UTILITY OF ADJUVANT ASPIRIN IN CRC NOW HAS BIOMARKER

A recent study points to a useful biomarker for patients with colorectal cancer who might benefit from adjuvant aspirin therapy.

Previous published studies have confirmed anecdotal observations of the benefit of aspirin therapy in improving outcomes in certain cancers. Researchers in Boston and Japan analyzed data obtained from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) to determine if the regular use of aspirin had a significant effect on survival among patients with colorectal cancer.

Xiauyun Liao, PhD, and colleagues at the Dana-Farber Cancer Institute in Boston, selected 964 patients who had been diagnosed with rectal or colon cancer, reviewing data on survival, aspirin use before and after diagnosis, and tumor tissue data, including the presence of the PIK3CA mutation, present in 15%-20% of colorectal cancers. Biomarkers also were examined, including PTGS2 (i.e., cyclooxygenase-2), phosphorylated AKT, KRAS, BRAF and microsatellite instability. Results were published in The New England Journal of Medicine (2012;367:1596-1606, PMID 23094721).

Researchers hypothesized that regular aspirin use (defined as a standard dose taken two or more times a week during most weeks) may inhibit cancer cell growth and induce apoptosis by blocking the PI3K pathway. The results showed patients with thePIK3CA mutation who took regular aspirin had an increased survival rate compared with patients with wild-type PIK3CA, regardless of whether the aspirin therapy began before or after diagnosis.

In patients with the mutated PIK3CA gene who did not use aspirin, 23 of 90 died within five years of diagnosis, whereas only two of 62 died who had used aspirin (P<0.001). These patients had significantly increased cancer-specific survival (multivariate hazard ratio [HR] for death, 0.18; 95% confidence interval [CI], 0.06-0.61; P<0.001) and superior overall survival. Regular use of aspirin after diagnosis in patients with wild-type PIK3CA was not associated with cancer-specific survival (multivariate HR, 0.96; 95% CI; 0.69-1.32; P=0.076) or overall survival.

The authors noted the exact mechanism that causes these results needs to be clarified and that the heterogeneous nature of colon cancers may also affect outcomes. They conclude that colorectal cancer patients with the PIK3CA mutation would derive a benefit from aspirin as an adjuvant therapy, and that the mutation might provide a useful biomarker for such therapy.

From The New England Journal of Medicine