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RCC First-Line Toxicity Considerations

Panelists:Robert A. Figlin, MD, FACP, Cedars-Sinai Medical Center;Daniel J. George, MD, Duke University Medical Center;Thomas Hutson, DO, PharmD, Baylor Charles A. Sammons Cancer Center;David F. McDermott, MD, Dana Farber Harvard Cancer Center;Elizabeth R. Plimack, MD, MS, Fox Chase Cancer Center;Nizar M. Tannir, MD, FACP, MD Anderson Cancer Center
Published: Thursday, Jul 21, 2016


Transcript:

Elizabeth R. Plimack, MD, MS:
I just wanted to counterpoint the point of finding something and getting comfortable with it. I think as oncologists the data changes too fast. I think we should never say we’re comfortable with this, we’re just going to do this. I think we should always be open to data. Certainly you could argue sunitinib versus pazopanib. There’s reasons to use both, but there are also data showing that pazopanib is better tolerated. And it’s surprising I think how slow the uptake was of that practice. So, I think instead of saying find something you’re comfortable with, and don’t change, I think maybe a better approach would be if something new comes around, try it, get a feel for that too, and then watch the data and follow that as that evolves.

Robert A. Figlin, MD: So, Dan, just to bring this session to a bit of a close, one of the keys in our practices has been that we need support staff to help us manage patients with kidney cancer. It’s not just the doctor and the patient, it’s our support staff in terms of our nursing, our extended care practitioners. And a lot of the VEGF and the mTOR toxicities require us to be on our toes, and I think that, as Nizar pointed out, is even more so probably when we start to think about the IO (immuno-oncology) agents. How do you do it at Duke? How does your practice manage these patients in a way that optimizes their outcome and minimizes their side effect profile?

Daniel J. George, MD: Yes, this is really important, and if I can give some pearls of wisdom from our experiences at Duke to share with you, I’d love to hear what you all want to contribute to this as well. I think this is really important because in the community, you probably don’t see near the volume of renal cell carcinoma patients I see because I focus really just in that area. And so we’re able to build up some infrastructure and some insights into this. There are a couple of things about COMPARZ I thought were really important and speak to this. First of all, when you look at the patient-reported outcomes, the worst fatigue they see is with the first cycle. That’s very different than when you give chemotherapy or other therapies, where there’s a buildup of toxicities.

When you’re talking to your patient about starting, and I don’t care if it’s going to be pazopanib or sunitinib, you’ve got to tell them that their worse fatigue is going to be that first month. Because if you don’t, they will go from zero to a lot; they’re going to give up on that drug pretty quickly. So, first off, preparing them for what to expect, and that’s probably true with diarrhea and other side effects, but we don’t necessarily measure them as well.

What we try to do is really front-load the education as much as we can. We have PharmD’s talking with them. It’s very, very important. They talk to them from the drug aspect of it. They talk about how we manage a lot of the toxicities around drug, dosing, and dose exposure, and the timing of when this drug is going to hit its peak, which is different from one drug to the other. We talk about LFTs (liver function tests) and why that’s important. Even though they can’t feel these things, it’s so important to check that at 2 weeks.

And then we have our nurse talk, and it’ll be our clinical trial and a research nurse, or our clinic nurse, or one of our NPs (nurse practitioners) talking more about the practice of what are things to call in for. What are the symptoms to look for? What do you want to see at 2 weeks? We like to bring our patients back at 2 weeks. Now, that may be unnecessary, it may be not practical for a lot of people. But the reality is they’ve never been on this drug before; we’ve seen hundreds. So, we can help them understand, “Okay, this degree of symptoms you’re having is too much and you’re going to run into trouble at weeks 3 or 4.” Or we can say, “You know what, you’re doing fine, we can go for weeks 3 or 4.” Or “Your LFTs are starting to go up already, let’s check them next week because we want to make sure those don’t get out of control.”

There are a lot of things here that happen within the first 4 to 6 weeks that’s critical. Once you get past that window, you kind of know what it’s going to be like. With chemotherapy, each cycle is a little bit repetitive. So, you give the patients a tremendous amount of knowledge up front, you reinforce that with a couple of visits in that first month, and then you can kind of let them go. There are still things that can happen and we still have to watch them, but most of my patients at that point have a personal experience that’s going to help them through whatever lies ahead. That to me is a very, very different kind of practical approach than what we do with our chemotherapies or some of our hormonal agents or other things that have a very different onset of toxicities.

Robert A. Figlin, MD: And I agree with that. In our practice as well it’s not the unusual patient that’s been on for months and even years that says, “I know when the side effects are coming, I know what to do with them, I’ve taken care of it, it’s fine, and I know what you would otherwise tell me.” Tom, you had some thoughts about this?

Thomas Hutson, DO, PharmD: Yes, just to add on to what Dan said. I’ve been fortunate to be an author on some of these earlier publications that looked at the tachyphylaxis or tolerance that’s developed. To be honest, we know the most about our oldest drugs, and our two patriarch drugs were sorafenib and sunitinib. And those have been well studied and we were able to show really that over time, you don’t have the hand-foot syndrome, it gets better. The fatigue gets better. Some of the diarrhea gets better, and there’s a general tolerance that develops to that. So, I agree. And our approach at least at my center is exactly the same as yours and David’s, too.

