Key research from ESMO 2010

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Published: 1 Nov 2010
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Prof Jim Cassidy - University of Glasgow, UK
Prof Jim Cassidy speaks about some of the research presented at ESMO 2010. The first was a well designed trial looking at pancreatic cancer in metastatic or locally advanced patients. This three armed study assessed two novel agents, conatumumab or AMG 479, combined with gemcitabine and demonstrated that the IGF-1 inhibitor AMG 479 was clearly superior. Prof Cassidy also speaks about a Canadian presentation on cost effectiveness, discusses how study design should be modified to improve results for colon cancer and talks about advances that have been made in the early detection of colon cancer.

ESMO 2010


Professor Jim Cassidy - University of Glasgow, UK


Key research from ESMO 2010



Professor Jim Cassidy from Glasgow University, welcome to I know you’re in a terrible rush, you’ve been judging posters and giving talks and so on. Just take a couple of minutes. Were the poster sessions interesting?


Yes, there were some good things at the posters yesterday. And strangely I was judging the non-colorectal things, which is not really my speciality area.


Not a bad idea.


A pretty good idea actually, it made me broaden my horizons a little bit. But it was still GI cancer so I kind of understood, I haven’t lost it completely. The best one, I thought, there was one that came from the States and it was pancreas cancer, and it was very clever. It was a three-arm study looking at two novel agents in combination with gemcitabine, so a novel agent, gem versus another novel agent and gem versus gem and a placebo, all in the same study. So an internal control, if you like. And novel agents which have some rationale behind them, and they were doing a pick-a-winner.


Were they K-RAS ones?


One of them was an IGF-1R inhibitor, and one was death receptor 5 inhibitor. So a pick-a-winner design in pancreas cancer which you’d think, well what you’ll get is all three of them lose because that’s what we’re used to in pancreas cancer. But no, they get a clear winner in one of the agents, the AMG 457 I think its codename is, so they’re going to take that forward now into a bigger trial.


And was that the IGF inhibitor?


It was the IGF inhibitor yes, and of course that isn’t maybe what you would expect because IGF inhibitors look like they’re active in others, including my own disease.


And these were inoperable pancreas, or were they metastatic?


These were metastatic pancreas patients, locally advanced or metastatic.


OK, so that’s a good result then, that’s quite encouraging.


And a very clever design of trial, I was quite buoyed up by that and the presenter was able to answer all the questions. Usually when you try to grill them to find out what mistakes they’ve made, she was very smart and had all the answers.


I think the Americans are slightly better rehearsed than our young people, defending posters in Europe. So, the next one? Anyone?


And then there was a cost-effectiveness thing, so a different thing altogether. This was a Canadian group looking at cost-effectiveness of interventions in their own practice. The Canadians, because of the way their health care systems work, they’ve got a really good handle on being able to say, “So in our region there’s this numbers of cancers; this is what happens to them and here’s what the outcomes are and here’s what the cost-effectiveness is of an intervention.” I like that, really because we’ve done some of that in Europe, that cost-effectiveness type stuff.


You’ve done it in Glasgow, yourself.


We’ve done some of it ourselves, yes. And the Americans haven’t really got the wherewithal to do that, the North Americans haven’t, because their healthcare is all a bit disjointed with private practice. So the Canadians are leading the way for North America in that whole technology and it was very nice and the poster was very well presented, Markov designs and things, which are quite complex to get across to people, were there all in little cartoons, it was lovely, really nice.


Good stuff. And anything else that has caught your eye around the place in the sessions?


Unfortunately some negative things. There’s the colon cancer with another couple of negative trials, the HORIZON trials with cediranib which I was involved in and unfortunately they’re negative.


But they have to be presented and published and this is something which I was seeing for the first time at ASCO this year, that actually giving space to negative trials.


Oh, for sure.


And I thought that was really helpful.


