Evidence-Based Strategies for Selecting the Appropriate Frontline Therapy in Advanced RCC - Episode 5

First-Line Treatment in Advanced RCC: Quality of Life Considerations

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Expert panelists consider the importance of quality of life when selecting first-line treatment regimens for patients with advanced clear cell renal cell carcinoma.


Brian Rini, MD: Let me turn to Monty. You brought up quality of life. This is a big topic and kind of a thorny topic. We all agree that quality of life is important. We’d all agree—correct me if I’m wrong—that as you alluded to, the way we measure it is imperfect at best. My question is: how reliable are these data? For practitioners, should they be looking at this to compare regimens? I put up a table comparing response rates. You could argue that that’s not fair, but we do it anyway. With quality of life, how should we be using the data? What’s the value when you boil it down in terms of deciding on 1 regimen over another or just inherently on the quality of a given regimen? We’ll start with you, Monty, then go to Hans.

Sumanta Pal, MD, FASCO: I definitely wouldn’t look at the quality-of-life data in isolation. They do add some general credibility to the story that we’re building for particular regimens. For instance, in quality of life with nivolumab-ipilimumab, without question you see the patients, particularly those who might be on extended holidays or deriving substantial benefit across these various metrics that we’re using. Intuitively, that makes sense.

As you look across, and I’ll use the comparison of lenvatinib-pembrolizumab vs cabozantinib-nivolumab, in my opinion it tells the same story as the toxicity and discontinuation data. When you look at the rates of discontinuation, dose reduction, and so forth of lenvatinib-pembrolizumab, it’s substantially higher than what you see in the context of cabozantinib-nivolumab. It aligns with the quality-of-life data, and you see this modest separation between cabozantinib-nivolumab and sunitinib. But across the metrics that have been presented—it’s what’s out there—for lenvatinib-pembrolizumab, everything is overlapping. I can’t really tease those curves apart. It tells a portion of the story that’s in sync with the remainder, so it’s something we can potentially factor in, although it’s not the be-all and end-all.

Brian Rini, MD: Fair enough. Hans, what do you think?

Hans Hammers, MD, PhD: I totally agree. It’s part of the story. My personal opinion is that you need to titrate any TKI [tyrosine kinase inhibitor] that you use in any setting. The truth is, we sometimes feel 1 TKI is better tolerated than another until the patient complains about the 1 you thought is better tolerated. It varies quite a bit. I can’t predict who’s going to like which 1 better, even comparing across or looking at their treatment history.

The fair thing to say to a patient is to give us a little time, and we’ll find the right dosing schedule for you. That’s true for any agent that you use. You can adjust that, and you can find it. For some of the agents, it’s easier to find simply because you started at a lower dose. With cabozantinib-nivolumab, you start at a dose that most patients end up at anyway if you started them on 60 mg. It’s a regimen where you don’t have to work as hard to find the sweet spot vs lenvatinib, where you’re starting high. You’re starting with the goal to get things to shrink, and then you’re going to probably do a little more work to find the right dosing schedule for the patient.

Brian Rini, MD: I’ll reinforce something you had mentioned previously about dose interruption. Patients are reluctant to stop their cancer pill, and you need to empower them that taking a pill every day isn’t the goal and that if they feel bad, they should stop. I’ve found over many years that those 3-day breaks or whatever recharges the batteries. They make the regimen much more tolerable. It’s not something you can study. It’s hard to point to data, but I don’t know what you guys think. In my clinical practice, pretty much everybody on a TKI long term takes breaks every month, every 2 months, or maybe more frequently.

Hans Hammers, MD, PhD: I agree 100%. I also give my patients the autonomy to almost schedule their breaks. If there’s a certain family event coming up, like July 4, or whatever you think about, the holidays are often sought-after moments with family. They want to minimize the toxicity.

Brian Rini, MD: I totally agree.

Hans Hammers, MD, PhD: So, they get a lot of leeway. Now, patients run into the knife initially. I would say, as you said, patients are highly motivated. They still have to understand that this is a marathon and not a sprint, and so I would say most patients initially make the mistake of going a touch too far in their toxicity exposure, but they learn quickly.

Brian Rini, MD: Yeah, I agree. I usually tell patients, “When you start to feel like you think you might need a break, take it.” For most patients, and it’s usually the spouse who’s saying, “You should take a break.” The patient is like, “I’m going to push 5 more days, 7 more days.” And I say, “You’re not helping yourself.” So empowerment is a nice term for it.

Hans Hammers, MD, PhD: Yeah, and it’s also the spouse. It’s the support system. I work a lot with the spouses. Remember, two-thirds of our patients are men, and they don’t tend to listen too much to themselves or their bodies. Getting the spouses early on into the picture and encouraging the spouse to take a break is absolutely key.

Brian Rini, MD: I agree.

Transcript edited for clarity.