WIN Symposium 2013

2013 WIN Symposium: 'Innovation to implementation'

Prof Richard Schilsky - ASCO and University of Chicago, Chicago, USA

The theme of this conference is innovation to implementation and I think we’ve seen terrific highlights in both of those domains, really with a focus this year on the challenges of implementing personalised cancer care. What we’ve heard repetitively at this meeting is that the heterogeneity of most cancers is a daunting challenge for us. Each person’s cancer is different from each other person’s cancer and so developing effective treatments is going to be a real challenge because we almost have to do it on a case by case basis. We’ve learned again that although targeted therapies are highly effective when we have a well-defined target and a good drug, that emergence of resistance is a major problem although we’re at least delineating the resistance mechanisms fairly well at this point which should enable us to develop strategies to hopefully overcome resistance.

We’re learning and we’ve heard a call from many of the speakers for sharing of information and I think it was John Mendelsohn, even in his opening remarks, who said that it’s now easier to obtain information than it is to share it because there are a variety of obstacles to sharing information –regulatory, bureaucratic, cultural, social, not technical necessarily. But with all the data being generated and all the clinical encounters that are happening with cancer patients all around the world it’s incumbent on us to figure out how to share all the information that we generate every day to be able to learn the most from each individual patient.

We have to consider each patient’s case in individual circumstances, not only the biology of each person’s tumour, of course, it’s each person’s living situation, their social support networks, their comorbid illnesses and so on. Where the doctor is challenged is to know what to do for their specific patient. What we learn from clinical trials are about new therapies and advances that work for a population of patients that resembles the participants in the clinical trial. But that doesn’t tell you, if you’re a physician, what to do for your specific patient because your patient may not resemble those in the clinical trial and the results of the clinical trial represent an average result for the population being studied and it doesn’t tell you what the result is going to be for your particular patient. So doctors increasingly need a lot of clinical decision support tools. This is going to be increasingly important as we do more and more molecular profiling of cancer. Every day now doctors are getting reports back from laboratories of hundreds of genes, some of which are wild-type, some of which are mutated, most of which the doctor has never heard of. For the typical practising oncologist to be able to understand how to interpret those reports, whether those genes are important or not, whether those mutations are something that they can act on or not, requires that the reports actually be underpinned by a tremendous amount of additional information that the doctor can dig into if they so choose to help them formulate a decision as to what to do for their patient.

And we’ve also heard there are some quite new data coming out in the field of immunotherapy, some antibodies?

Immunotherapy for cancer is, of course, really coming into its own now. We saw this now over the last couple of years with clinical development and regulatory approval of ipilimumab, an anti-CTLA4 antibody, and then, of course, this year we’ve seen lots of excitement with the development of the anti-PDL1 and the anti-PD1 antibodies which function in a similar way by really eliminating the brake on the immune system that prevents the immune system from effectively attacking cancer. Cancer cells, of course, are very wily and they’ve developed mechanisms to evade the immune system over time but I think what these new antibodies coming on now were able to circumvent some of those mechanisms and enable the immune system to find the cancer and attack it. What’s encouraging is not only that these antibodies work across a range of tumour types, so unlike certain types of targeted therapies that only work against certain mutations or only in certain cancers, these new immunotherapy approaches look to have broad applicability. Secondly, although they don’t work in every patient, when they do work the responses to the therapy can sometimes be very long-lasting. Of course that’s been a characteristic of immunotherapy almost since its introduction. If you go back twenty or thirty years to the use of interferon or high dose interleukin-2, the initial very primitive approaches to immunotherapy, oftentimes you saw much the same thing. You saw most patients not benefitting, unfortunately, but a small percentage benefitting for a prolonged period of time.

Now we have a much more precise understanding of the immune system, much more precise ways of interrupting the brakes that tumours are able to put on the immune system and I think we’re going to start to see long term remissions in many patients.

How is WIN involved in some of these new approaches?

WIN is much more than just a symposium. WIN is a consortium of, I think, now 29 major institutions, academic centres, technology partners, business partners, pharmaceutical companies from all around the globe. What’s very exciting to us, of course, is the launch now of WIN’s first clinical trial, the WINTHER clinical trial, which we heard a presentation of yesterday by Professor Soria. That’s a very unique trial, it aims to demonstrate that if one really understands the drivers of a cancer that one can use that information to select a therapy that hopefully will be highly effective in treating each person. Now the unique thing about the WINTHER trial is that it’s taking two different approaches to doing this; one approach is next generation sequencing to look for specific mutations in each cancer which we’re finding about 40% of the time and those mutations may suggest a particular course of therapy. But in the 60% of patients whose tumours don’t have a specific mutation the WINTHER trial uses a very original algorithm for matching drugs to the expression of a set of genes that is unique to the tumour. We’ve already begun to see, even in the first few patients that have been treated so far, unique genes that have identified unique treatment approaches and patients are already beginning to respond to therapy.