And in colon cancer we’ve had a little bit of a patch of negativity, if you like, but none of us have really been put off by that because what we’re trying to say and what we’re getting to is we’re probably not doing this right. What we need to do is spend a bit more time trying to find the molecular markers that will select out the right patients; doing the big phase II and phase III things on unselected patient populations looks like a bust, generally looks like a bust. So we’re now at the point where we will spend more time and energy trying to say, let’s do the biomarker thing, and not do the drug trial until we’ve got the biomarkers in the bag because otherwise we’ll just keep doing this, we’ll keep doing negatives and negatives and that’s not good for anybody.


And of course you’ve got a very strong drug development, drug discovery group in Glasgow. The same applies really to study design in phase I and phase II, doesn’t it? Or phase 0 if you like.


Yes, clearly if we can enrich the populations and then we’ve got the logic, given the rationale for doing it, it makes sense to do that right from the word go, it makes sense to do it, actually, pre-clinically, of course it does, and then take it into the clinical arena. I guess there’s a bit of me, the cynical bit of me, which says, “Yeah, but we only know what we know and we don’t know what we don’t know,” and quite often what we do is we find as we go along in the drug development process, we find something else that then changes what we thought about how rational and logical it was.


But nonetheless that’s not a reason not to pursue logic. One has to say somewhere along the line, we’re going to do this in some logical fashion, otherwise you just do everything in some sort of random way and hope for the best.


Silvia Marsoni was interesting when I interviewed her for the ESMO newsletter. She was saying that, as far as she’s concerned now, the main direction of dialogue between the lab and the clinic is from the clinic to the lab and not the other way round and I thought that was quite an astute remark.


I think that is, to some extent, true and I think that balance changes with time. What happens is the lab guys teach us things and we then think, OK, so we’ll take that into the clinic and we’ll use that. But then we learn extra bits and we need to feedback to them and of course it’s an iterative loop but the balance changes from time to time, depending on just where you’re at. Certainly in colon cancer, for quite a long time in colon cancer we had a purple patch where we had lots of new things that worked and we were feeding lots of things back to the lab guys. Now we’re at the point where we need them to feedback and it will help us.


You’re listening. One of the purple patches, of course, was aspirin in chemoprevention and you are involved and passionately interested in screening and early detection of colon. You did some very early stuff, I gather.


Yes. Clearly we’ve been involved in the screening that the FOB and colonoscopy screening in Scotland has now taken that on board. We’re doing that with everybody over the age of 50. That’s having the really predictable results that we thought it would have, at least in the first wave of screening, but that’s not going to be the end. People don’t like FOB tests, the public don’t like them and are not terribly compliant so we really need blood tests, I think, to be able to do this. This new technology is looking at blood testing and looking at exosomes essentially. There’s quite a long track record of exosomes being shed into the blood stream and those exosomes and what do they mean and have you a way into saying, we can understand the biology of the tumour by looking at something in the blood? To cut a long story short, this looks like it might be the crack that we need to get in there.


What kind of exosome analysis is it?


They’re doing the usual thing, they have to select out these exosomes. Part of the trouble that has always been for, say, twenty years has been that they have been very hard to get these out of the plasma because they tend to be lipid based so therefore they’re difficult to separate out. This particular company have a way now of separating them out which they feel is reproducible and authentic and then doing on those exosomes, then looking at the surface molecules of those exosomes and saying, so those surface receptors match the surface receptors on the cancer cell, or do they? If they do, then we can then start to predict what would happen to the cancer under the influence of treatment X or treatment Y. So it’s, to coin a phrase, a liquid biopsy, which I think would be a really good thing if we were able to do that.


What sort of turnaround time would you be to get the analysis?


Two or three weeks. It’s not enormous.


And costs? Always important in Scotland.


Don’t know. It’s all early yet and I’ve been in drug development for a long time and, as you know, cost comes into it but we wouldn’t stop a project early on saying, “Oh this will be too expensive,” because technology moves quickly and expensive technology today becomes tomorrow’s really cheap technology. And I think these things will all go that way. Certainly, if you can find value in something like that, people will find ways of doing it slicker and quicker and cheaper.


Yes, sure. Jim, thanks very much indeed, I really appreciate just a wee chat with you, catching up again.


Nice to meet you again.