Bladder Cancer Update & Renal Cell Cancer Update, 2017 (Video Program)Response to immune checkpoint inhibition, duration of therapy and immune-related adverse events in RCC
5:54 minutes.
TRANSCRIPTION:
DR LOVE: I’m going to throw out a few things I’ve heard from your melanoma colleagues and lung colleagues, et cetera, et cetera, and see what your experience has been, if any, with these problems with renal cell cancer, starting out, number 1, with colitis. It sounds like it’s not very common, unless you bring in an anti-CTLA-4. Have you seen clinically significant colitis? DR MOTZER: I’ve had a fair amount of experience with the ipi/nivo combination in the trials for renal cell cancer. And we definitely do see it in that situation. But I do have to tell you that we’re becoming more and more used to it and able to manage it as well. And so I think as long as it’s recognized early and adequately managed, it’s a manageable toxicity. I haven’t seen colitis, per se, with nivolumab as a single agent. DR LOVE: What about endocrine issues, including hypophysitis? DR MOTZER: I see those more commonly. Again, we see them more with the combination with ipi/nivo, but we do see hypothyroidism and some of the manifestations with pituitary insufficiency and adrenal insufficiency, but again, much more with the combination. DR LOVE: What about dermatologic issues? Again, I’ve heard they’re, quote, not that uncommon but not that difficult. DR MOTZER: Patients often develop kind of a dry, itchy rash. And for the most part, we’re able to manage it with topical steroids and again, relying on our colleague Mario Lacouture to help us manage those. And occasionally we utilize short courses of steroids, but generally it’s topicals. DR LOVE: Neurologic problems? DR MOTZER: So those are the trickiest to diagnose and the trickiest to manage. And we have seen those, some demyelinating disorders and so forth, from these drugs, which can be serious. DR LOVE: Another issue that goes across tumor lines that comes up with these agents is the question of utilizing them in people with prior autoimmune diseases. And, of course, second-line therapy of renal cell cancer is not a good situation, although there are other options. Have you encountered people with Crohn’s disease, multiple sclerosis? And how do you think that through? DR MOTZER: So I have not encountered that yet in clinical practice. But for the most part, I mean, I have concerns about that. And if a patient has an active autoimmune disorder, I would probably avoid the use of nivolumab in that patient. I know there is 1 publication that I’ve seen that indicates that it can be safely given, although there is a higher risk of complication. But in renal cancer, as long as there are other options, I would utilize those first in a patient with active rheumatologic disease. DR LOVE: It’s interesting. When I first started asking people, everybody would say, “Those people were left out of the trials.” And then as the drugs came in practice, you started to see data coming out. And it kind of does seem like it often flares up, prior autoimmune disease, but as you say, it’s kind of a tricky tradeoff to think through. Globally, when you start a patient — a typical second-line situation — on nivolumab, in your mind what’s the likelihood that the patient’s going to have a prolonged progression-free survival, let’s say over a couple of years? DR MOTZER: I think the progression-free survival is probably not the best metric for nivolumab. So I look to the response rate, more of the durable responses, with the response rate being about 25%. And I think probably about half of those responses are durable. So, I mean, it’s not — with single agent it helps patients, but it doesn’t help the majority of patients. Most patients don’t achieve a durable response. I think it’s possible. It provides hope to all of us, but it’s not most patients. That’s why we need to do better. DR LOVE: Yes. I mean, but 10% is a lot more than zero. And, I mean, do you think there are people getting cured? I mean, do you have people who get CRs who stay in a CR for a couple of years? DR MOTZER: Yes. I mean, we do have patients that have long-standing responses to nivo, although I can tell you that I’ve seen that more with the combination of nivo/ipi in the trials. And one of the patients that is under my care that was treated on the very first Phase I study — that is public; it’s published — he had progressed through VEGF-targeted therapies. And I didn’t think he had much time left. And we treated him on that Phase I trial with ipi/nivo, and he achieved a complete remission. That was back about 3 years ago, and we recently stopped his treatment and following him along. And I think he may be cured. So I think it’s possible, but I think it will be more likely as we go into these combinations. DR LOVE: I was going to ask you what you do with these rare patients in terms of stopping therapy. Any general guidelines? DR MOTZER: We don’t have them yet. I mean, for the most part if the patients are doing well and they’re tolerating the treatment with nivolumab, with sunitinib, with pazopanib, we continue them on the medication. I think there are more ground rules from the melanoma group in terms of duration of therapy. We don’t have those in kidney cancer. We haven’t gotten the experience. And so in my own practice, if the patients are responding and they’re doing well, I continue them on the therapy. |