The promise of immunotherapy for elderly patients

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Published: 15 Nov 2017
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Dr Alistair Greystoke - Newcastle University, Newcastle, UK

Dr Alistair Greystoke talks to ecancer at SIOG 2017 in Warsaw.

He discusses the benefits of immunotherapies, with a focus on older caner patients. 

Dr Greystoke highlights that there are not enough clinical trials with older patients taking part. 

He goes into deeper details about the response biomarkers for immunotherapies.

The future prospects of immuntherapies are good, and Dr Greystoke touches on some of the ways progress is being made.

This service has been kindly supported by an unrestricted grant from Janssen Oncology.

We’ve got new drugs called immunotherapies which use the immune system to attack the cancer rather than attacking the cancer directly like chemotherapies. These are coming forward in a large number of indications; they started off in skin cancer, melanoma, but are now coming forward to more and more of our patients – lung cancer, head and neck cancer, kidney cancer and others coming along. The question that’s now arising is these drugs seem to have less side effects than chemotherapy in general, what’s their efficacy and what’s their side effect profile in the older patient? Particularly in cancers like lung cancer the average age of lung cancer in the UK is 71, so a lot of our patients are in the older age group. Unfortunately, many of the clinical trials still exclude these patients and so we’re lacking data as to how well these drugs work.

We know that the immune system changes as we get older and that T-cell function changes and obviously using immunotherapies we’re relying on the T-cells and the right type of T-cells to identify the cancer and bring in other aspects of the immune system to kill the cancer cells as well. We know that these all change as you get older. In animal models it does appear that cancers can become more difficult to treat as you get older. Our experience in the older cancer patient is still relatively limited. We’re starting to get some cohorts coming through, particularly in the age group 70-75 which is just actually they may work just as well in this age group. What we are still really lacking on data in is the patients over 75. There has been a meta-analysis that suggested that they might not do quite so well but at the moment the data is just not really out there and we need more clinical trials to address that population.

What markers help us predict if there will be a response?

The classic markers we look for at the moment are in the patient’s tumour which is PD-L1 expression but that’s a relatively crude marker of the tumours and interaction with the immune system. We’ve got increasing markers coming through such as tumour mutational burden but again that’s just telling you a lot about the tumour. You can start to look at T-cell subsets to try and work out how immune senescent the immune system is and that may be an interesting factor going forward.

What can the performance status tell us?

Performance status is very difficult to assess in the older patient because you start to get the impact not only of the cancer but of their decreasing physiological reserves as they get older. We know in the younger patient with performance status 2 that they do badly or much less well with these immunotherapy agents and that’s probably because their tumour has got lots of information and may not be the right type to respond to these immunotherapies. But what about the older patient who is performance status 2 because of their comorbidities or decreased physiological reserve? Again we just don’t really have that data. These are the patients who we’d really like to be able to treat with the immunotherapies because they’re very difficult to treat with chemotherapies.

Does coming to SIOG help you towards getting access to some valuable tools?

Yes, there are a lot of tools out there that can help us to assess the older patient better in terms of their physiological reserve and their potential to undertake treatment. Unfortunately, most of these tools are not yet implemented into routine clinical practice but there’s huge potential for collaborations here.

What should a geriatric watching this look at to find out more information?

Coming forward I’m sure there is going to be co-operatives coming together like the CARG group to identify risk scores for patients undergoing immunotherapy. But many of these will be academic led studies looking at the role of immunotherapy in the future. There’s a very nice study running at the Christie called the ELDERS study looking exactly at this question.