Guest post: Cancer immuno-oncology – looking to the future

Wednesday, 23 September 2015

With over 40 years working as a cancer specialist, I have seen tremendous progress in my field. After all we are now able to say, at least in the UK, that 50% of cancer patients will survive their disease for ten years or more1.

However, cancer incidence is dramatically on the rise in the western world especially in middle income countries with aging populations. Make no mistake, what we’re seeing is an emerging crisis. How well we as a society cope with it is the big question.

I look at the future of cancer in terms of four ‘boxes’. The first is the technology, or innovation box, which I’d mainly like to focus on in this article. This includes better diagnostics, less damaging and more precise surgery and radiotherapy. Better personalised medicines is also crucial and of course, better systemic treatment, which is where immunotherapy comes in.

I’m slightly unusual as I did a PhD in tumour immunology back in the seventies before it became a clinical reality. Endless experiments showed some value but I wasn’t seeing actual patient benefit. It was not taken seriously until quite recently with the advent of monoclonal antibodies and then the checkpoint inhibitors where the brakes can be taken off the immune system.

One of the other reasons for the rise of interest in immuno-oncology compared to conventional chemotherapy is the sense that this is the next major ‘new wave’ of treatment, building on what TKIs have delivered. Some TKIs have shown great benefits but on the whole, the actual gain in terms of long-term survival has, so far, been limited.

They have undoubtedly had an impact – it’s been scientifically proven that patients have responded well, but as with many cancer treatments, given the complexity and ‘intelligence’ of the disease to find new pathways the tumour finds an escape route (also known as treatment resistance). But because response rates in immuno-oncology approaches have proved so promising over the last two years, people are less sceptical that these approaches will provide some answers.

However, almost by definition, immunotherapy is least likely to work in patients with very advanced disease because their immune system is already weakened and in most cases they cannot deal with treatment in the time available. Traditional Phase II trials are usually in patients who have failed conventional chemotherapy and these are probably the least likely to respond to immunotherapy. We also need biomarkers to identify the best subgroups to treat early.

Nevertheless, these are exciting times – until five years ago, the diseases we thought would be suitable for immunotherapy were relatively rare ones – like kidney cancer and melanoma – but now it is clear that under certain circumstances, many of the common solid tumours do seem to be amenable to immunotherapy. If you then consider the evolution of combination therapies in immunotherapy, these outcomes will only further improve.

Going back to my view on the future of cancer, the second box is how we deliver care. Almost certainly the way forward is to do so using day centres out in the community – all countries are going down that route. We mustn’t close down our big cancer centres, but rather keep them and devise networks of smaller hospitals or even beyond that for diagnostics, delivery of chemotherapy and follow-up.

The third and fourth boxes are linked. Number three is how much we are prepared to pay for state-of-the-art cancer care and this is something that needs to be addressed. The treatment needs to be affordable to healthcare systems, but equally the innovation that delivers these treatments needs to be properly valued and supported.

The fourth box is the really tricky bit – how we pay for it all. There are only four ways to pay for healthcare – tax (as in Britain), insurance (in most of the rest of Western Europe), cash and charity, with the latter two not sustainable in the long-term. These represent profound challenges for all parties concerned.

For all the current excitement, it is also important to be wary of the hype in the media surrounding immunotherapies. In some cases, patients read positive stories about these drugs, then they come to the clinic and find they are not available yet or that they are not appropriate for their subset of the disease. Patients need to have access to information resources they can trust and that cut through the hype. Websites such as Cancer Research UK and Macmillan here in the UK and the American Cancer Society and the National Cancer Institute in the US are great examples of this.

Our ultimate goal is better prediction of the efficacy of systemic therapy. In 10-15 years’ time future oncologists may have computer programmes which produce a read-out for the patient sitting in front of them, explaining what intervention is best. Eventually we will have something for everybody but it’s just not going to be the same thing for everybody. This underlines the importance of a more personalised approach and combining therapies to achieve maximum impact.