Adjuvant therapy for renal cancer is a difficult one and there has been some new information here on this, here at the meeting. What are your thoughts about this? Let me ask you about the ASSURE trial; first of all tell me what was discovered here?
This was a big study, it was a co-operative study in the USA, and they were looking basically at the benefits of adjuvant treatment in renal cell cancer which was localised treated by removal of the kidney. Then patients who were felt to be at high risk or very high risk of a subsequent recurrence were randomised between sunitinib, sorafenib or placebo for a year.
And what happened?
Well, it was disappointing. The results showed that there was no difference in disease free survival between the three groups. Nearly 2,000 patients were in the study, about 650 in each arm, and the disease free survival was around six years for each of the arms.
How do you explain the fact that there was not such an effect with adjuvant therapy, with these anti-VEGF agents, whilst later in the disease that can be used?
Yes, we know these drugs are very effective in metastatic disease and the hope was that they would be effective in preventing a recurrence of the disease. As you know, with many other cancers we use a lot of adjuvant therapy for high risk patients and the success of these agents later on made us hopeful that they would be useful in this setting. One of the problems is the toxicity of these drugs; from experience patients on them in the adjuvant setting, you can certainly tell they’re on them rather than placebo. They get lots of side effects and, in fact, the grade 3 toxicity was about 60% in the treatment arms in the ASSURE trial. They noticed during the trial that a larger number of patients were discontinuing because of toxicity so there was an amendment during the trial for a dose reduction at the beginning and then a build-up of dose for patients who tolerated it.
Could you tell me about your study, the SOURCE trial?
Yes, in the UK we’re doing the SOURCE trial which is a similar question, it’s looking at adjuvant sorafenib. The difference here is that there is a difference in duration of treatment. We’re looking at either placebo, one year of sorafenib or three years of sorafenib. There’s a similar study in Asia, the ATLAS trial, with axitinib and that’s again looking at one to three years of treatment. So it could be that duration is important, that people weren’t treated long enough in the ASSURE trial. The caveat to that is that many patients had to stop because of toxicity anyway. The median number of months on treatment in ASSURE was only eight months and it was intended to be twelve for the treatment arms. So I think we’ll find in our trials that people struggle to get to three years.
It’s not looking too good for adjuvant therapy in renal cell carcinoma then, is it?
No, you’re right. We need to wait for the results of the other studies and put this information all together but at the moment there’s certainly no role for routine adjuvant treatment outside of a trial.
What should clinicians then make of these results and their optimum strategy to help patients with renal cell cancer?
I think the strategy in renal cell really is close surveillance for recurrence and then treatment and treating the right patients at the right time if they do recur. These drugs are toxic and for patients who are never going to recur or don’t need them the side effects certainly outweigh any potential benefits at the moment.
And the prospects of using other VEGF agents and perhaps mTOR inhibitors?
Well in Asia they are looking at the different drugs like axitinib and whether they have a different role. It’s unlikely they’ve got a similar mechanism. mTOR inhibitors the same probably. They’re also toxic, they have a different side effect profile but I think people will struggle to have them adjuvantly unless there’s a really big benefit from being on them which seems unlikely.