Daniel J. George, MD: That’s where we learned it.

Transcript Edited for Clarity
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Transcript:

Elizabeth R. Plimack, MD, MS:
I just wanted to counterpoint the point of finding something and getting comfortable with it. I think as oncologists the data changes too fast. I think we should never say we’re comfortable with this, we’re just going to do this. I think we should always be open to data. Certainly you could argue sunitinib versus pazopanib. There’s reasons to use both, but there are also data showing that pazopanib is better tolerated. And it’s surprising I think how slow the uptake was of that practice. So, I think instead of saying find something you’re comfortable with, and don’t change, I think maybe a better approach would be if something new comes around, try it, get a feel for that too, and then watch the data and follow that as that evolves.

Robert A. Figlin, MD: So, Dan, just to bring this session to a bit of a close, one of the keys in our practices has been that we need support staff to help us manage patients with kidney cancer. It’s not just the doctor and the patient, it’s our support staff in terms of our nursing, our extended care practitioners. And a lot of the VEGF and the mTOR toxicities require us to be on our toes, and I think that, as Nizar pointed out, is even more so probably when we start to think about the IO (immuno-oncology) agents. How do you do it at Duke? How does your practice manage these patients in a way that optimizes their outcome and minimizes their side effect profile?

Daniel J. George, MD: Yes, this is really important, and if I can give some pearls of wisdom from our experiences at Duke to share with you, I’d love to hear what you all want to contribute to this as well. I think this is really important because in the community, you probably don’t see near the volume of renal cell carcinoma patients I see because I focus really just in that area. And so we’re able to build up some infrastructure and some insights into this. There are a couple of things about COMPARZ I thought were really important and speak to this. First of all, when you look at the patient-reported outcomes, the worst fatigue they see is with the first cycle. That’s very different than when you give chemotherapy or other therapies, where there’s a buildup of toxicities.

When you’re talking to your patient about starting, and I don’t care if it’s going to be pazopanib or sunitinib, you’ve got to tell them that their worse fatigue is going to be that first month. Because if you don’t, they will go from zero to a lot; they’re going to give up on that drug pretty quickly. So, first off, preparing them for what to expect, and that’s probably true with diarrhea and other side effects, but we don’t necessarily measure them as well.

What we try to do is really front-load the education as much as we can. We have PharmD’s talking with them. It’s very, very important. They talk to them from the drug aspect of it. They talk about how we manage a lot of the toxicities around drug, dosing, and dose exposure, and the timing of when this drug is going to hit its peak, which is different from one drug to the other. We talk about LFTs (liver function tests) and why that’s important. Even though they can’t feel these things, it’s so important to check that at 2 weeks.

And then we have our nurse talk, and it’ll be our clinical trial and a research nurse, or our clinic nurse, or one of our NPs (nurse practitioners) talking more about the practice of what are things to call in for. What are the symptoms to look for? What do you want to see at 2 weeks? We like to bring our patients back at 2 weeks. Now, that may be unnecessary, it may be not practical for a lot of people. But the reality is they’ve never been on this drug before; we’ve seen hundreds. So, we can help them understand, “Okay, this degree of symptoms you’re having is too much and you’re going to run into trouble at weeks 3 or 4.” Or we can say, “You know what, you’re doing fine, we can go for weeks 3 or 4.” Or “Your LFTs are starting to go up already, let’s check them next week because we want to make sure those don’t get out of control.”

There are a lot of things here that happen within the first 4 to 6 weeks that’s critical. Once you get past that window, you kind of know what it’s going to be like. With chemotherapy, each cycle is a little bit repetitive. So, you give the patients a tremendous amount of knowledge up front, you reinforce that with a couple of visits in that first month, and then you can kind of let them go. There are still things that can happen and we still have to watch them, but most of my patients at that point have a personal experience that’s going to help them through whatever lies ahead. That to me is a very, very different kind of practical approach than what we do with our chemotherapies or some of our hormonal agents or other things that have a very different onset of toxicities.

Robert A. Figlin, MD: And I agree with that. In our practice as well it’s not the unusual patient that’s been on for months and even years that says, “I know when the side effects are coming, I know what to do with them, I’ve taken care of it, it’s fine, and I know what you would otherwise tell me.” Tom, you had some thoughts about this?

Thomas Hutson, DO, PharmD: Yes, just to add on to what Dan said. I’ve been fortunate to be an author on some of these earlier publications that looked at the tachyphylaxis or tolerance that’s developed. To be honest, we know the most about our oldest drugs, and our two patriarch drugs were sorafenib and sunitinib. And those have been well studied and we were able to show really that over time, you don’t have the hand-foot syndrome, it gets better. The fatigue gets better. Some of the diarrhea gets better, and there’s a general tolerance that develops to that. So, I agree. And our approach at least at my center is exactly the same as yours and David’s, too.

Daniel J. George, MD: That’s where we learned it.

Transcript Edited for Clarity
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