A1 Journal article (refereed)
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 (2020)

Burn, J., Sheth, H., Elliott, F., Reed, L., Macrae, F., Mecklin, J.-P., Möslein, G., McRonald, F. E., Bertario, L., Evans, D. G., Gerdes, A.-M., Ho, J. W. C., Lindblom, A., Morrison, P. J., Rashbass, J., Ramesar, R., Seppälä, T., Thomas, H. J. W., Pylvänäinen, K., . . . Bishop, D. T. (2020). 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. The Lancet, 395(10240), 1855-1863. https://doi.org/10.1016/S0140-6736(20)30366-4

JYU authors or editors

Publication details

All authors or editors: Burn, John; Sheth, Harsh; Elliott, Faye; Reed, Lynn; Macrae, Finlay; Mecklin, Jukka-Pekka; Möslein, Gabriela; McRonald, Fiona E.; Bertario, Lucio; Evans, D. Gareth; et al.

Journal or series: The Lancet

ISSN: 0140-6736

eISSN: 1474-547X

Publication year: 2020

Volume: 395

Issue number: 10240

Pages range: 1855-1863

Publisher: Elsevier

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1016/S0140-6736(20)30366-4

Publication open access: Openly available

Publication channel open access: Partially open access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/70030

Publication is parallel published: http://eprints.whiterose.ac.uk/157061/

Additional information: On behalf of the CAPP2 Investigators.


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.

Keywords: cancerous diseases; bowel cancer; Lynch syndrome; pre-emption; acetylsalicylic acid

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2020

JUFO rating: 3

Last updated on 2022-17-06 at 11:54