Advances in advanced renal cell carcinoma from ESMO 2012: Part 3

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Published: 13 Oct 2012
Views: 6712
Prof Tim Eisen - Addenbrooke's Oncology Centre, Cambridge, Prof Bernard Escudier - Institut Gustave Roussy, France, Dr Thomas Powles - St Bartholomew Hospital, London, 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 panel discuss the challenges and potential place of predictive biomarkers in mRCC in order to select the most appropriate drug and maximise drug use. Issues discussed include tissue collection and examination and the pro’s and cons of snip data, measurement of drug levels and the value of plasma biomarkers, such as IL-6.  Professor Escudier notes that predictive biomarkers are unlikely to be found for VEGF inhibitor due to the pathway.


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


ESMO 2012

Advances in advanced renal cell carcinoma from ESMO 2012: Part 3

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

Biomarkers in mRCC

TE:    Biomarkers, Tom I’m going to stay with you. We’ve seen a lot of SNP data, we’ve seen some biomarker data which many people would think too old-fashioned to be interesting but at least we know it works, the drug level data that Brian Rini showed at ASCO. Are any of those going to have an impact, if so which and what other biomarkers do you think would be important?

TP:    The challenges of biomarkers are threefold. Number one is that the tissue heterogeneity and the collection of tissue and when the tissue was taken does not necessarily correspond with what’s happening at the cancer the moment the patient takes the drug. So I think there are huge challenges around examining tissue, sequential tissue, finding a biomarker and applying that to the patient at the specific setting. We really are not doing well in taking fresh tissue in patients and I don’t think we’re going to achieve that which means we’re stuck really with functional imaging, imaging and plasma and, of course, SNPs. At the moment I’m most impressed with the SNP data, I like that SNP data that appears to identify predictive markers associated with axitinib rather than sorafenib. Obviously SNPs can be measured from all patients and they’re consistent. I think it should be pursued more; it strikes me that it’s not an impossible goal to achieve and I’d like to see more work in that area. The second area which I know various people are working on is drug levels and looking at drug levels, finding a very easy way of measuring drug levels. The concern is clearly it’s a more painful and difficult process than just giving drug A but Tom has argued for many, many years that the more you know about your drug the more likely it is to work. I’m quite impressed with some of the data we’re seeing at the moment about adjusting according to dose. Then the final area is the plasma biomarkers. Plasma biomarkers are inherently quite difficult, I think, and some of the IL-6 and some of the IL-8 data that’s been published earlier this year is impressive but the prognostic versus the predictive nature of these is somewhat complicated. I’m not sure we’re ever going to be able to tease out individuals benefitting from drug A versus drug B simply based on IL-6 levels or a change in IL-6 levels so I’m very impressed by the SNP data; I like the drug level data; I’m less impressed with tissue and plasma levels.

TE:    Thank you very much. Bernard, we’ve come a long way.

BE:    Yes.

TE:    Where are we going next?

BE:    I think I will present a little different way as a biomarker. I think we have two types of biomarkers: biomarkers that we have before selecting a drug and the biomarker we have to better use the drug. To better use the drug I think everything about dose titration, drug level and so on will be important but that’s something that will come after we have selected the drug. For me the most important one is before - which drug are we going to select? What we learnt in the past years is that despite we target the VEGF pathway, everything which is on VEGF pathway is not predictive. So I think we probably have to admit that for this treatment we won’t have a very good biomarker, a predictive biomarker. I’m not a fan of SNPs because I think that the time it will take to validate in a prospective fashion the SNPs story is going to be a long time and we’ll have, at that time, new targeted therapy. New targeted therapy like PD1 blockade and some of these treatments are going to be really targeted and we’ll have biomarkers for. So I’m not sure that we are going unfortunately in renal with this targeted therapy, targeting VEGF treatment, we are going to find a good biomarker to select our… That’s my personal opinion at this time.

TE:    So where do you think the whole field is going, Bernard? What are the next exciting things to come up over the next 2-5 years?

BE:    I think probably targeted therapy in renal and that’s something that is probably coming. We have heard very exciting data about PD1 blockade, we have heard something exciting about c-MET and VEGF inhibition, we might have something about FGF and VEGF. At one point, I hope that in renal, like we have in lung or in colorectal, we’ll have some predictive marker for a drug which will help us at the beginning to select one drug versus another one. It’s probably not going to be discriminating between pazopanib and sunitinib which are so close in terms of biomarker.

TE:    OK, thank you. Tom, from your point of view, Transatlanticly, what do you think the next 2-5 years will bring? If we were having the same conversation then, how would things have changed?

TH:    I’m hoping that we’ll see new classes of agents come to the market. I think we all agree we’ve probably reached the pinnacle of development of VEGF inhibitors and mTOR inhibitors and we have come a long way in kidney cancer. We have certainly changed the natural history of the disease and impacted survival but we’re not curing patients. So we need to move beyond that and I think there are a couple of strategies that are in development right now that we’ll hopefully see the results of in the next 2-5 years. The targeted immunotherapy approach with the PD1 ligand inhibitors, like Bernard mentions; looking at novel anti-angiogenic approaches using angiopoietin inhibitors, using vascular disrupting agents, and then understanding more about the resistance which seems to be universal with these agents, maybe finding ways, biomarkers that will categorise patients upfront de novo into which resistance pathways they’re likely to go down, that will help us choose drugs. That’s where I think the FGF and the c-MET and those types of inhibitors that may be critically important in resistance pathways will become useful. All of these areas I’ve talked about are in clinical development right now so hopefully 2-5 years from now we’ll see the results of them and that will add more armamentarium to us and it will change the way we treat the disease.

TE:    On that note I’d like to thank all three of you very much indeed for giving us a tour de raison of a complicated and quickly developing area and I’d like to say thank you for watching and goodbye.