Daniel George, MD: Nick, how do you put all that together? We’ve got 1 positive study, one 50/50 study, and then 1 negative study here. What does that tell us for the field? How do you put all of this together?

Nicholas J. Vogelzang, MD, FASCO, FACP: I’ll be honest, I haven’t treated a single patient with adjuvant sunitinib yet. I’ve seen a few bad-risk patients. But in general, you treat for a year and you get a year of survival. The patient may be a fairly young person who says, “Look, I want to do everything that I can now so that when I relapse, I’ll be around to have the benefit of new treatments.” In addition, there’s still sorafenib’s first trial; there’s still EVEREST coming in from SWOG, and there’s still the axitinib trial. So, it’s possible that we will see those next 3 trials come in positive. Who knows? On top of that, we now have a bunch of immunology adjuvant trials. I think I can well imagine a patient who has… Bob, you told me about a patient you had the other day with 12 positive nodes, a big tumor. That’s a person to whom I’m going to say, “I can give you sunitinib right now,” and I can’t argue with that decision.

Daniel George, MD: You mentioned that it’s 1 year of treatment for 1 year of delay. Did everybody recur?

Nicholas J. Vogelzang, MD, FASCO, FACP: No.

Daniel George, MD: Was there a long-term separation of those curves that suggested there might be a population of patients who persistently remained disease free?

Nicholas J. Vogelzang, MD, FASCO, FACP: No, that was the disappointing thing about the trial. The New England Journal of Medicine was a little bit overly optimistic in their assessment. The survival curves had not plateaued. They were still dropping. And so, I think most of us are scratching our heads and saying, “Well, that’s sort of a positive trial.” It is if it’s PFS you want. But all of us also want overall survival.

Daniel George, MD: Brad, what do you think? You’re a newcomer to the field. You’re looking at this with fresh eyes. What’s your view on adjuvant therapy in renal cell carcinoma? How do you put that in perspective with other solid tumors where we have adjuvant therapies?

Bradley McGregor, MD: I think overall, when you look at adjuvant therapies, your endpoint has to be different. You have to wonder if progression-free survival is an actual and meaningful clinical endpoint. You’re subjecting these patients, some of whom may never recur, to toxicities with a year of therapy, both in the short term and potentially long term with something like a TKI with long-term risks of cardiovascular problems and hypertension, cardiotoxicities. So, if you’re only going to delay someone’s recurrence with therapy and not necessarily prolong their overall survival or increase the chance for a cure, then while I think it has actually met its endpoint of improving progression-free survival, the long-term clinical benefit of that has to be thought about.

Daniel George, MD: I want to be really careful here. I don’t want to say that there’s no overall survival because the overall survival from this study is just frankly immature, right? There has only been about 20% of events for overall survival, so we really can’t say if there’s going to be a signal there or not. If we’re going to see a difference in overall survival, it’s going to be delayed. It’s probably not the worst-case patients who will make a difference on it, but it’s probably occurring later. I think it’s a little bit hard to judge based on that at this point in time.

Disease-free survival in and of itself was an endpoint the FDA accepted. I think it’s an endpoint that some patients are going to be willing to accept and others aren’t. I think the case that Nick brought up was a really good one. There are cases where the patients are young, healthy, and we know there’s a very high likelihood that cancer’s going to come back. I think it’s nice to have this as an option.

On the other hand, there are probably cases where the risk maybe isn’t as high. Maybe it’s T3 only, the nodes are negative, or maybe it’s just a little bit of extracapsular penetration, but not a huge disease burden, of moderate grade. Maybe that’s the situation where you can look and say, “Well, with comorbidities and other things, we can afford to wait on this patient.” I think we’re going to have to personalize these decisions. We’re going to have to look at it in context. We’ve got to let patients weigh in on this because, I think, for some people, they’re going to be a little bit more proactive and want treatment. Others are probably going to be a lot more conservative. Listening and being able to present both sides of that to the patient is really a key aspect. Neeraj, any thoughts on this?

Neeraj Agarwal, MD: I think I agree with you. I think it’s definitely a choice for the patients, and they need to weigh in. At the same time, I have mixed feelings about the results. I would like to see the overall survival benefit in this setting. As Dr. Vogelzang said, 1 year of treatment is 1 year of recurrence-free survival benefit. I think we need to go beyond this. So, yes, this is a choice. This is definitely a very valid option for somebody who is at the highest risk of disease recurrence. There are many patients who cannot travel to come to our center for clinical trials for participation. I think it’s a valid choice. But my preference is to offer these patients clinical trials, which there are many exciting trials ongoing with immunotherapies mostly.

Transcript Edited for Clarity