Advanced Clear Cell Renal Cell Carcinoma: Putting Advances Into Practice - Episode 4

Patient Factor Consideration for Treatment of mRCC

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Daniel J. George, MD: Rana, I wonder if you could comment a bit on what the patient brings to the table. How do you incorporate patient preference into this decision process in terms of goals of care? Neeraj mentioned complete responses [CRs] as an important end point and as a differentiating point from the single-agent TKIs [tyrosine kinase inhibitors]. But is that important in every patient, in every setting? How do you factor in comorbidities and other factors with the patient? What are your thoughts on rounding out this whole discussion with patients?

Rana R. McKay, MD: That’s a key point. With the advent of IO [immune-oncology]/IO and IO/TKI combinations, our end points are changing, and the things that matter are changing. Before, it was largely PFS [progression-free survival] that we looked at. You may get a bit of bang for your buck with OS [overall survival], but it was largely PFS that led to approvals of our VEGF-targeted agents. But we now look at a lot of things. In addition to complete response and durability of response, we're looking at what’s the primary PD [progressive disease] rate? We're looking at what the toxicity profile of a regimen is, what the risks of immune-related AEs [adverse events] are, what the risks of use of high-dose steroids are. Do you have the multidisciplinary team to be able to manage that IO/IO toxicity? What's the toxicity with IO/TKI? What’s the chronicity of TKI therapy toxicity?

All that gets factored in when deciding what the most appropriate regimen is. A patient’s age, fitness level, and goals for therapy matter, clearly. You may have a favorable-risk patient who is young and healthy, and although they're a favorable risk, you still may be swayed to use an IO/IO combination for that individual. You may have a poor-risk patient who may be older and doesn't want to come in and get IV [intravenous] treatment; they live far away from the center, they have other comorbidities, and you’re going to say, “You know what, we're just going to do cabozantinib for you alone from the CABOSUN trial data.”

It's important to understand what the data show us, but there's a lot of gray and art in how we practice in those day-to-day engagements with the patient. You need to understand what you do know, know where the gaps are, and try to come to a therapeutic decision with the patient by interpreting the data and what the patient brings to the table.

Our end points are changing. With the patient populations in all of these trials, all we want to do is sit there and pin them head-to-head against each other and nitpick at every little thing. I'm guilty of that. They're all different. They were accrued at different times, in different parts of the world, with different patient populations, so understanding that is important as you apply it in the clinical setting.

Daniel J. George, MD: That’s fantastic. I agree with you, Rana. This is the art of what we do, right? There is what we might think is the best choice, and then there's the realistic choice that the patient can tolerate and still benefit from it. It's great that we have this spectrum of trials that span across here.

Monty, what are your thoughts on the applicability of these clinical trial data? For these clinical trial patients, if you look at them, a lot of our patients in clinic wouldn't necessarily qualify for this trial or that trial based on some eligibility criteria and other factors. How well do the CheckMate 214 data translate into your off-study patient population?

Sumanta K. Pal, MD: It's tough. The one thing that we’ve become accustomed to doing now in the clinic is screening intensively for any autoimmune conditions. That wasn’t part of my initial dogma in clinical practice, but I struggle with those patients, as one example. It's challenging for me to know what to do with somebody with mild rheumatoid arthritis. Could I potentially challenge them with nivolumab/ipilimumab? I'm tending to favor either TKI monotherapy or TKI plus IO in those cohorts. It's hard to know what to do with patients with poor performance status who might not meet the mark for many of these studies. There I do find myself leaning on nivolumab/ipilimumab to a greater extent, perhaps.

I have to agree with what you said, Dan. It’s challenging to know how to extrapolate from the trial data for some of these unique patients.

Daniel J. George, MD: There have been some studies to look at this: some of our nonclear cell population, some of our brain metastases populations, and some of the poor performance status populations. There are small, single-arm analyses, but at least they're giving us a glimmer of hope that there are some patient populations not represented in the original CheckMate 214 study that could still tolerate and potentially benefit from these regimens. It's not going to be the same result, that 11% CR rate, that good duration of response, and other things. The number of patients who get through all 4 doses of ipilimumab may be lower, but do you still see benefit in these populations?

Sumanta K. Pal, MD: I’ll take a stab at that. There are occasions in which I've been pleasantly surprised by how the nonprotocol patient in my practice responds beautifully to a challenge with systemic treatment, whether it's nivolumab/ipilimumab or cabozantinib in frontline from the CABOSUN trial, but I can definitely cite multiple examples where I've been pleasantly surprised by responses.

Daniel J. George, MD: I agree with you. This is one of the key things, if you treat enough kidney cancer patients, then you’re going to get these exceptional responders, and they're not always in the patient populations that you would predict they would be in. That’s one of the things that’s important out there, not to give up on these regimens because of 1 or 2 negative experiences. There will be those, but if you treat enough patients, then you will see these positive results, and they're life-altering results when you see them, in this frontline setting especially.

Transcript Edited for Clarity