Routine aspirin for cancer primary prevention ‘a step closer’
MedWire News: More evidence has emerged that daily aspirin is effective in the primary prevention of cancer, with new data also suggesting the drug helps treat existing cancers.
Having previously demonstrated that daily aspirin reduces 20-year cancer mortality, Peter Rothwell (University of Oxford, UK) and colleagues now report that the effect emerges in the short term, with a reduction in cancer incidence seen from around 3 years of follow up, and in cancer deaths from around 5 years.
Moreover, they report that an even earlier reduction in cancer mortality was seen in high-dose aspirin trials, suggesting that the drug prevented growth of clinically occult cancers present at randomization.
In the first of two studies published in the Lancet, Rothwell and team studied individual patient data from randomized trials of aspirin versus no aspirin for prevention of vascular events. Data available for 34 trials, including 69,224 participants, revealed that allocation to aspirin reduced the risk for death due to cancer by a significant 15%.
Stratification by time to death, using data from 32 of the trials, showed that this improved to a 37% reduction in risk for cancer death from 5 years onwards. Cancer deaths were also reduced during the first 3 years in trials of high-dose aspirin, by 31%.
Further analysis showed that daily low-dose aspirin reduced cancer incidence by a quarter from 3 years onwards.
The authors also found that an initial reduction in vascular deaths on aspirin and increased risk for major bleeding diminished over time, such that only the reduced cancer risk was evident from 3 years onwards (absolute reduction of three cases per 1000 patients per year). Of note, aspirin users also had two-thirds lower case-fatality from major extracranial bleeds than control participants.
The authors write: "Alongside the previously reported reduction by aspirin of the long-term risk of cancer death, the short-term reductions in cancer incidence and mortality and the decrease in risk of major extracranial bleeds with extended use, and their low case-fatality, add to the case for daily aspirin in prevention of cancer."
They also note that, given the very low rates of vascular events in recent and ongoing primary prevention trials, "prevention of cancer could become the main justification for aspirin use in this setting."
In a second study, the authors report findings from five large randomized trials of daily aspirin compared with control, which suggest that the early effects on cancer death may be partly due to a reduction in distant metastasis. The results showed that aspirin reduced the risk for cancer with distant metastasis by 36%, the risk for adenocarcinoma by 46%, and that for other solid cancers by 18%, due mainly to a reduction by half in the proportion of adenocarcinomas that had metastatic versus local disease.
A third study, published in the Lancet Oncology, looked at case-control studies and found a 38% reduction in colorectal cancer with aspirin use that was similar to the 42% reduction in risk previously reported from analysis of randomized trials. Similarly matched risk reductions were seen for esophageal, gastric, biliary, and breast cancer.
Writing in an accompanying editorial, Andrew Chan and Nancy Cook, from Harvard Medical School in Boston, Massachusetts, USA, say it is still too soon to recommend routine use of aspirin at the population level.
They say that the Women's Health Study and the Physician's Health Study, with less potential for bias given they included cancer as a prespecified endpoint, remain "significant counterbalancing trials that found no cancer benefit with alternate-day aspirin up to 10-12 years."
Furthermore, they argue that "despite a convincing case that the vascular and anticancer benefits of aspirin outweigh the harms of major extracranial bleeding, these analyses do not account for less serious adverse effects on quality of life, such as less severe bleeding."
Nonetheless, they conclude, the current evidence "moves us another step closer to broadening recommendations for aspirin use," and means that guidelines should now consider aspirin for cancer prevention as well as for prevention of vascular disease.
By Caroline Price