Nalinie Joharatnam-Hogan1, Fay Cafferty1, Richard Hubner2, Daniel Swinson3, Sharmila Sothi4, Kamalnayan Gupta5, Stephen Falk6, Kinnari Patel7, Nicola Warner8, Victoria Kunene9, Sam Rowley1, Komel Khabra1, Tim Underwood10, Janusz Jankowski11, John Bridgewater12, Anne Crossley3, Verity Henson6, Lindy Berkman13, Duncan Gilbert1, Howard Kynaston14, Alistair Ring15, David Cameron16, Farhat Din16, Janet Graham17, Timothy Iveson18, Richard Adams19, Anne Thomas20, Richard Wilson21, C S Pramesh22, Ruth Langley23. 1. MRC Clinical Trials Unit, University College London, UK. 2. The Christie Hospital, Manchester, UK. 3. St James University Hospital, Leeds, UK. 4. University Hospital Coventry and Warwickshire, UK. 5. Worcestershire Royal Hospital, Worcester, UK. 6. Bristol Haematology & Oncology Centre, Bristol, UK. 7. Churchill Hospital, Oxford, UK. 8. Stoke Mandeville Hospital, Aylesbury, UK. 9. Manor Hospital, Walsall, UK. 10. University of Southampton, Southampton, UK. 11. Gastroenterology Unit, Morecambe Bay University Hospitals NHS Trust, UK; National Institute for Health and Care Excellence, London, UK. 12. University College Hospital London, UK. 13. NCRI Consumer Liaison Group, London, UK. 14. Cardiff University, Cardiff, UK. 15. Royal Marsden Hospital, London, UK. 16. Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, Western General Hospital, Edinburgh, UK. 17. Beatson West of Scotland Cancer Centre, Glasgow, UK. 18. Southampton General Hospital, UK. 19. Velindre Cancer Centre, Cardiff, UK. 20. Leicester Royal Infirmary, Leicester, UK. 21. University of Glasgow, Glasgow, UK. 22. Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India. 23. MRC Clinical Trials Unit, University College London, UK. Electronic address: ruth.langley@ucl.ac.uk.
Abstract
BACKGROUND: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer. METHODS: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survivalafter radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment. FINDINGS: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants). INTERPRETATION:Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes. FUNDING: Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.
RCT Entities:
BACKGROUND: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer. METHODS: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment. FINDINGS: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants). INTERPRETATION:Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes. FUNDING: Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.
Authors: C S Pramesh; Rajendra A Badwe; Nirmala Bhoo-Pathy; Christopher M Booth; Girish Chinnaswamy; Anna J Dare; Victor Piana de Andrade; David J Hunter; Satish Gopal; Mary Gospodarowicz; Sanjeeva Gunasekera; Andre Ilbawi; Sharon Kapambwe; Peter Kingham; Tezer Kutluk; Nirmal Lamichhane; Miriam Mutebi; Jackson Orem; Groesbeck Parham; Priya Ranganathan; Manju Sengar; Richard Sullivan; Soumya Swaminathan; Ian F Tannock; Vivek Tomar; Verna Vanderpuye; Cherian Varghese; Elisabete Weiderpass Journal: Nat Med Date: 2022-04-19 Impact factor: 87.241
Authors: Jeffrey A Meyerhardt; Qian Shi; Charles S Fuchs; Jeffrey Meyer; Donna Niedzwiecki; Tyler Zemla; Priya Kumthekar; Katherine A Guthrie; Felix Couture; Philip Kuebler; Johanna C Bendell; Pankaj Kumar; Dequincy Lewis; Benjamin Tan; Monica Bertagnolli; Axel Grothey; Howard S Hochster; Richard M Goldberg; Alan Venook; Charles Blanke; Eileen M O'Reilly; Anthony F Shields Journal: JAMA Date: 2021-04-06 Impact factor: 56.272