ASCO 2011 Annual Meeting, 3—7 June 2011, Chicago

MD Anderson Institute of Personalised Cancer Therapy

Professor John Mendelsohn – MD Anderson Cancer Center, Texas, USA

You’re really posing an interesting question about all this personalised medicine stuff, never mind that we don’t talk about the patient and the psychological make-up and the educational level of the patient to understand what we’re talking about, are we ready for it all? Are we going to cope with it to deliver it?

Right, well that’s something that I’m very interested in at MD Anderson and in two months I’m going to retire as President and become co-director of our Institute of Personalised Cancer Therapy. And our goal is to set up the operating procedures and do the research so that five years from now every one of our new patients, there are 30,000 new patients a year and some of them have recurrences, we’re going to be able to interrogate the genome of their particular tumour, looking at the DNA changes and metabolomics and proteomics in order to pick the right therapy. And we’ve got to demonstrate we can do this relatively economically and that this pays off in terms of better outcomes and that it will be reimbursed. Now this kind of research that we’re hearing about at this meeting, and it’s wonderful, most of it is paid for by the drug companies or by charity or occasional grants, it’s not covered yet. And it’s going to change and it means that patients are going to have to be re-biopsied. We can cure, hopefully, almost two-thirds of cancer patients now but one-third at the end of five years have lost their life. So these patients come to a point when they’re going to need access to these new experimental drugs and will have to be re-biopsied at that time because the genetic changes in their tumour have changed.

So it’s not just an economic thing, John, it’s a practical, pragmatic, logistic approach to how we deliver this.

Exactly, it’s not systems medicine, it’s systems delivery of care. We’re setting up two or three areas where interventional radiology and endoscopy can biopsy tumours with a pathologist nearby to look at the quality of the biopsy and process it properly. And then we’re setting up a laboratory, a CLIA approved laboratory, that can run these tests and over the next five years we will be adding more and more to this, building on what we’ve learned and what’s being reported in meetings like this, so that, I hope, within five years, that’s the goal, this will become standard practice. 

It will need to be independent of the next gene or mutation that comes along because, of course, in the five years it takes for you to run this and get it functioning there will be five more ASCOs and there are all these… I mean, this is the BRAF this week and it was ipilimumab last week…

Yes, and last year it was ALK.

And that’s going to be fun, isn’t it? How are you going to keep up to date? How’s the technology going to be invested in that is going to be fit for purpose in five years’ time?

A number of ways. First of all, we’re talking to the companies that make the machines that do all these analyses and we’d like to be an alpha or beta testing site. Buying one of those pieces of equipment isn’t the wisest thing, maybe, because a year from now it will be different, they change it. But we’re also going to be carrying out our own research; we have a wonderful model now in the BATTLE trial and now in our phase I trial where we’ll take a patient and interrogate their tumour. Right now we’re testing up to maybe thirty or forty genes, PCRing the individual genes and not doing the whole genome because that’s still a little too expensive and too much information to handle. But we may interrogate, let’s say, for half a dozen genes and we have clinical trials with phase I or II drugs for each of those genetic abnormalities and we can funnel the patient into the right trial. Now the only institutions that can do something like that are large institutions, we’re privileged, we have many, many patients coming, thousands who are looking for experimental therapies. And this approach, it’s called an umbrella, we’re carrying five INDs in some of these trials where we do the original screening and then we funnel patients into the right experimental therapy and the data are very promising. We’ve got to prove that this is better than randomly assigning drugs but we’re confident it’s going to work.

It’s got a gut feeling that it’s the way to go.

Well, when you have these successes but, you know, we’ve been lucky. In something like ALK or now the BRAF, it’s unusual to think that a tumour that probably has fifty or sixty genetic abnormalities in it is changed in its course by addressing one of them. And we all know, I think you would agree, that the real successes are going to require combinations of two and three drugs and that’s going to require, especially in this country, changes in the acceptance of risk by the FDA and by the companies that are going to have mix and match drugs from two or three different companies and by the academicians running the trials. These are complicated trials but it’s the way to go and I think it’s going to happen.

One other thought to add on to your list there, in the European Institute of Oncology in Milan, where ecancer.tv comes from, we’re looking at acceptance of risk by the patient.

Yes.

And how does the patient understand all these incredible outputs in language which suits their education, and then can take part in the discussion. It’s a massive challenge, John, and I’m sure you’ll handle it brilliantly and it will be a massive success. And in ASCO 2016 we’ll hear how it’s going.

Let’s hope so.

I think it’s unquestionably the way to go and, having retired a year ahead of you, I can recommend it.

Good, but I’m not retiring, I’m just switching jobs. 

You’re just moving.

I had a wonderful time being the President of this great cancer centre for fifteen years and now I want to get back to what I started in 1980, one of the very first groups that developed a targeted therapy against an oncogene, working with Gordon Sato at UCSD. We hypothesised we could block the EGF receptor tyrosine kinase.

In 1980?

In 1983, the first publication demonstrating that blocking a tyrosine kinase as a target would reduce the growth of cancer cells. It’s probably the proudest moment in my life. I didn’t know how important it would be at that time but it was very exciting.

Thirty years of fantastic research after that.

Yes, by thousands of people, not just us.

We, of course, are entering a problematic age in that we’re over the age, or I’m over the age, for bone marrow transplantation. So there are a number of issues…

No, no, at MD Anderson people over 70 can still be transplanted. We do the mini-transplant now, it’s not quite as aggressive and it helps the immune system kick out the tumour too. Don’t give up!

John, thanks so much. I’m certainly not giving up, and power to your elbow at your new job, fantastic.

Thank you.