Aspirin trialled for breast cancer recurrence prevention

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Published: 20 Dec 2013
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Dr Alistair Ring - Brighton and Sussex Medical School, UK

Dr Ring talks to ecancertv at SABCS 2013 about the 'Add-aspirin trial'.

This is a phase III double-blind placebo-controlled randomized trial assessing the addition of aspirin after standard primary therapy in breast cancer and other early stage common solid tumours.

The primary outcome will be disease-free survival. Secondary endpoints include overall survival, toxicity, cardiac morbidity and assessment of overall healthcare benefits.

Translational work will investigate mechanisms of action and biomarkers for toxicity and treatment efficacy (including PIK3CA mutation status and COX-2 expression).

Approximately 3100 patients will be needed to test for a 4% improvement in disease free survival associated with aspirin use.

‘Add Aspirin’ is a trial that it’s in evolution, it’s due to start at the beginning of 2014. What this is, it builds on years of actually preclinical data suggesting that a drug that has been around for over a hundred years, aspirin, may actually have some anti-cancer effects. If you look back thirty years in the literature there are animal studies in preclinical data suggesting that aspirin has anti-cancer activity, at least in xenograft animal models and in laboratory studies, by a number of mechanisms. More recently it has been shown in patients taking aspirin within cardiovascular and cerebrovascular prevention trials that aspirin may be able to prevent getting cancer in the first place. It has been shown in epidemiological studies in patients taking aspirin for cardiovascular and cerebrovascular reasons that aspirin may prevent getting cancer, a primary cancer, in the first place and if one looks back through the Nurses’ Health Study, which evaluated aspirin use in women who previously had been diagnosed with an early breast cancer, it was found that women who reported taking aspirin following a diagnosis of breast cancer had a lower risk of breast cancer recurrence. Now clearly there are a lot of potential reasons for that and there have been confounding variables, different reasons that women were taking the aspirin, nonetheless it is intriguing the size of the effect because it appeared that aspirin may reduce the risk of breast cancer occurrence and breast cancer death by up to a half, depending on how often you were taking the drug.

So ‘Add Aspirin’ is a series of, in fact, four parallel trials in four tumour sites including breast cancer and what that trial will do is it will take women with early stage breast cancer who have undergone their initial surgery and primary treatments and it will randomise those women to either receive a placebo or aspirin at one of two doses. We will follow up those women for breast cancer outcomes, toxicity and non-breast cancer toxicities as well. That’s a study due to start at the beginning of 2014 that will enrol over 3,000 women in the UK and India.

How does someone interested in this trial become enrolled, and do the benefits outweigh the side effects?

At this stage the contact will be through their local oncologists and the trial is being run by the MRC Clinical Trials Unit. Aspirin, of course, is a drug with side effects and that is probably what has limited its use in the primary prevention setting because if you take a large population of people and you give them aspirin you probably will reduce their risk of getting a number of different cancers but the absolute benefit of that weighed against the potential side effects, including gastrointestinal haemorrhage, may not be justified. That’s why we’re testing this drug in people who have a higher risk of cancer, in other words people who have had an early cancer before, so the absolute benefits might be larger. Clearly we’ll have to closely monitor for toxicity as one would in any trials of this kind and the sort of toxicities we’ll be looking particularly at will be gastrointestinal haemorrhage. But, interestingly, if you look at the doses that we’re using of aspirin in this study, 100mg or 300mg, the absolute risks of that toxicity are probably very low when one looks properly through the literature.

What about women who have a genetically high risk of developing breast cancer?

We know very little about women who are genetically at higher risk of cancer and what the benefits of aspirin may be but we do know quite a lot about patients who are at high risk of colorectal cancer and the benefits of aspirin. There are some very important studies, the CAPP studies, which took people at high genetic risk of developing colorectal cancer and randomised those patients to aspirin or placebo and showed in those patients taking aspirin over a long period of time reduced the risk of developing a primary colorectal cancer. So there’s certainly evidence in the high genetic risk colorectal cancer group that aspirin may reduce the risk of a primary cancer; there is not, at present, the same data for women at high genetic risk of breast cancer.