Examining the impact of regular aspirin use and PIK3CA mutations on survival in stage 2 colon cancer

Intern Med J. 2017 Jan;47(1):88-98. doi: 10.1111/imj.13312.

Abstract

Background/aim: Data suggest aspirin improves survival in colorectal cancer (CRC) harbouring PIK3CA mutations. The impact of aspirin is thought predominantly to be through an anti-inflammatory effect. The aim of this study is to explore the effect of aspirin use on survival in a real-world cohort of stage 2 colon cancer (CC) patients.

Methods: A prospective CRC database identified patients diagnosed with stage 2 CC between 2000 and 2011. PIK3CA mutation status was determined by next generation sequencing. Neutrophil-lymphocyte ratio greater than 5 at diagnosis represented systemic inflammation. Chart review was used to record regular aspirin use at diagnosis. Clinico-pathological features and survival data were available. Survival analyses used the Cox proportional hazards method.

Results: Of 488 patients with stage 2 CC, 95 patients were aspirin users and 70 patients had PIK3CA mutations. Aspirin users were more likely to be older (median: 76.4 years vs 68.3 years, P < 0.001), to be less fit (American Society of Anaesthetists Score 3-4: 58% vs 31%, P < 0.001) and to have systemic inflammation (neutrophil-lymphocyte ratio > 5: 39% vs 27%, P = 0.027). Regular aspirin use did not significantly improve recurrence-free survival. In the PIK3CA mutated group, there was a trend towards improved recurrence-free survival (hazard ratio: 0.45, P = 0.42).

Conclusions: Our study did not demonstrate a significant survival advantage from aspirin use in stage 2 PIK3CA mutated CC. The 'real-world' nature of our cohort and the subsequent uncontrolled differences in age and fitness in aspirin users are likely to have contributed to this result. Defining the true impact of aspirin in CRC requires prospective randomised clinical trials.

Keywords: PIK3CA; aspirin; colon cancer; colorectal cancer; real-world data.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / therapeutic use*
  • Australia
  • Class I Phosphatidylinositol 3-Kinases
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / mortality*
  • Colonic Neoplasms / therapy*
  • Databases, Factual
  • Female
  • Genetic Testing
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Phosphatidylinositol 3-Kinases / genetics*
  • Prospective Studies
  • Survival Analysis

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Aspirin