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Sequencing Metastatic Renal Cell Carcinoma Treatments

Panelists:Robert A. Figlin, MD, Cedars-Sinai Medical Center; Sandy Srinivas, MD, Stanford University Medical Center; Nizar M. Tannir, MD, FACP, MD Anderson Cancer Center; Martin H. Voss, MD, Memorial Sloan Kettering Cancer Center
Published: Tuesday, Apr 12, 2016


Transcript:

Nizar M. Tannir, MD, FACP:
As you point out, Bob, it is going to be challenging, not only for people in the community who may see a handful of patients with RCC per year, but even for us in academic circles. You have nivolumab, you have cabozantinib, and you have axitinib. How do you sequence? Which one will be number 2, number 3, and number 4? I think it will be interesting.

And, of course, if the FDA approves lenvatinib plus everolimus, that is also another bona fide regimen to contend with. I would like to add what was mentioned regarding lenvatinib: that the overall survival (OS) with lenvatinib/everolimus was an impressive 25.5 months, very similar to the median OS with nivolumab. So here is a combination, and, in my view, this revives everolimus because we were saying that everolimus got a beating because it was compared with cabozantinib and with nivolumab, and it is falling out of favor. But here, in combination with lenvatinib, there may be a new opportunity, a role for it. So the way I would treat my patients would be that I would choose a VEGFR TKI in the first-line. I think it would be pazopanib based on the COMPARZ and the PISCES data, and from our own experience in using it. Even when you take into account the sunitinib 2-and-1 schedule, I still believe pazopanib is the preferred agent because it’s more tolerable with less hand-foot syndrome, less stomatitis, and, certainly, less myelosuppression. And it’s easier to manage adverse events when you’re giving it on a continuous basis instead of doing 2-and-1; especially managing hypertension.

Post-VEGFR TKI with pazopanib, I would use nivolumab as number 2. I think once cabozantinib is on the market, it will have to be number 3, and then beyond that we’ll see. If lenvatinib plus everolimus came aboard, we might look at it in the third-line or even second-line for some patients. Again, as Martin mentioned, we don’t have to look at just the efficacy outcome from these trials, but also the patients’ own situation, what comorbid illnesses they have. And if they have comorbid illnesses, that would make it difficult for us to prescribe an agent that targets VEGF because if the patient has hypertension and is already on four blood pressure medications or has diabetes, I may go, definitely, with nivolumab as the second-line therapy.

Robert A. Figlin, MD: So, Martin, you’ve heard the MD Anderson approach to metastatic kidney cancer. What’s the Memorial Sloan Kettering approach?

Martin H. Voss, MD: So I think the one important addition that I would make to that is that we can lose sight of the fact that we want to push the field further beyond these new, exciting results that we’ve now summarized here today. And I think the one thing that most of us would agree on that’s important in further developing strategies for kidney cancer is to bear in mind that combinations with targeted immunotherapy, at least for the early data that we have, are showing significant promise. It’s too early to say whether these are going to be lasting effects, but we know that rate of response to a checkpoint inhibitor therapy seems to be higher, at least in the phase I and phase II setting, when it is paired with another agent.

So the one thing that I would add to what’s been said before about sequencing these agents is that we have to bear in mind what clinical trial opportunities patients have. And I think that’s relevant not only for us who are conducting these clinical trials at academic centers, but also for medical oncologists that may be referring patients to us. If you have a patient who is fit and wants to be aggressive about their therapy, then sometimes it may actually not be the best next step for them to go on single agent nivolumab because it can close doors for them to later go into clinical trials that combine checkpoint inhibitor therapies: either two checkpoint inhibitors or a checkpoint inhibitor with VEGF-directed agent.

The one thing I would add, and that certainly is important for my own practice, is that you have to sometimes plan two steps ahead and see—if you don’t have a clinical trial opportunity now—is this the type [of] patient that wants to push the envelope in the future and may want to consider a trial. Maybe then it’s of interest for the patient to first go on cabozantinib knowing that nivolumab will always be an option for them later since it’s FDA-approved. See if there’s a trial that might be available as a next step beyond that before you then give them the checkpoint inhibitor in case that doesn’t pan out. So, certainly, in the frontline setting for now, knowing the data that we have, if I don’t have a trial for the patient, I treat them with a TKI. And I would agree that pazopanib would be my agent of choice.

