to the individual patient, Dr. Hall and his coauthors wrote.

“A key objective of future work will be to apply precision medicine principles to establish which individuals might gain most from chemoprevention with one or both agents, based on baseline colorectal adenoma characteristics alone or together with other mucosal biomarkers,” they added.

Trial funding came from the U.K. Medical Research Council and the National Institute for Health Research. Medicine and placebo were provided without charge by SLA Pharma and Bayer. Dr. Hull provided disclosures related to SLA Pharma, Bayer, and Thetis Pharmaceuticals.

SOURCE: Hull MA et al. Lancet. 2018 Nov 19. doi: 10.1016/S0140-6736(18)31775-6.

Recommended Reading

Growths on scalp
MDedge Family Medicine
Growing lesion on lip
MDedge Family Medicine
Wart on scalp
MDedge Family Medicine
Growth on right hand
MDedge Family Medicine
Be judicious with empiric antibiotics for febrile neutropenia
MDedge Family Medicine
Phase 3 data support apixaban for cancer-associated VTE
MDedge Family Medicine
Telemedicine not widely used
MDedge Family Medicine
QOL is poorer for young women after mastectomy than BCS
MDedge Family Medicine
Survivors of childhood Hodgkin lymphoma face 14-fold risk of second cancers
MDedge Family Medicine
“The Physical Activity Guidelines for Americans”— a summary with tips
MDedge Family Medicine