Aspirin and Advanced Cancer: Older Adults May Be At Risk for Faster Disease Progression

According to the results of a new analysis published in the Journal of the National Cancer Institute, aspirin may speed up disease progression in older adults who have advanced stage cancer.

“The ASPirin in Reducing Events in the Elderly (ASPREE) was a randomized controlled trial (RCT) comparing daily low-dose aspirin (100mg) versus placebo in 19,114 Australian and U.S. adults aged 70 years or older (or ≥ 65 years of age among U.S. African Americans and Hispanics) who were free of known cardiovascular disease, dementia, or physical disability at trial entry. We recently reported that ASPREE participants randomized to aspirin experienced higher all-cause mortality. This became evident at three years post-randomization and was largely attributable to death from cancer,” the study authors explained.

The present analysis therefore reported a closer examination of the effects of aspirin on mortality in this patient population.

ASPREE recruited patients from Australia (n=16,703) and the U.S. (n=2,411) from March 2010 through 2014. Patients were randomized to receive either daily 100 mg of enteric coated aspirin (n=9,525) or placebo (n=9,589). Patients were required to be in good health at the start of the trial and expected to live for at least five years, although previous cancer was not an excluding factor and was reported in 19% of patients.

Aspirin and Cancer Progression, Mortality

The aspirin group reported 981 cancer events, and the placebo group had 952. The groups did not largely differ in risks for all incident cancers (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.95 to 1.14), hematological cancer (HR, 0.98; 95% CI, 0.73 to 1.30), or all solid cancers (HR, 1.05; 95% CI, 0.95 to 1.15), but aspirin was correlated with a higher risk of incident cancer that had metastasized (HR, 1.19; 95% CI, 1.00 to 1.43) or was stage 4 when diagnosed (HR, 1.22; 95% CI, 1.02 to 1.45), as well as death for cancers that presented at either stage 3 (HR, 2.11; 95% CI, 1.03 to 4.33) or stage 4 (HR, 1.31; 95% CI, 1.04 to 1.64).

“Deaths were particularly high among those on aspirin who were diagnosed with advanced solid cancers, suggesting a possible adverse effect of aspirin on the growth of cancers once they have already developed in older adults,” said senior author Andrew T. Chan, MD, MPH, chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital, director of epidemiology at the hospital’s Cancer Center, and a professor of Medicine at Harvard Medical School, in a press release.

Most of the patients involved in the study had not been previously taking aspirin, though.

“Although these results suggest that we should be cautious about starting aspirin therapy in otherwise healthy older adults, this does not mean that individuals who are already taking aspirin—particularly if they began taking it at a younger age—should stop their aspirin regimen,” Dr. Chen explained.

In an accompanying editorial, researchers wrote, “Together, these findings alter the calculus of aspirin’s risks and benefits such that its use as a cancer chemopreventive agent in the general population looks less likely. Lifestyle modifications combined with age- and risk-based screening will continue to be the mainstay for cancer prevention among the healthy, unselected general public,” noting that aspirin should only be used in patients with specific patient populations.

They continued, “Finally, the unexpected and unexplained results of ASPREE suggest that we may still be missing a critical piece of the puzzle in our understanding of aspirin’s biologic effects on cancer development and evolution within and across individuals of differing ages. Careful post-trial follow-up of the ASPREE participants is warranted, as are mechanistic studies to better understand how aspirin’s effects on cancer development could differ so profoundly by age.”