ESMO 2012: Vienna, Austria
Advances in advanced metastatic renal cell carcinoma from ESMO 2012
Dr Robert Motzer – The Memorial Sloan-Kettering Cancer Center, USA
Looking at the mRCC landscape, tell us about the findings of the COMPARZ trial.
The treatment of advanced renal cell carcinoma has been an area of unmet need. The disease was formally associated with a very poor prognosis and there really weren’t any treatments to offer patients before about ten years ago. With a better understanding of the underlying biology of renal cell cancer, these angiogenesis agents were developed and found to be effective. The paradigm was really changed with sunitinib which was compared to interferon in a big phase III trial and resulted in a long progression free survival and a high response rate. Since that time there have been other related compounds that have been developed as well. So pazopanib was developed just a little bit later than sunitinib; it was compared in a phase III trial, a little smaller than sunitinib, to placebo but it showed similar progression free survival benefit in that population and a differentiated safety profile. Some of the adverse events that were reported with sunitinib that were particularly troublesome to patients included sores on the bottom of the feet, or hand foot syndrome, stomatitis, fatigue and myelosuppression and in the first phase III trial with pazopanib those were lower incidence than what had been seen with sunitinib. Other side effects, for example liver function test abnormalities, were higher with pazopanib. So this was a head to head comparison between two of the top treatments for advanced renal cell cancer.
How do you think that these data will change current treatment strategies?
The results of the trial showed non-inferiority for sunitinib to pazopanib so basically it means that the efficacy is the same, in my opinion; progression free survival the same, response rate the same, overall survival the same. Side effect profile was different in our trial; some of the side effects that are troublesome to patients like fatigue, sores in the mouth, hand foot syndrome, myelosuppression, occurred at a higher incidence with sunitinib compared to pazopanib. Others, particularly the liver function test abnormality, was higher with pazopanib compared to sunitinib. For the most part the side effects that were differentiated between the two drugs are the ones that affect patients in their day to day function – the fatigue, the stomatitis and the hand foot syndrome. So this was reflected in the quality of life studies that we did where, for the most part, the quality of life analyses favoured pazopanib over sunitinib. So my own feeling is that we have different options now for treatment of renal cell carcinoma. In an era of personalised medicine I think it’s important for the treating doctor and the patient to have an informed discussion in terms of the choice of the medication that’s best for that particular patient. In general though, based on the results of this study, my preference in most patients will be pazopanib over sunitinib in view of the safety profile and the quality of life studies that we showed here.
What changes do you foresee in the safety profile once these findings are used in an everyday clinical setting?
No, I believe that in this 1100 patient trial that was done globally, around the world, many different centres participating, many different treatment doctors, that the adverse event profile and the experience will be quite representative of that of the treating oncologist.
Where do you see the future of mRCC treatment strategies over the next 5 years?
I think that presently main treatment options for patients with kidney cancer and favourable or intermediate risk features have been sunitinib, pazopanib and bevacizumab plus interferon. In the poor risk group the preferred treatment is temsirolimus, based on a trial that we did that was overall survival benefit. But that applies to about 10% of patients, for the other 90% they have a choice between these different agents. There are some other new drugs that are being developed as well that are similar, tyrosine kinase inhibitors, including axitinib and tivozanib. Both of these have been studied in phase III trials, axitinib in the second line setting, tivozanib in the first line setting. I think that these are promising drugs as well, for the most part they as well are focussed on a safer experience, a safety profile. So I think we have to see in the next five years, as these drugs are studied further, how they compare to pazopanib and sunitinib which are the dominant drugs now.
