DR STADLER: For patients who have been on a VEGFR TKI for quite some time and who have progressed, at this time it’s a clear progression. I mean, there are new lesions. This isn’t just a slow growth. I think that the question that always comes up is, do I try a second or a different VEGFR TKI or do I move to an mTOR inhibitor? And it’s not necessarily clear to me what the right thing to do is. There is a tendency based on some of the randomized data to move to a second VEGFR TKI.
DR LOVE: So, generally speaking, what are the agents that you use in this situation?
DR STADLER: I think that the agent that I think about in terms of a second VEGFR would be either pazopanib or axitinib.
DR LOVE: And, Dave, what are your thoughts in terms of second-line therapy and how you decide between a second VEGF TKI and everolimus?
DR McDERMOTT: There’s not great head-to-head data yet with the 2 approved second-line agents. We don’t have a comparison of everolimus and axitinib. It would be good if we did and we could look at the relative value. So we can only infer from other trials in how to use these agents. Generally, if someone has tolerated a VEGF drug and has gotten a benefit we often will follow with the second VEGF drug, whereas if they had grown quickly through a VEGF strategy or didn’t tolerate it well we might switch to a different class of agents. But most patients during their course will see both strategies. And I’m not sure it matters exactly what you do second, because if they didn’t get a TOR inhibitor second they’re going to eventually get a TOR inhibitor as part of their course.
DR LOVE: Bob, how do you think through second-line therapy in a patient who’s gotten a VEGF TKI up front?
DR MOTZER: I think the first established paradigm for benefit was everolimus, based on the RECORD-1 trial. So for the most part in the past, patients who progressed on sunitinib or pazopanib I switched over to everolimus. I think that one of the attractive features of that, to me, was that has a different mechanism of action. And also, I think many patients seem to tolerate everolimus quite well. Other options for patients are axitinib or even sorafenib. It remains an option.
And I think as long as patients can receive 3 lines of therapy, I’m not so sure that it differs whether they get mTOR or VEGF-targeted therapy second or third.
DR LOVE: You also mentioned sorafenib. Could you describe a patient or a situation where you might think about that second line?
DR MOTZER: I think a patient who hypertension is a particular problem with or diarrhea is a particular problem with. Those 2 toxicities seem to be more pronounced with axitinib. And I think again it gets to the point of individualized therapy to the patient.