O-0012 - Are the benefits of aspirin in colorectal cancer limited to PIK3CA mutated cancers?

Date 27 June 2014
Event World GI 2014
Session Presentation of selected abstracts
Topics Cancer Aetiology, Epidemiology, Prevention
Colon Cancer
Rectal Cancer
Presenter R. Langley
Citation Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193
Authors R. Langley1, C. Coyle1, D. Gilbert2, S. Rowley1, C. Murphy1, L. Stevenson1, D. Cameron3, M. Parmar1, R. Wilson4
  • 1Medical Research Council Clinical Trials Unit at UCL, London/UK
  • 2Sussex Cancer Centre, Brighton/UK
  • 3Edinburgh Cancer Research Centre, Edinburgh/UK
  • 4Northern Ireland Cancer Trials Centre and Network Centre for Cancer Research and Cell Biology Queen's University Belfast, Belfast/UK



Evidence has recently emerged to suggest that mutations in the PIK3CA gene in colorectal cancer might identify patients that receive greater benefit from aspirin in the adjuvant setting. Add-Aspirin is a planned and funded, double blind, placebo-controlled, randomised trial assessing the potential benefits of aspirin after primary curative therapy for non-metastatic cancer (colorectal, gastro-oesophageal, breast and prostate cancer). Participants (n = 9920 which includes 2600 with colorectal cancer) will receive aspirin 100mg daily, aspirin 300mg daily or matching placebo for at least 5 years. Each tumour specific cohort is individually powered and has a separate co-primary outcome measure.


We assessed current data on the association between PIK3CA mutation status and benefit from aspirin after a colorectal diagnosis, as well as other genetic mutations associated with benefit from aspirin to assess how this should be addressed within the setting of a planned randomised adjuvant trial.


Long-term follow-up of randomised trials designed to assess vascular benefits of aspirin, show that taking daily low-dose aspirin for 5 years reduces the incidence of cancer, particularly those that arise from the gastrointestinal tract (1). Observational data suggest aspirin is associated with a lower risk of developing BRAF-wild type colorectal tumours (2). Recent data on the association between PIK3CA mutation status, aspirin use and survival outcomes involve small numbers of patients with mutations, and include stage I-IV patients where the biological effects may be different and are not consistent (see table1).


The potential benefits of aspirin include effects on both the development of primary tumours, as well as the development and spread of metastases which may involve different signaling pathways. To date the data suggest that patients with both mutated and wild type PIK3CA colorectal tumours may benefit from aspirin after a diagnosis of colorectal cancer. Add-Aspirin incorporates an active run-in period which can be utilised to ascertain PIK3CA mutation status in the colorectal cohort prior to randomisation and used as a stratification factor, providing a framework to investigate this important clinical question efficiently and reliably. Subgroup analyses by PIK3CA status are planned and accumulating data will be reviewed by an Independent Data Monitoring Committee ensuring the full potential benefits of aspirin are realised.


1. Rothwell, P.M., et al., Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet, 2011. 377(9759): p.31-41.

2. Nishihara, R., et al., Aspirin use and risk of colorectal cancer according to BRAF mutation status. JAMA, 2013. 309(24): p.2563-71.

3. Liao, X., et al., Aspirin Use, Tumor PIK3CA Mutation, and Colorectal-Cancer Survival. NEJM, 2012. 367(17): p.1596-1606.

4. Domingo, E., et al., Evaluation of PIK3CA Mutation As a Predictor of Benefit From Nonsteroidal Anti-Inflammatory Drug Therapy in Colorectal Cancer. J Clin Oncol, 2013. 31(34): p.4297-305.

5. Kothari, N., et al., Regular aspirin (ASA) use and survival in patients with PIK3CA-mutated metastatic colorectal cancer (CRC). J Clin Oncol, 2014. 32 (suppl3; abstr386).

6. Reimers, M.S., et al., Low dose aspirin use after diagnosis, HLA class I tumour expression and colon cancer survival. JAMA Internal Medicine (in press), 2014.