A magic bullet for everyone?
Greater access to health data, high-tech diagnostics and innovative treatments have led to the emergence of personalised medicine.
Dr Tim Woodman (right), medical director for policy and cancer services at Bupa UK Insurance, explores its benefits, particularly for cancer patients, and the challenges we will need to overcome to make it a sustainable future option.
Personalised medicine is a term that is bandied about a lot, and it means different things to different people.
To me, it’s more than just matching the treatment to the disease. It’s about going a step beyond and making sure the treatment will work in, and with, your body to deliver the outcome you want.
Bringing a treatment into your body is a bit like hiring a new employee. The CV may perfectly match the role description, but performance will suffer if the work environment is toxic.
At one level, this is the function of pharmacogenomics: the rapidly evolving science of looking at how well your body will potentially respond to treatments for a range of diseases.
Pharmacogenomics can maximise the beneficial effects of drugs and reduce the risk of adverse effects.
It is being heavily marketed for many conditions such as hypertension and depression, where the target population is massive, but the cost of the tests (high) versus the cost of the treatments (low) should really see them reserved for those who have failed multiple lines of treatment or who have severe, life-threatening levels of disease.
One Canadian company offers testing against over 200 medications in 19 different treatment areas at a cost of more than £400.
When dealing with cancer, personalised medicine can become highly complex. Again, there are three parties to the treatment – the cancer, the therapeutic agent and the patient.
Targeted therapies
Cancer, even of the same primary site such as bowel, is not identical across all patients. Each cancer must be looked at individually and we have certainly become adept at developing tests that identify mutations in cancer cells so we can hopefully match these to ‘targeted therapies’.
In that case, if the treatments are that targeted, how come only 30-50% of patients respond well?
Even if you identify multiple mutations and pick them off one at a time with different treatments – and ignore the cumulative toxicity – the cancer will probably still progress. Why is this?
When tumours resist treatment and metastasise, this may well be because new mutations have developed that do not respond to the ‘targeted’ agent.
Fortunately, we can now routinely look for circulating tumour DNA (ctDNA) in the blood which picks up mutations from anywhere in the body, including metastases. We may not find the tumour, but we can find its fingerprints.
More accurate tests
‘Treatment failure’ may also be because some of the ‘actionable’ mutations identified were present long before the cancer developed and are part of the ‘background noise’.
There are now more accurate tests that can filter this background noise out – a bit like eliminating the homeowner’s fingerprints at a burglary. This can prevent patients being given ineffective, or even dangerous, treatments.
A significant element in treatment resistance is that many treatments rely on the immune system to finish the job, and some tumours are very good at hiding from the body’s defenders: T-cells.
Immunotherapies, such as immune checkpoint inhibitors, were developed to ‘light up’ these tumours and attract the T-cells. Even then, fewer than half the patients treated will have a significant response.
Unique immune systems
The problem is that there is no ‘one size fits all’ immune system.We’re back to fingerprints again, and immune systems are just as unique and are constantly evolving with subtly changing networks of epigenetic proteins that can enhance or obstruct the ability of immunotherapy to ‘find and fix’ tumour cells for T-cells to destroy.
Your immune system can also be affected by the microbiome of your gut – a healthy microbiome can stimulate a healthy immune system.
Fortunately, it is now becoming possible to test the proposed immunotherapy against both the tumour and the immune system to assess in advance of starting treatment the likelihood that a patient will respond.
This is important for several reasons. These are toxic biological agents that cause significant side-effects in 60% or more patients. It also takes time to decide whether a patient is responding, and these treatments are often used in late-stage disease where time is of the essence.
If you know in advance that a patient is highly likely to respond, you can persevere with treatment in the face of apparent non-response. On the other hand, if the test suggested response would be unlikely, as a clinician you can start the discussion about changing treatment while there is still time to do so.
Suppose you respond brilliantly to treatment, but you will need to stay on it ‘until progression’. This could be for years, with a continuing risk of adverse events and at a massive cost – often £100,000 per year.
Using ctDNA personalised to your cancer, it may be possible to provide re-assurance that the disease really has been eliminated and allow treatment to be paused, while repeating the test at intervals can detect relapse long before it is clinically apparent and enable rapid resumption of treatment.
Everyday practice
This new paradigm presents two main challenges – to insurers in particular.
First, many of these tests were developed to support clinical trials, as they represent more objective ways of assessing treatment response. How do we translate this into everyday practice?
Insurers need to work in partnership with genomics providers, clinicians and hospitals to develop real-world evidence to support the wider uptake of genomics.
Second, how do we ensure we get best value in terms of clinical outcomes and cost-effectiveness? There are many genomics providers out there, with very variable histories.
Again, the answer lies in partnerships between the genomics providers, the insurers and the hospitals to ensure that there are good governance processes in place covering both the adoption of tests and the criteria for their use.
It is also vital that there is clear agreement about the place of these tests in clinical pathways.
None of what I have written here is science fiction – it’s either already here or coming to a clinic near you in the next year or so. None of these challenges is insurmountable and, at Bupa, we are working with our partners to deliver solutions.
Genomics is the biggest thing to hit medicine in my lifetime and it falls to us all to work together to ensure that our patients can reap the benefits in a sustainable, affordable way.