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
Year of publication
2020
Authors
Burn, John; Sheth, Harsh; Elliott, Faye; Reed, Lynn; Macrae, Finlay; Mecklin, Jukka-Pekka; Möslein, Gabriela; McRonald, Fiona E.; Bertario, Lucio; Evans, D. Gareth; Gerdes, Anne-Marie; Ho, Judy W. C.; Lindblom, Annika; Morrison, Patrick J.; Rashbass, Jem; Ramesar, Raj; Seppälä, Toni; Thomas, Huw J. W.; Pylvänäinen, Kirsi; Borthwick, Gillian M.; Mathers, John C.; Bishop, D. Timothy
Show moreAbstract
Background: Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population. Methods: In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [<1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment with English, Finnish, and Welsh participants being monitored for up to 20 years. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. The trial is registered with the ISRCTN registry, number ISRCTN59521990. Findings: Between January, 1999, and March, 2005, 937 eligible patients with Lynch syndrome, mean age 45 years, commenced treatment, of whom 861 agreed to be randomly assigned to the aspirin group or placebo; 427 (50%) participants received aspirin and 434 (50%) placebo. Participants were followed for a mean of 10 years approximating 8500 person-years. 40 (9%) of 427 participants who received aspirin developed colorectal cancer compared with 58 (13%) of 434 who received placebo. 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. Negative binomial regression to account for multiple primary events gave an incidence rate ratio of 0·58 (0·39–0·87; p=0·0085). Per-protocol analyses restricted to 509 who achieved 2 years' intervention gave an HR of 0·56 (0·34–0·91; p=0·019) and an incidence rate ratio of 0·50 (0·31–0·82; p=0·0057). Non-colorectal Lynch syndrome cancers were reported in 36 participants who received aspirin and 36 participants who received placebo. Intention-to-treat and per-protocol analyses showed no effect. 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. Interpretation: The case for prevention of colorectal cancer with aspirin in Lynch syndrome is supported by our results.
Show moreOrganizations and authors
University of Helsinki
Seppälä Toni T.
University of Jyväskylä
Mecklin Jukka-Pekka
Helsinki University Hospital Catchment Area
Seppälä Toni T.
Publication type
Publication format
Article
Parent publication type
Journal
Article type
Original article
Audience
ScientificPeer-reviewed
Peer-ReviewedMINEDU's publication type classification code
A1 Journal article (refereed), original researchPublication channel information
Journal
Parent publication name
Volume
395
Issue
10240
Pages
1855-1863
ISSN
Publication forum
Publication forum level
3
Open access
Open access in the publisher’s service
Yes
Open access of publication channel
Partially open publication channel
License of the publisher’s version
CC BY
Self-archived
Yes
License of the self-archived publication
CC BY
Other information
Fields of science
Cancers; Surgery, anesthesiology, intensive care, radiology; Public health care science, environmental and occupational health
Keywords
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Publication country
United Kingdom
Internationality of the publisher
International
Language
English
International co-publication
Yes
Co-publication with a company
No
DOI
10.1016/S0140-6736(20)30366-4
The publication is included in the Ministry of Education and Culture’s Publication data collection
Yes