Checkpoint inhibition in practice and in public

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Published: 18 Oct 2017
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Dr Christy Ralph - St. James's Institute of Oncology, Leeds, UK

Dr Ralph speaks with ecancer at the ACP immunotherapy workshop about the implementation of checkpoint inhibitor therapy for cancer patients.

She notes successes for checkpoint therapy in different disease indications, and considers how clinical data from these may inform development for other diseases where checkpoint inhibitors have yet to improve outcomes.

Dr Ralph also considers the challenges facing the UK approvals agency NICE in managing availability and suitability of expensive drugs for sometimes rare disease or patient subtypes, and the role of doctors in communicating with, and on behalf of, patients when incomplete science enters public awareness.

I was talking about checkpoint inhibitors and some of the clinical data that we’ve got from the drugs that are available already and some thoughts about the issues that that leads to going forward, both, obviously, in terms of the excellent patient responses that we see but thinking about the context of capacity within oncology clinics, the funding issues and the regulatory issues and a bit of a disjunct between the very good news story about the patients who do extremely well and the more disappointing story for those patients who have these treatments and don’t benefit from them.

So what kind of inhibitors are we talking about?

We’re talking about checkpoint inhibition so these are drugs which are targeting immune mechanisms which are exploited by cancer to avoid immune control and the drugs are used to reactivate the immune system effectively. So they’re not targeting the cancer directly, they’re using the human immune system to do that job for them. The drugs I was talking about specifically are some of the anti-CTLA4 antibodies, ipilimumab being the one that’s now licensed, and some of the PD-1 antibodies, pembrolizumab and nivolumab being two of the drugs that are licensed.

So you mainly covered the practicalities of using these drugs?

Some of the clinical results showing survival improvement in a number of different types of cancer including melanoma and kidney cancer and some of the more disappointing results, for example in prostate cancer where these drugs don’t look to be of great benefit but there is still evidence of individual responders within that group and seeing if there might be ways that we can look at the clinical data and work out which patients would best benefit from these drugs in the future.

How do we know who will benefit from what?

There’s an enormous amount of research going on at the moment, there are over 1,700 clinical trials registered on clinicaltrials.gov which is one of the big North American databases for clinical trial activity. But I think there’s a bit of a disjunct between the kind of pharma investment in new therapies and new indications and perhaps our understanding of how this will best be applied in the clinical practice within the constraints of the health services that we all work in.

So how do we tackle this disjunct?

That’s quite challenging and I’m hoping that we’ll learn more later in the day, there’s a talk about the economics of the situation which I’m looking forward to.

You mentioned regulatory issues?

There’s a simple issue just of capacity with the number of different indications that are being investigated in the UK through NICE, which is our regulator which makes funding decisions within the NHS in the UK. There are a huge number of different drugs and indications coming through over the next 12-18 months and I think that will keep them very busy.

Do you think NICE needs to be bigger?

I think it would be nice to see some joined up thinking about perhaps the decisions that are made about cost and the ability to negotiate with pharma about that.

Any key conclusions from your talk?

Just that it’s very exciting times and we’ve seen some excellent practice changing results with these drugs. That there is more research coming and that we need to look at the trial design and the real life practice in a lot of careful detail and that as doctors treating these patients we’re well placed to do that. There’s always a difference between day to day practice and trial practice; we all know that not every patient we see in clinic would meet the criteria, the inclusion criteria, to be eligible for clinical trials. We have to be mindful of that when we’re looking at the results of the very exciting research and applying them in our day to day practice.

What do you see differently in the clinic in comparison to what society sees?

There’s a risk that there’s a very different narrative going on in society about amazing cancer results and fundraising for major cancer charities, between that narrative and the individual patient story which we have in clinic and we see, that not everybody we look after is going to benefit from even the great new advances. That can be quite a heart-wrenching thing for people. I think we need to try and navigate that carefully and have that conversation not just on an individual basis but as a group because to some extent we advocate on behalf of them with our patients, both for access to treatments but also to realistic understanding of what benefits they can get from them.