New agents for the treatment of advanced renal cancer

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Published: 2 Jun 2011
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Prof Sergio Bracarda - Ospedale San Maria della Misericordia, Perugia, Italy
Prof Sergio Bracarda discusses clinical trials comparing the efficacy of new treatments for kidney cancer such as interferon, bevacizumab, sunitinib and pazopanib. Although combinations of these drugs have produced extremely promising results there have been no comparative studies to identify which combination is most effective. Although advanced kidney cancer is considered chemotherapy and radiotherapy resistant, new radiotherapy techniques such as CyberKnife have the potential to overcome such resistance. Prof Baracarda explains how the new radiosurgery technologies could be combined with the latest therapeutic agents to improve patient outcome.

6th International Kidney Cancer Association Symposium, 6—7 May, 2011, Warsaw

New agents for the treatment of advanced renal cancer

Professor Sergio Bracarda (Ospedale San Maria della Misericordia, Perugia, Italy)

What has changed in the last year is the availability of lots of active and efficacious drugs in advanced kidney cancer, while in the previous years there was the opposite situation with an orphan disease condition. What we have now is acancerous  condition where we have a lot of drugs, all of these drugs are active but what we discuss normally, every day, is which is the best sequence, which drug to be used before and which could be active after. Because what we have now is the modification of the natural history of advanced kidney cancer that has moved from 12-14 months of overall survival six years ago, no more, to actually more than three years overall survival. That is really strange because no study showed, except for the temsirolimus study, an advantage in overall survival. But what we have now is from a point of view a positive selection of the patient from the other, a moving of patients from one line to the other with a significant progression free survival, depending from which drug.

Not all the sequences are the same, of course, and what we are looking to understand now is which is the best , in a few words, how we have to start treatment and in which setting or which  patient. Because we continue to use the Memorial Sloan-Kettering classification for prognostic factors, dividing patients with advanced kidney cancer into patients with favourable disease, intermediate situation and poor prognosis, according to some biochemical and clinical factors. And this is really important to compare the results of these studies. We actually can utilise, in Italy, for example, but also in Europe while there is some difference in the States because of the registration fights of the drugs, three new agents: bevacizumab plus interferon, sunitinib or pazopanib, while in poor risk we can utilise temsirolimus. There are no comparative data now but probably next year we will have the results of the comparative study comparing first line pazopanib to sunitinib and this is really important for us. But at this moment we can start with one of these agents and we have some retrospective evaluation of what could be derived from treating these patients with sequential therapies.

In my presentation tomorrow morning, I will start with bevacizumab plus interferon and we’ll speak about one patient that was entered by myself in the AVERON study, the European study comparing bevacizumab plus interferon to placebo with interferon in a double blind setting. After an impressive positive initial result, on the combination, progression occurred after almost five years, that is really impressive; not the median of the study, of course, it’s a positive selection in this case. After progression we moved to a second line with sunitinib, and achieved sufficient disease control and after the second progression my patient was treated with everolimus and now we are speaking about the fourth line of treatment. What was really important in this case, apart from the positive natural history, is the fact that at the last progression of this patient we had a combined multi-modal approach because the progression was in the bone and we treated this patient together with an orthopaedic oncologist to have a mixed approach. The patient was initially submitted to surgery after radiotherapy to stabilise the situation then  moved on to another medical option. This is one way to understand how the median overall survival in this patient changed because the availability of this new agentshelped make the patient be in fit condition for us to utilise old resources, such as surgery or radiotherapy. And you have to understand that even if normally advanced kidney cancer is considered chemotherapy resistant, and this concept remains, and radio resistant the new techniques of radiotherapy could overcome this type of resistance For example  stereotactic radiotherapy, CyberKnife or other ways of treatment , providing that volume of disease is small can have impressive positive results.

These type of results combined with the new agents could determine the possibility of really positive results in each individual patient. But, of course, what is needed is sufficient experience from the physicians who follow the patient and whohave to decide on the basis, normally of very little data or personal experience of the new modalities.

What we have now in this type of meeting is the possibility to compare data from different experts around Europe and the United States; to have a fusion of data and to have a concept of an expert point of view that could translate in a positive message. Not just  a message to other physicians but especially to affected patients because we are speaking at a congress that is provided by the association of patients and physicians. And this is really also a big difference  also for us because we are looking to the new drugs now to improve treating patients.

Is radiotherapy an option for the primary tumour?

No, the primary tumour is resistant also to medical agents, as was shown in the room now, and also we can utilise focal treatments such as radiofrequency  when there is no place for surgery,  but it  remains the first and most important option for treating primary tumours . Radiation is  a second line option when the risk, for example, of general contra-indications to surgeryexists.