Aspirin use after radical cancer therapy – feasibility and toxicity data from the Add-Aspirin trial


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Nalinie Joharatnam1,Fay Cafferty1,Alistair Ring2,Howard Kynaston3,Richard Wilson4,Duncan Gilbert5,David Cameron6,Farhat Din6,Richard Hubner7,Anne Thomas8,Daniel Swinson9,Janusz Jankowski10,Sam Rowley11,Martin Scott-Brown12,Chris Price13,Alex Walther14,David Eaton15,Nicola Ainsworth16,Rachel Kerr17,Luke Hughes-Davies18,Max Parmar1,Conjeeveram Pramesh19,Sudeep Gupta19,Ruth Langley1
1MRC Clinical Trials Unit at UCL,2The Royal Marsden NHS Foundation Trust,3Cardiff and Vale University Health Board,4Queen's University Belfast,5Brighton and Sussex University Hospitals NHS Trust,6The University of Edinburgh,7The Christie NHS Foundation Trust,8University Hospitals of Leicester,9Leeds Teaching Hospitals NHS Trust,10University of Central Lancashire,11MRC CTU at UCL,12University Hospitals of Coventry and Warwickshire NHS Trust,13Worcestershire Acute Hospitals NHT Trust,14University Hospitals Bristol NHS Foundation Trust,15University Hospitals of Morecambe Bay NHS Foundation Trust,16The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust,17Oxford University Hospitals NHS Trust,18Cambridge University Hospitals NHS Foundation Trust,19Tata Memorial Centre

Abstract

Background

Pre-clinical, observational and randomised evidence suggests aspirin may prevent or delay the development of cancer and metastases, and is strongest for colorectal and gastro-oesophageal cancer. However, concerns around feasibility, adherence and tolerability (particularly serious bleeding) have limited aspirin use for cancer chemoprevention.

Method

Add-Aspirin is a double-blind, randomised-controlled trial encompassing 4 individually powered phase III trials in early-stage breast, prostate, colorectal and gastro-oesophageal cancer, evaluating the effect of aspirin after radical therapy. All participants initially take open-label aspirin (100mg daily) for 8 weeks (run-in), to assess adherence and toxicity prior to randomisation (1:1:1, aspirin 300mg, aspirin 100mg or matched placebo for ≥5 years). A pre-planned feasibility analysis was performed to assess tolerability and adherence when >2000 participants had completed the run-in period.

Results

Between October 2015 and October 2017, 3494 of a targeted 11000 participants were registered from 165 sites in the UK; recruitment rates differed across tumour sites compared to predictions. Run-in data (n=2253) showed good adherence: 95% took 6-7 tablets/week and 85% proceeded to randomisation, with rates consistent across tumour cohorts. Main reasons for not proceeding to randomisation were toxicity (mostly minor, grade 1/2) and/or patient choice, with only 0.7% (16/2253) of participants experiencing toxicity requiring discontinuation during the run-in. Fewer than 1% (13/2253) experienced a grade > 3 toxicity (including one lower gastrointestinal bleed in a prostate cancer participant; no upper gastrointestinal bleeds).

Conclusion

The data demonstrate that aspirin is well-tolerated over an 8-week run-in, and acceptable to patients after radical cancer therapy, with low toxicity rates in all tumour cohorts, including gastro-oesophageal participants. A run-in approach may be useful in adjuvant (or prevention) studies for reducing the risk of non-adherence and participant attrition at a later date. Trial recruitment continues with >5000 participants now registered from the UK and India.