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CAPP2 trial: Aspirin reduced the rate of bowel cancer by half for patients with Lynch syndrome

Mon, 06/15/2020 - 15:13
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A regular dose of aspirin to reduce the risk of inherited bowel cancer lasts at least ten years after stopping treatment, according to the results from the ‘Cancer prevention with aspirin in hereditary colorectal cancer international trial (CAPP2)’ international trial. The research involved patients with Lynch syndrome from around the world and revealed that two aspirins a day, for an average of two and a half years, reduced the rate of bowel cancer by half.

The study, ‘Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial’, published in The Lancet and led by experts at the Universities of Newcastle and Leeds, UK, is a planned double blind ten year follow-up, supplemented in more than half of recruits with comprehensive national cancer registry data for up to 20 years.

The findings of the study further strengthens the UK’s National Institute for Health and Care Excellence (NICE) recommendation on taking daily aspirin for those at high risk and supports wider use of aspirin to prevent cancer.

Based on the preliminary five-year data from the CAPP2 trial, NICE recommended that aspirin should be offered for the prevention of bowel cancer in adults with Lynch syndrome.

"I had an idea 30 years ago that people with a genetic predisposition to colon cancer could help us to test whether aspirin really could reduce the risk of cancer,” said Professor Sir John Burn, from Newcastle University and Newcastle Hospitals NHS Foundation Trust, who led the research. "Patients with Lynch syndrome are high risk and this offered statistical power to use cancer as an endpoint, they are like the canaries in the mine who warned the miners that there was gas. It took a long time to start the trial and to recruit enough people in 16 countries, but this study has finally given us an answer.

Findings showed that when all original recruits were included in the study, those on aspirin had 42% fewer colon cancers. Among those who took the aspirin for a full two years, there were 50% fewer colon cancers.

The study involved 861 patients from 43 international centres worldwide (707 from Europe, 112 from Australasia, 38 from Africa, and four from The Americas) with Lynch syndrome, which affects about one in 200 people in the population. These people have a genetic problem with DNA repair, making them at much higher risk of cancers such as bowel and womb.

A group of 427 were randomised to aspirin continuously for two years and 434 were allocated to a placebo and then they were all followed for ten years. Out of those given two aspirins each day (600mg) there were 18 fewer colon cancers, representing a drop of 42.6%.

When all 163 Lynch syndrome cancers are included in the analysis - such as cancer of the endometrium or womb— - here was an overall reduced risk of cancer of 24% in those taking aspirin, or 37% in those who took aspirin for the full two years.

Between 1999 and 2005 participants began either taking two aspirins every day for two years or a placebo. At the end of the treatment stage in 2007 there was no overall difference between those who had taken aspirin and those who had not. However, the research team anticipated a longer term effect and designed the study for continued follow-up.

By 2010 there had been 19 new bowel cancers among those who had received aspirin and 34 among those on placebo. The incidence of cancer among the group who had taken aspirin had halved and the effect began to be seen five years after patients started taking the aspirin.

Intention-to-treat Cox proportional hazards analysis revealed a significantly reduced hazard ratio (HR) of 0·65 (95% CI 0·43–0·97; p=0·035) for aspirin versus placebo.

For all Lynch syndrome cancers combined, the intention-to-treat analysis did not reach significance but per-protocol analysis showed significantly reduced overall risk for the aspirin group (HR=0·63, 0·43–0·92; p=0·018). Adverse events during the intervention phase between aspirin and placebo groups were similar, and no significant difference in compliance between intervention groups was observed for participants with complete intervention phase data; details reported previously.

"Aspirin has a major preventative effect on cancer but this doesn't become apparent until at least four years later. With the help of these dedicated volunteers we have learned something of value to us all. Before anyone begins to take aspirin on a regular basis they should consult their doctor first as aspirin is known to bring with it a risk of stomach complaints, including ulcers and bleeding,” he cautioned. "However, if there is a strong family history of cancer then people may want to weigh up the cost and health benefits of taking aspirin for at least two years."

“In conclusion, the data reported here support the recommendation that adult carriers of a pathogenic mismatch repair gene defect (Lynch syndrome) should be advised that taking 600 mg aspirin daily for at least two years significantly reduces the risk of a future cancer, bearing in mind that this effect does not become apparent for at least four years,” the international team of researchers concluded.

"Two aspirins a day for a couple of years gives protection that lasts more than ten years and the statistical analysis has become much stronger with time,” he added “For people at high cancer risk, the benefits are clear - aspirin works. Our new international trial, CaPP3, will see if smaller doses work just as well."

The team are now leading a new international trial, CaPP3, with more than 1,800 people with Lynch syndrome enrolled to look at whether smaller, safer doses of aspirin can be used to help reduce the cancer risk.