Daily aspirin was associated with reduced colorectal cancer recurrence in patients with genetic mutations
Among patients with alterations in PI3K pathway genes and a history of colorectal cancer, the estimated three-year cumulative recurrence rate was 7.7% in those who took daily low-dose aspirin compared with 14.1% in controls, a Scandinavian trial found.
Low-dose daily aspirin led to a significantly lower incidence of colorectal cancer recurrence among patients with PIK3CA hotspot mutations in exon 9 or 20 compared with placebo, according to results of a randomized controlled trial.
Patients from 33 hospitals in Sweden, Norway, Denmark, and Finland with stage I, II, or III rectal cancer or stage II or III colon cancer and somatic alterations in PI3K pathway genes were randomized to receive 160 mg of aspirin or placebo once daily for three years. Of 2,980 patients with complete genomic data available, 1,103 (37%) had alterations in PI3K pathway genes. A total of 515 patients had group A alterations, and 588 patients had group B alterations; of these, 157 and 156 received aspirin, respectively. Colorectal cancer recurrence in patients with group A alterations was the primary end point, and recurrence in group B patients, disease-free survival, and safety were secondary end points. Findings were published by the New England Journal of Medicine on Sept. 17.
In patients with group A alterations, the estimated three-year cumulative incidence of recurrence was 7.7% with aspirin and 14.1% with placebo (hazard ratio [HR], 0.49 [95% CI, 0.24 to 0.98]; P=0.04). Among those with group B alterations, the cumulative incidence of recurrence was 7.7% and 16.8%, respectively (HR, 0.42; 95% CI, 0.21 to 0.83). The estimated three-year disease-free survival rate was 88.5% with aspirin and 81.4% with placebo (HR, 0.61; 95% CI, 0.34 to 1.08) in patients with group A alterations and 89.1% with aspirin and 78.7% with placebo (HR, 0.51; 95% CI, 0.29 to 0.88) in those with group B alterations.
In the whole cohort, the estimated three-year cumulative incidence of recurrence was 4.9% with aspirin and 17.6% with placebo among women (HR, 0.25; 95% CI, 0.11 to 0.54) and 10.7% and 13.2% (HR, 0.75; 95% CI, 0.39 to 1.44), respectively, among men. The estimated number needed to treat to prevent one recurrence ranged from six among patients with pTNM stage III rectal cancer to 42 among those with pTNM stage II colon cancer. Severe adverse events occurred in 16.8% of patients taking aspirin and 11.6% of those taking placebo, most commonly postoperative complications, deep venous thrombosis, embolism, and infection.
Limitations include that the trial did not assess alternative doses or treatment durations of aspirin and was not powered to fully characterize subgroup effects.
“Taken together with previous observational, genomic, and early trial data, our findings support the integration of aspirin into clinical practice for a molecularly defined subgroup of patients with colorectal cancer,” the study authors concluded.
An accompanying editorial noted that these results, along with findings from other trials, “establish a new standard of care in which testing for mutations in PIK3CA and related genes is conducted soon after diagnosis and inexpensive, risk-adapted aspirin therapy is prescribed soon after surgery in patients whose tumors have the relevant mutations.”