Beyond that, I think one would see what’s available in terms of combinations. I don’t know that the combination of lenvatinib/everolimus is going to take off. We don’t know yet if there is a phase III strategy at this point or not. But there are other combinations that are going to be very relevant in the very near future, not only in our clinical trials, but some of these trials are going to read out in the future. And that is, I think, of relevance for our patients.
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity
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Transcript:

Nizar M. Tannir, MD, FACP:
As you point out, Bob, it is going to be challenging, not only for people in the community who may see a handful of patients with RCC per year, but even for us in academic circles. You have nivolumab, you have cabozantinib, and you have axitinib. How do you sequence? Which one will be number 2, number 3, and number 4? I think it will be interesting.

And, of course, if the FDA approves lenvatinib plus everolimus, that is also another bona fide regimen to contend with. I would like to add what was mentioned regarding lenvatinib: that the overall survival (OS) with lenvatinib/everolimus was an impressive 25.5 months, very similar to the median OS with nivolumab. So here is a combination, and, in my view, this revives everolimus because we were saying that everolimus got a beating because it was compared with cabozantinib and with nivolumab, and it is falling out of favor. But here, in combination with lenvatinib, there may be a new opportunity, a role for it. So the way I would treat my patients would be that I would choose a VEGFR TKI in the first-line. I think it would be pazopanib based on the COMPARZ and the PISCES data, and from our own experience in using it. Even when you take into account the sunitinib 2-and-1 schedule, I still believe pazopanib is the preferred agent because it’s more tolerable with less hand-foot syndrome, less stomatitis, and, certainly, less myelosuppression. And it’s easier to manage adverse events when you’re giving it on a continuous basis instead of doing 2-and-1; especially managing hypertension.

Post-VEGFR TKI with pazopanib, I would use nivolumab as number 2. I think once cabozantinib is on the market, it will have to be number 3, and then beyond that we’ll see. If lenvatinib plus everolimus came aboard, we might look at it in the third-line or even second-line for some patients. Again, as Martin mentioned, we don’t have to look at just the efficacy outcome from these trials, but also the patients’ own situation, what comorbid illnesses they have. And if they have comorbid illnesses, that would make it difficult for us to prescribe an agent that targets VEGF because if the patient has hypertension and is already on four blood pressure medications or has diabetes, I may go, definitely, with nivolumab as the second-line therapy.

Robert A. Figlin, MD: So, Martin, you’ve heard the MD Anderson approach to metastatic kidney cancer. What’s the Memorial Sloan Kettering approach?

Martin H. Voss, MD: So I think the one important addition that I would make to that is that we can lose sight of the fact that we want to push the field further beyond these new, exciting results that we’ve now summarized here today. And I think the one thing that most of us would agree on that’s important in further developing strategies for kidney cancer is to bear in mind that combinations with targeted immunotherapy, at least for the early data that we have, are showing significant promise. It’s too early to say whether these are going to be lasting effects, but we know that rate of response to a checkpoint inhibitor therapy seems to be higher, at least in the phase I and phase II setting, when it is paired with another agent.

So the one thing that I would add to what’s been said before about sequencing these agents is that we have to bear in mind what clinical trial opportunities patients have. And I think that’s relevant not only for us who are conducting these clinical trials at academic centers, but also for medical oncologists that may be referring patients to us. If you have a patient who is fit and wants to be aggressive about their therapy, then sometimes it may actually not be the best next step for them to go on single agent nivolumab because it can close doors for them to later go into clinical trials that combine checkpoint inhibitor therapies: either two checkpoint inhibitors or a checkpoint inhibitor with VEGF-directed agent.

The one thing I would add, and that certainly is important for my own practice, is that you have to sometimes plan two steps ahead and see—if you don’t have a clinical trial opportunity now—is this the type [of] patient that wants to push the envelope in the future and may want to consider a trial. Maybe then it’s of interest for the patient to first go on cabozantinib knowing that nivolumab will always be an option for them later since it’s FDA-approved. See if there’s a trial that might be available as a next step beyond that before you then give them the checkpoint inhibitor in case that doesn’t pan out. So, certainly, in the frontline setting for now, knowing the data that we have, if I don’t have a trial for the patient, I treat them with a TKI. And I would agree that pazopanib would be my agent of choice.

Beyond that, I think one would see what’s available in terms of combinations. I don’t know that the combination of lenvatinib/everolimus is going to take off. We don’t know yet if there is a phase III strategy at this point or not. But there are other combinations that are going to be very relevant in the very near future, not only in our clinical trials, but some of these trials are going to read out in the future. And that is, I think, of relevance for our patients.
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity
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