CaPPtain's Blog: John Burn, February 2020

I saw my first daffodils this week.  Spring is coming soon and with it good news. 

The first event of note is the completion of the NICE^* approval of aspirin as a preventive agent in Lynch syndrome.  This guidance became official in January, complementing the decision of the British Society of Gastroenterology to make the same recommendation and international endorsement via the formal voting system among members of the European Hereditary Tumour Group.  Aspirin is still not formally licensed for cancer prevention in the UK but we are working on that too.  Meanwhile doctors can prescribe aspirin, if they agree with this guidance. 

The NICE endorsement will, hopefully, be stronger following the imminent publication by the Lancet of our latest paper documenting the planned CAPP2 trial 10 year follow up, supplemented by registry data in England, Wales and Finland for the second decade.  The bottom line is that the effect of aspirin (600mg daily) on colorectal cancers (CRC) is even more secure, with a significant reduction with the rigorous method of Hazard Ratio on the basis of Intention to Treat. In plain English, this means that even when we count only the first colon cancer and include all the people allocated to the aspirin group, even if they dropped out early, there are significantly fewer cancers in the people in the aspirin group.  When we focus on people who actually took the two aspirins a day for two years and including all their primary colorectal cancers in the analysis, the relative risk is 0.50. That means they had half as many colorectal cancers over an average of ten years.

There were also fewer non-CRC Lynch syndrome cancers but overall, the statistical significance was lost by 10 years.  This probably means that the effect is not as long lasting and may not apply to all types of cancer.  We do, however, have new information on resistant starch, the diet supplement in CAPP2.  Those of you who follow me on twitter (@CaPP3) will have seen that I reported to the recent Clinical Genetics Society meeting in Cambridge that the non-CRC Lynch cancers were reduced in the people who were given the active diet supplement compared to the placebo group.

CaPP3 is still on course and has become even more important as NICE recognise the importance of our ongoing trial.  They endorsed our suggestion that while we await the result of CaPP3 the "best guess" is that people should take 150mg (two "cardio" aspirins) if they are below 70kg (11 stone) and 300mg (a standard aspirin) if they are over that weight.  This is based on our overall reading of the literature.  I hope people who are in CaPP3 will continue for the five years, as planned on their study dose so that we can see if the different doses do have a different effect.  The first recruit to the trial, Nick from Newcastle, has now completed his five years along will several more early participants while the last recruit will complete the 2 year "blind" phase next spring.  That means we still have four years to wait but it will be worth it.  Some experimental work by Rick Boland and colleagues in America has supported the CaPP3 plan; they simulated the three doses using cancer cells in the laboratory and saw a bigger effect with the higher doses.  On the other hand, of course, we expect more side effects with the higher doses so there will need to be a careful assessment of the pros and cons at the end of the trial.  If you are still in CaPP3, thanks again! Please keep in touch.  We are always keen to hear from you.

*NICE stands for the National Institute for Health and Care Excellence

John Burn
27th February 2020