CaPPtain's Blog: John Burn, June 2020
posted on Tuesday, 16th June 2020
Not tagged.
Well, we finally got there. The 10-year follow up paper on
the CAPP2 study is now published in the
Lancet (13th June 2020)*. It may seem a long
time since the
2011 CAPP2 paper but we wanted to extend the analysis to
include the second decade for those who started earliest. Our aim
was to see if the protective effect seen in our 2011 analysis
persisted for more than the average of 5 years since starting in
the trial.
The important take home message is that the effect was even
clearer than in 2011, the protective effect of aspirin against
colorectal cancer has persisted in this long-term follow up, for up
to 20 years. The gold standard test in any randomised trial
is to demonstrate a significant difference on "Intention to
Treat". This means that everyone who started in the aspirin
part of the trial is included, whether or not they stuck with the
treatment. This is a very hard test and the result did not
reach the necessary levels of statistical significance last time in
2011, but this time it did, providing convincing evidence that the
effect is due to an overall cancer preventative property of
aspirin.
When asking how big the difference was, known as "efficacy", it
still is sensible to look at all the cancers in the LS folk who
took the treatment for the planned two years at least. We
judged this as people who had taken a total of 1400 trial tablets
over that time period. The statistical analysis of this group
showed there were half as many colon cancers in those who took
aspirin regularly during the trial. Obviously, many may have
taken aspirin in the subsequent years after completing the CAPP2
trial but this might apply to all the participants. The only
difference between the two groups was the couple of years on the
trial when one group had real aspirin tablets and the other had
placebo tablets.
For those of you who like the real numbers, here they are:
427 people took aspirin and 40 of them got colon cancer. Two
of them got colon cancer twice, so there were 42 bowel cancers over
an average of 10 years follow up. 434 people were in the
placebo group and 58 of them got colon cancer, some more than once
making a total of 71 bowel cancers, that's 29 more than the aspirin
group.
The
UK National Institute for Healthcare and Clinical Excellence
(NICE) announced in January 2020, based on the evidence from
the 2011 CAPP2 paper, that aspirin should be recommended to all
adults with Lynch syndrome. NICE noted that the CaPP3 study
would provide information on the optimal dose but in the meantime
supported a lower dose. We are recommending 150mg daily for
people of average size, less if you are of small build and more if
you are heavier. This is based on the
recent work of Peter Rothwell reanalysing the old trial data
and,
on our paper, looking at the higher cancer risk in LS people
who were overweight. The Australian authorities have
now endorsed use of aspirin in LS and our European survey organised
by the European Hereditary Tumour Group has just been accepted for
publication and shows general professional support. It is
still a recommendation and we need to get cancer prevention listed
for aspirin in the British National Formulary.
The other big news is, of course, theCovid-19 pandemic. We
are aware that some participants in CaPP3 stopped their aspirin
after newspaper reports that non-steroidal anti-inflammatory drugs
might make the illness worse. We now know this is not
true. In fact, a couple of Covid-19 trials have now started
including aspirin as a treatment because it has been shown that
excessive clotting is part of the illness. We are planning an
aspirin trial in early Covid-19 cases in Newcastle too. The
take home message is thatIT'S OK TO TAKE ASPIRIN! People in
CaPP3 can return to their prescribed aspirin. As follow up
appointments are arranged, we will need to know who stopped taking
their aspirin and for how long, so we can include this in the final
CaPP3 analysis in 2024.
If you have Lynch syndrome and are not on the trial, then this
blog and the CAPP2 Lancet paper will support discussions with your
doctor to discuss regularly taking aspirin. Make sure your
blood pressure is normal and that you don't have a treatable
Helicobacter pylori infection in your stomach, as many people still
do. If clear, then take some aspirin to reduce your colon
cancer risk.
Thanks again to all the people who are taking part in CaPP3. And
a special thank you to the CaPP3 participants who have completed
the five years of study aspirin. You will be receiving a personal
thank you letter from the study (once approved by the ethics
committee). The CaPP3 study will keep in contact with you annually
after your Year 5 contact. As we have shown in CAPP2, your
participation in these trials is essential if we are to change
clinical practice. We still need to know the best dose, so if you
are in CaPP3, please keep taking the study aspirin.
John Burn
16th June 2020
*Additional links
https://www.ncl.ac.uk/press/articles/latest/2020/06/10yearaspirinstudy/
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30973-9/fulltext#.XuOQnsE_khU.twitter