Statins may play a vital role in preventing deaths from cancer, according to two recent observational studies. One found higher survival rates for breast, ovarian and bone cancer in women; the other found higher survival rates for prostate cancer in men. So how soon are we likely to see statin-based therapies for cancer? We explore the possibilities.
At this year’s American Society for Clinical Oncology conference in Chicago, two disparate studies were presented which – despite exploring different cancers, and originating from different research teams – showed remarkably similar results.
The first study, by researchers at the Stanford University School of Medicine, looked back at data from the 15-year Women’s Health Initiative (WHI), which involved 146,000 post-menopausal women in the United States. The team examined the links between using statins, normally taken to protect against heart disease, and mortality rates from several common cancers.
The second, from the Rutgers Cancer Institute in New Jersey, examined the case notes for men with high-risk prostate cancer, to see whether statins had any effect on their outcomes.
Both papers suggested a positive role for statins, with significantly lower mortality rates among those who had been taking the cholesterol drug. In the WHI study, statins increased survival from breast, bowel and ovarian cancer by 40%. In the Rutgers study, meanwhile, prostate cancer mortality dipped by 43%.
In the days following the conference, a number of media sources jumped on these findings. The Daily Mail ran with the headline: ‘Statins slash risk of death from cancer: They slow tumour growth by up to 50% reveal major studies’, before going on to claim that ‘GPs should make patients aware of pills’ new benefits’.
Other sources, however, were quick to counsel caution, pointing out that since these were observational studies – rather than the randomised controlled trials considered the ‘gold standard’ in medicine – the findings only represent a starting point.
“More research is needed before we can say whether it would be beneficial for more women to take statins,” said Dr Richard Roope, a GP expert for Cancer Research UK, speaking of the WHI trial.
So how much weight should we place on these results, and are we likely to see statins used as a form of cancer treatment any time soon?
Combination therapy
Dr Grace Lu-Yao, who led the Rutgers University team, feels this is a critical line of research that merits further exploration.
“People can suffer greatly from the toxicity of prostate cancer treatment, so it’s impossible to understand potential therapies that can reduce its toxicity – that’s one motive behind looking into alternatives to traditional chemotherapy,” she says. “Our study was trying to identify potential cancer therapies that could control cancer progression, and identify who’s likely to benefit from an intervention.”
Her subjects were selected by evaluating Medicare data, to find patients suffering from high-risk prostate cancer between 2007 and 2009. In total, 22,110 men were studied, 1,365 of whom had died from prostate cancer by the cut-off date.
She then sought out information about their prescription drug use: 4,481 had used statins alone, 1,356 had taken statins together with metformin, and 471 had used just metformin. While patients who took metformin alone showed no survival benefits, patients who took statins alone were significantly less likely to die during the time period.
Her findings regarding the combination therapy were particularly interesting. While these patients tended to suffer more comorbidities, they showed greater survival rates than those taking metformin alone.
These benefits seemed particularly pronounced in patients with obesity and metabolic syndrome, which ties in well with earlier findings. While obese patients in general are more likely to die from prostate cancer, they are also more likely to be taking prescription drugs for unrelated conditions, which may have an inadvertent effect on the rate at which their cancer spreads.
“There was a study published last year, which showed statins and metformin together have stronger impact on reducing metastasis than traditional chemotherapy,” Lu-Yao says.
A different study, published in May 2015 in JAMA Oncology, found that among 926 men undergoing hormone therapy for advanced prostate cancer, those taking statins could expect to remain healthier for longer: on average, their condition remained stable for an additional 10 months. The lead author, Dr Philip Kantoff, explained that statins appear to keep testosterone from entering cancer cells, making hormone therapy more effective.
Correlation or causation?
The other study presented at ASCO took a retrospective look at various female cancer deaths. It found that statin use was associated with a 40% reduction in breast cancer, a 42% reduction in ovarian cancer and a remarkable 55% reduction in bone and connective tissue cancers, although conversely the risk of lung cancer appeared to be slightly raised.
“Our study found that lipid-lowering medications, including statins, are associated with lower all-cause cancer mortality, and that might be related to the lower cholesterol levels induced by those medications,” said lead researcher Dr Ange Wang on a statement. “Our findings are promising in suggesting a potential intervention that may benefit cancer patients.”
While no causal relationship has been established, and there may be other variables at stake, Wang’s findings do seem to corroborate the need for further studies on the effects of statin use on cancer. Ideally these would be randomised controlled trials as opposed to observational analyses.
The next steps
For Lu-Yao, the next step would be to conduct epidemiological studies on a large cohort of patients. The idea would be to identify the group that’s most likely to benefit from statin intervention, or a combination of metformin and statins, as well as homing in on the optimal dosage. Once a hypothesis is generated, it would be followed up by a clinical trial.
“I’m working with some physicians to design a trial to study the mechanistic pathway of statins, and I’m working to get more detailed clinical data, to try to identify what sort of population is most likely to benefit,” she says.
She raises the intriguing suggestion that, while metformin use is typically associated with increased cancer survival rates, this may in fact be due to concurrent statin use.
“The majority of patients taking metformin actually are usually using statins as well, so it’s important to point out the benefits of metformin use could be largely attributed to statins,” she says. “There’s been a media push to have larger clinical trials to test metformin alone, but my theory is we probably should wait till we have more data, as maybe statins are the key player.”
While the evidence base remains inconclusive to date – and suggestions that cancer patients should take statins are surely jumping the gun – the two ASCO studies give rise to some interesting questions. Whether statins really can improve survival rates across certain cancers – and if so, how, and for which patients – is likely to loom large in researchers’ minds over the years ahead.
This article appears in the October 2015 edition of Pharma Technology Focus
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