A large randomised trial was halted after preliminary analysis found that taking aspirin after treatment for breast cancer did not reduce the risk of disease recurrence.
Laboratory studies had previously shown that aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) reduced breast cancer growth and invasion. Non-steroidal anti-inflammatory drugs (NSAIDs) display anticancer activity through the inhibition of the COX-2 enzyme, triggering processes such as apoptosis, a reduction in proliferation and inhibition of carcinogenesis. Several observational studies have shown a reduced risk of breast cancer mortality among regular aspirin users.
There was a 25% higher risk of invasive recurrence in patients who took aspirin for a median of 18 months, but not statistically different from placebo (P = 0.1258). The aspirin group had an excess of all disease-related events, including death, local and distant recurrence/progression, and new primary tumours.
The results are in line with similar trials that ended while the Aspirin after Breast Cancer (ABC) trial was ongoing, Wendy Y. Chen, MD, of Dana-Farber Cancer Institute in Boston, said during a presentation at the American Society of Clinical Oncology (ASCO) Plenary Series.
“In this double-blind, placebo-controlled randomised trial, there was no benefit of aspirin 300 milligrams daily in terms of breast cancer invasive disease-free survival,” reported Dr Chen. “Although follow-up was short, the futility bound was clearly crossed. We had reached 50% of the events, and there was a numerically higher number of events in the aspirin arm. Therefore, it was unlikely that even with further follow-up there wouldn’t be any benefit associated with aspirin.”
“Although inflammation may still play a key role in cancer, it’s important to remember that aspirin may have different effects in other cancers, such as colon, or in different settings, such as primary versus secondary prevention,” she added.
Though the trial was well designed, enrolled the right population and with adequate dosing. the trial was stopped early for futility, commented Angela DeMichele, MD, of the Abramson Cancer Center at the University of Pennsylvania.
“The direction and magnitude [of the difference in events] highly preclude the possibility that there would have been a benefit with more follow-up,” said Dr DeMichele. “Although it was not statistically significant, we cannot rule out the possibility of a potential increase in breast cancer recurrence from the use of aspirin.”
“For patients and providers at this time, aspirin should not be used simply to prevent breast cancer recurrence,” she continued. “For those situations in which there are other options, decisions about aspirin use for other indications should definitely include an individualised risk/benefit discussion between physician and patient.”
The results underscore the need for prospective, randomised clinical trials to validate the effects of interventions from observational studies, she concluded.
The ABC trial involved patients under 70 with HER2-negative, high-risk breast cancer. The study randomised 3021 participants to 300 mg of aspirin daily or matching placebo for 5 years, with the primary endpoint being invasive disease-free survival.
Dr Chen further noted that three clinical trials of aspirin or NSAID treatment ended while the ABC trial was ongoing. The Canadian-led MA.27 trial of an aromatase inhibitor plus celecoxib ended due to toxicity in the celecoxib arm. The randomised REACT trial of celecoxib in HER2-negative breast cancer showed no difference in disease-free survival after more than 6 years of follow-up.
The ASPREE trial tested low-dose aspirin on all-cause mortality in healthy older patients, and results showed a trend to increased all-cause mortality and significantly higher cancer mortality in the aspirin arm.
During the post-presentation discussion, an audience member asked whether the results definitively ruled out a late benefit of aspirin, given that most patients had HR-positive disease wherein late relapse is not uncommon.
“It’s always frustrating when a study is closed early, and it was done in this case after we had reached 50% of the expected benefits,” said Chen. “There was an increase [in clinical events]. Not a statistically significant increase, but it was bordering on statistical significance. In order for aspirin to have a benefit, it would mean that in the second half, there would need to be a significantly decreased risk. It would basically need to flip and that would be biologically difficult to imagine.”
“I think it’s fair to say that this study doesn’t say definitively that there’s harm, but as for the likelihood of a benefit of aspirin, that would be extremely unlikely,” she said.
Source: MedPage Today
