Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)Results of trials evaluating cabozantinib versus everolimus (METEOR) or sunitinib (CABOSUN) for advanced RCC
6:23 minutes.
TRANSCRIPTION:
DR MOTZER: Cabozantinib is a VEGF TKI that also inhibits some other kinases that are felt to be important for resistance, and they are AXL and MET. And there was a very small, multicenter experience that suggested cabozantinib was very effective in patients who had progressed on sunitinib and pazopanib. And so the METEOR trial was a large randomized Phase III trial that compared cabozantinib to everolimus in patients who had had 1 or more prior VEGF-targeted therapies. And the primary endpoint was progression-free survival, which it met. And more recently, it met one of the other key secondary endpoints, which was overall survival. And so it’s a very effective drug, in my opinion. It resulted in a good response rate, prolongation of progression-free survival, and, most notably, improvement in overall survival, which has been very elusive for us to demonstrate in our studies in kidney cancer. So I think it’s a real solid contender now in second- or third-line therapy. The CABOSUN trial was a randomized Phase II study that compared cabozantinib to sunitinib in patients with intermediate- or poor-risk features in the first-line therapy. And it enrolled about 140 to 150 patients. And it showed improvement in progression-free survival and response for cabozantinib compared to sunitinib. So I think that cabozantinib has potential to be an option in first-line therapy for intermediate- and poor-risk patients. In this study, it looked particularly effective compared to sunitinib for patients with bone metastasis. And I think that there are some aspects of the trial that have been pointed out as kind of considerations or issues that need to be clarified. And those, the 2 main ones, are that in this study, the sunitinib seemed to underperform what we would expect. The response rate — in that study, about 80% of patients were intermediate risk. And 20% were poor risk. But the response rate with sunitinib by investigator review was only about 19%. And so in the other studies, it’s been 30% to 40% in some of those trials. And also, the median number of cycles of therapy was less than what we’d expect. It was only 2 for sunitinib. And it’s been longer in the other trials. So we’re trying to ask ourselves why the treatment was, kind of, so short in that population. And why was the response rate so low, 19% compared to 40-something percent with cabozantinib? So what I would love to see is review of the responses by an independent review committee to kind of confirm the activity from that Phase II trial. DR LOVE: We were talking about the fact that people, centers like you, who see a lot of patients — I mean, you have great support, talking about Dr Lacouture — and I kind of have wondered over the years whether maybe people who are more experienced at preventing and managing toxicity might end up actually getting more benefit out of these drugs. Any thoughts about that? DR MOTZER: Yes. I believe that’s true, Neil. I think that, just like anything, the more experience you get with a tool, the better you are at using it. And so I think the tools here are these VEGF-targeted drugs. And with experience, you get a good sense in terms of how to manage the toxicity, when to dose reduce, when to give patients a holiday in terms of stopping treatment for a bit, also when to pull the trigger and start the treatments. Not all patients need treatments immediately. Sometimes we use surveillance, as well as when is the patient not receiving clinical benefit? And having an experience with a lot of the second- and third-line drugs, kind of, what’s the best one for the patient, based on how he’s doing with the first one? So I think that experience is really important. DR LOVE: Getting back to cabozantinib, what’s your experience? And what’s the data show in terms of the tolerability, for example, compared to sunitinib? DR MOTZER: I have probably treated 20 to 25 patients with cabozantinib. I don’t have enormous experience. It’s new. And I participated in a Phase III trial, but we accrued about 12 patients on that trial, and about 5 had had cabozantinib. So I don’t have an enormous experience. I am getting more and more experience now that it’s approved and I’m using it more and more in patients. And I have not had difficulties with using cabozantinib in my patients. And I haven’t really been so impressed by toxicity that was mentioned by others. In my hands, it’s a pretty well-tolerated drug. I mean, I think that some of the side effects seem similar, to me, to sunitinib. There’s sunitinib-type side effects where there’s some fatigue, maybe some diarrhea, some hand-foot syndrome. But I certainly don’t think — I think that more has been made out of the toxicity with cabo than certainly what I’ve been seeing. And I think part of that may have been among the GU oncologists, the initial experience was in prostate cancer with much, much higher doses. So I think it had that kind of a framework going into the trial. But I found it to be a pretty easy drug to use. DR LOVE: Yes. I was going to say, I remember hearing about it in prostate cancer and people saying negative things. I didn’t realize the dose is higher, though. That’s interesting. |