Advances in advanced renal cell carcinoma from ESMO 2012: Part 1

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Published: 15 Oct 2012
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Prof Tim Eisen - Addenbrooke's Oncology Centre, UK, Prof Bernard Escudier - Institut Gustave Roussy, France, Dr Thomas Powles - St Bartholomew Hospital, UK, Dr Thomas Hutson - Baylor Sammons Cancer Center, USA

 

Professor Tim Eisen from Addenbrooke's Oncology Centre, Cambridge, talks to ecancer TV with Dr Bernard Escudier from Institut Gustave Roussy, France, Dr Thomas Powles from St Bartholomew Hospital, London, and Dr Thomas Hutson from Baylor Sammons Cancer Center, USA. The experts outline results from the major studies reporting at ESMO 2012 in mRCC. 

 

The COMPARZ study reports on PFS, adverse events and quality of life with pazopanib vs. sunitinib.  The panel discusses how these data compare with those from PISCES, and the implications of these results on clinical practice.  They comment on on-going studies that may lead to an impact on first-line standard of care in mRCC, for example, studies with axitinib and tivozanib. 

 

This programme has been supported by an educational grant from GlaxoSmithKline.

ESMO 2012, Vienna, Austria

 

Advances in advanced renal cell carcinoma from ESMO 2012: Part 1

 

Professor Tim Eisen – Addenbrooke’s Oncology Centre, UK

Professor Bernard Escudier - Institut Gustave Roussy, France

Dr Thomas Powles – St Bartholomew Hospital, UK

Dr Thomas Hutson – Baylor Sammons Cancer Center, USA

 

 

mRCC at ESMO 2012

 

TE:       Hello, my name is Tim Eisen and I’d like to welcome you to this broadcast by ecancer.tv coming to you from ESMO in Vienna. I’ve got with me a wonderful panel of people who will be familiar to you: Bernard Escudier, Tom Powles and Tom Hutson. We’re going to discuss some of the major developments in renal cancer over the last few years and I’d like to start, Tom, with you. What do you see as the current standard of therapy, say, in June this year?

 

TH:       Wow, Tim, OK. So in June of 2012 the standard of frontline therapy for the majority of patients that present with clear cell, the most common histology type of renal cell carcinoma, would be sunitinib therapy; an alternative would be pazopanib but I think the majority usage in the frontline setting, at least from the United States perspective, was sunitinib.

 

TE:       OK, thank you very much. Other Tom, if I may call you that, Tom Powles from Barts, I want to know whether you think ESMO this year is the main kidney cancer conference in the world.

 

TP:       Oh, that’s a different question, Tim.

 

TE:       No, I didn’t think you were expecting that.

 

TP:       No, I wasn’t expecting that. I think one of the things that I feel is that there may be a shift towards both ASCO and ESMO being on parity in kidney cancer. I think it’s important that there are two studies that I’m really excited about, obviously the COMPARZ study is pivotal in terms of treatment choice for first line therapy but Tom’s 404 study, comparing mTOR inhibition and VEGF targeted therapy head to head post-sunitinib, is also kind of crucial. So I would say that right now this meeting is as important as any meeting in renal cancer.

 

New data in first line mRCC

 

TE:       There are a number of major phase III studies reporting, we’re going to start with COMPARZ. How do you interpret the key upfront results of PFS and overall survival as they’ve been reported so far in that study?

 

BE:      I think I interpret that both PFS with sunitinib and pazopanib are equivalent and we  are certainly going to have a lot of discussion  about is one month something different on that. I think all the data we have seen on COMPARZ shows that both drugs are equivalent in terms of efficacy, I’ve no doubt about that, and that’s certainly the main issue from this last study.

 

TE:       So the differences in that study are mainly to do with tolerability?

 

BE:      Tolerability in COMPARZ study I would be a little more suspicious that the design of the study might favour pazopanib compared with sunitinib. So I would be a little more suspicious about the data although what has been reported as adverse events was something that we expected to see from previous studies. I would more base my concern about tolerability on the PISCES study than on the COMPARZ one.

