IBCD 2016 - Innovation and biomarkers in cancer drug development 

Design and value of immunohistochemical assays

Dr Stephen Hewitt - National Institutes of Health, Bethesda, USA

This year’s conference we’re discussing the development of predictive biomarkers. These are assays that are used to select patients to receive individualised or personalised therapy and the topic I was speaking about specifically is the reduction of these assays to clinically applicable tests, usually using immunohistochemistry.

Could you tell us more about how this selection process works?

We’ve been using different biomarkers; people are actually very familiar with these, they talk about oestrogen receptor for breast cancer, they talk about HER2 for breast cancer but there are other examples. These are used to identify agents that may help drive or direct their therapy – tamoxifen for breast cancer, Herceptin is another example. There are whole new classes of drugs for which we hope to have individualised therapy. The goal is that instead of treating a large number of patients with something that’s relatively toxic, we can identify the patients who are going to… and many of whom will not respond, identify who is going to respond and provide the best therapy we can.

It’s a very fluid field, it’s changing daily. The methodologies are changing, new drugs are coming online and with the advent of immuno-oncology for which there is great success but also great risk, the ability to predict who will benefit from an individualised therapy is really becoming important.

What are your thoughts on personalised medicine in terms of affordability?

This is a very complex debate. Right now one of the challenges in our healthcare environment is obviously cost and economics. We have always balanced that argument by spending more on our therapeutics than on our diagnostics. Sometimes we are penny wise and pound foolish on this, even the Americans would choose pennies and pounds for the description. The issue is that you don’t spend enough on your diagnostics and if you spent more on your diagnostics and selected your therapies better, one, you would have a reduction in overall expenditures on the drugs because you would only be giving them to the patients who were going to need them and benefit from them rather than a larger population which is where the real savings are. But additionally if you can reduce toxicity, these drugs are toxic, and there’s no point in inducing toxicity in patients who aren’t going to respond, you have a negative positive effect. That said, it’s essential that these biomarkers have a discrimination that has beneficial. Right now some of the biomarkers that we’re using for this purpose actually are not accomplishing their goals.

What do you see as the next interesting biomarker development?

Right now the area that’s garnering the greatest interest and excitement is the area of immuno-oncology or what we call immuno-oncology and pathology, IOP for short. Obviously the current agents in development have been focussed on the PD-L1 axis and people have been looking at PD-L1 and PD-1 as predictive biomarkers. Those biomarkers haven’t demonstrated as greater efficacy as we would like them to and, as a result, now we’re looking at other markers that are measuring the immune system and its immune balance. It’s a really interesting time but it’s an extremely challenging time because these new drugs offer a level of benefit for patients who respond that’s never been seen before. Instead of prolonging survival in measures of months and years, patients are virtually cured with some of these agents. So there’s a great deal of pressure on us as well as the fact that the demands on these assays are much higher now. What we’re expecting of the assay and how fast we can develop it is really changing.

The 2016 IBCD conference – how have you found it so far?

So far the conference is very good. The speakers sound as if they were all members of a choir where everybody is giving their individual solo and highlighting different aspects about biomarkers in use in clinical trials. So I think it has been well organised and designed so that there’s a very even and complete message but it’s also highlighting effectively different issues.