 

TE:       Of which you were the principal investigator so I won’t ask you about that. I’m going to ask Tom Hutson, what is your interpretation, assuming you agree with everything Bernard said about COMPARZ, what is your interpretation of the relative toxicity, tolerability of sunitinib and pazopanib?

 

TH:       Certainly Tim. So I generally agree with Bernard in most things he says and in this case absolutely. So I think the take home points from COMPARZ is that it was a non-inferior trial, both arms were non-inferior to each other, so the efficacy was the same and we would expect that from our clinical use of the agents. Tolerability seemed to be in favour of pazopanib; that to me was supported by the PISCES trial that we heard about at ASCO this past year where we saw both in a blinded fashion and in a novel trial design that both patients and physicians chose pazopanib as a preferred therapy after really two cycles of treatment. Now, as Bernard mentioned, when we start talking about quality of life, an area which is somewhat in its infancy stages in cancer trials, we’re using unvalidated instruments, there are a lot of  critiques that could be done with this. But I think the take home message from both PISCES and COMPARZ generally supports what we as physicians see in our practices: that in general patients seem to tolerate pazopanib better than they tolerate sunitinib; the efficacy seems to be similar. So really we really have now two great drugs available for our patients.

 

TE:       OK, so you would accept that pazopanib is better tolerated and preferred from the patients if you accept the PISCES outcome?

 

TH:       Yes, because again think what would make the individual doctor accept it or not accept it, given that there are going to be flaws in every study we do, is what you see in real world experience. So the results of both PISCES and COMPARZ mirror what I see in my own practice so I think that they’re valid.

 

TE:       OK, thank you. So we’ll come back the US view of how this is going to change things but Tom, how will this change things, or will it change things, in Western Europe, say, or Central and Western Europe?

 

TP:       Yes, I think that’s an important question and I think one of the things that impresses me about the way that pazopanib has been developed is this dual approach, one with the randomised phase III non-inferiority showing that one drug is no worse than another and the other elegant design that Bernard led showing a patient preference of 70% versus 20%, which is quite a big difference between the two. Together this supports the notion  that perhaps pazopanib is actually much better tolerated than sunitinib and if the drugs are effectively similar and it’s a palliative setting, and ultimately the life expectancy is  still only 28 months, tolerability actually and quality of life becomes perhaps as important as any other factor, all other things being equal. So I think it will change things in Europe,  I think people will look at this data, many people have been waiting for the COMPARZ data before they switch from sunitinib to pazopanib, and my feeling is many people will do that. The data reflects my personal experience of using both drugs in 100-120 patients, however many it is, so I’m not surprised by these results, they reinforce what I’ve seen. So there’s something very credible about what we’re seeing today and what we saw in PISCES and I think people will be convinced by that.

 

TE:       OK, thank you. Before I come to you, Bernard, I’d just like to come back to Tom. Is that going to be the case in the US as well or will there be a difference, do you think?

 

TH:       I think so, I think right now if we just go across whichever company you want to use, the market data, it looks like sunitinib has a much more firmer foothold in the United States than it may in Europe. So I think the data from ESMO needs to be disseminated and understood by the community oncologists in the United States who may not be following ESMO closely. So I think with appropriate education of the results of ESMO and getting doctors to actually attempt to use the drug would result in a change also in favour of pazopanib. But I don’t think it will happen as quickly, probably, as it will in Europe.

 

TE:       OK, thank you very much. So Bernard, did you want to add anything to those comments before I ask you your next question?

 

BE:      No, I think it’s fine. I don’t know if it’s going to be faster in Europe than it will be in the US because Sutent is really well implanted and it’s a drug that many oncologists have used and know how to use it, even though it has toxicities. So in the world for disseminating this information is going to be as important in Europe as it is in the US.