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Personal Approaches to Treating Brain Metastasis in RCC

Panelists: Daniel George, MD, Duke Cancer Institute; Neeraj Agarwal, MD, Huntsman Cancer Institute; Robert Alter, MD, Hackensack University Medical Center; Bradley McGregor, MD, Dana-Farber Cancer Institute; Nicholas J. Vogelzang, MD, FASCO, FACP, Comprehensive Cancer Centers of Nevada
Published: Thursday, Apr 26, 2018



Transcript: 

Daniel George, MD: I want to bring up a scenario that I think comes up from time to time in our field, particularly in this setting where we’re moving from one therapy to another. That is the development of brain metastasis. I bring it up because there have been times when I’ve been denied an MRI of the brain for a patient, and yet I’m always concerned when I have a patient who I’m following and who has a decent disease burden. Maybe they will have progression into a new organ, or maybe they’ve been on a number of different therapies that might select the brain as an organ of sanctuary, particularly I-O therapy. When do you image for brain metastases? Is it only for symptoms, or are you thinking about that as you’re switching from one line of therapy to another?

Nicholas J. Vogelzang, MD, FASCO, FACP: That’s a tough one. There’s no guideline therapy; there are no guidelines. I generally start worrying after my first 2 lines of therapy. I think in the last month, I’ve had 3 patients who all developed a sudden onset of brain metastasis, all of them in that third- or fourth-line space. You usually can salvage them with stereotactic surgery or just surgery alone. It’s not a death sentence anymore. You can pick them up. But, on the other hand, it’s really nice to pick up a 1-cm lesion rather than a 4-cm lesion.

Daniel George, MD: Exactly, exactly.

Nicholas J. Vogelzang, MD, FASCO, FACP: That’s the advantage.

Daniel George, MD: When they’re symptomatic, we’re really late to the game. And to me, if there’s an opportunity to do that—maybe not every single time you’re changing therapies, but if it has been a couple years—check that. Because I think if you do, you’re going to find some of these smaller, incidental ones that we can treat more easily with stereotactic radiosurgery than we can systemically.

Nicholas J. Vogelzang, MD, FASCO, FACP: That’s a good point.

Neeraj Agarwal, MD: As patients are living much longer than they used to, we started seeing an increasing prevalence of incidences of brain metastasis in our patients. The good news for our kidney cancer patients is that they usually have oligometastatic brain metastasis, single lesion, compared with melanoma or lung cancer, where there are multiple brain metastases. I think picking that up early on gives us a chance to treat them easily, when they’re 1 cm in size, with stereotactic radiation versus when they’re 4 cm in size, as you said. We do a brain MRI for all patients once a year who do not have any known brain metastasis.

Daniel George, MD: Even if they’re not progressing?

Neeraj Agarwal, MD: Even if they’re not progressing, once a year.

Daniel George, MD: Interesting.

Neeraj Agarwal, MD: Patients who have brain metastasis, obviously, get all scans every 3 months. Whenever scans are done, we repeat the brain scans. But we learned this the hard way around 3 or 4 years ago when survival suddenly went up from say 9 months to 18 months and then 28 months. I think it’s somewhere in the range of…

Daniel George, MD: Forty months now, potentially, with some of our newer frontline therapies.

Neeraj Agarwal, MD: I think it’s very important to pick them up.

Robert Alter, MD: Histology, also. For our patients with sarcomatoid disease, I’m scanning them every change of therapy. I’ll probably scan them every 6 months, as well, just because you expect that they’re going to be a rapid progressor. If you don’t have a good pulse with your patients, then you find that they’re going to just explode in front of you, unfortunately.

Daniel George, MD: Neeraj, let’s wrap up this session with a little bit of an overview of your strategy now, in terms of thinking about the sequential use of therapies and how you’re thinking about a patient coming off of a frontline TKI. What’s your next move, and how are some of the newer data potentially changing? Are you still going to be thinking about single-agent nivolumab in that setting? Would you think about combinations, especially as some of those data emerge, and maybe get into NCCN guidelines and other criteria?

Neeraj Agarwal, MD: I think I’ll stick to the drugs that are already approved to make it convenient for me. Many things are happening, and I’m sure the field is changing. A similar discussion we’ll have next year will have a very different theme and different ideas and topics. With the current treatment options, I think there are 4 drugs we have: nivolumab, cabozantinib, axitinib, and the lenvatinib/everolimus combination. For somebody progressing slowly—as Dr. Vogelzang said, maybe with 1 new lesion in the liver but otherwise their performance status is stable, with no other symptoms—in those patients, I won’t hesitate to go with axitinib. In patients who have high-volume disease with multiple new lesions, maybe with bone metastasis where I don’t want to take the risk of a drug failing, I won’t hesitate in going ahead with cabozantinib. In fact, cabozantinib is my favorite second-line treatment right now. Where is the role of nivolumab? I think this answer will be much easier next year, when the nivolumab/ipilimumab combination gets approved. That becomes first-line therapy, and then we don’t have to worry about how to choose between nivolumab and cabozantinib in the second line. But for now, I think I’d reserve for nivolumab for those patients whose disease is really indolent and very slowly progressing. I think more so for those patients, I’m already considering axitinib. Those are the patients I’d choose nivolumab for. And then, when they progress on these options, my favorite regimen is lenvatinib with everolimus in the third line.

Daniel George, MD: What do you guys think?

Nicholas J. Vogelzang, MD, FASCO, FACP: I think so. It’s a rapidly changing field. We’re going to be talking about the up-front immunotherapies, and that will change a lot of our discussion over the next couple of years.

Robert Alter, MD: Even in 6 months. Let’s say you have a favorable risk patient, one who on CheckMate-214 did better with sunitinib compared with immunotherapy, and they got 18 months out of it. Do you ever think about immunotherapy, or do you now go back to the philosophy of a TKI followed by a TKI? I’m not writing that study. Thank goodness, going back to what Dr. Vogelzang said: The embarrassment of riches is a good thing to have.

Daniel George, MD: It’s more embarrassing than ever.

Transcript Edited for Clarity 

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Transcript: 

Daniel George, MD: I want to bring up a scenario that I think comes up from time to time in our field, particularly in this setting where we’re moving from one therapy to another. That is the development of brain metastasis. I bring it up because there have been times when I’ve been denied an MRI of the brain for a patient, and yet I’m always concerned when I have a patient who I’m following and who has a decent disease burden. Maybe they will have progression into a new organ, or maybe they’ve been on a number of different therapies that might select the brain as an organ of sanctuary, particularly I-O therapy. When do you image for brain metastases? Is it only for symptoms, or are you thinking about that as you’re switching from one line of therapy to another?

Nicholas J. Vogelzang, MD, FASCO, FACP: That’s a tough one. There’s no guideline therapy; there are no guidelines. I generally start worrying after my first 2 lines of therapy. I think in the last month, I’ve had 3 patients who all developed a sudden onset of brain metastasis, all of them in that third- or fourth-line space. You usually can salvage them with stereotactic surgery or just surgery alone. It’s not a death sentence anymore. You can pick them up. But, on the other hand, it’s really nice to pick up a 1-cm lesion rather than a 4-cm lesion.

Daniel George, MD: Exactly, exactly.

Nicholas J. Vogelzang, MD, FASCO, FACP: That’s the advantage.

Daniel George, MD: When they’re symptomatic, we’re really late to the game. And to me, if there’s an opportunity to do that—maybe not every single time you’re changing therapies, but if it has been a couple years—check that. Because I think if you do, you’re going to find some of these smaller, incidental ones that we can treat more easily with stereotactic radiosurgery than we can systemically.

Nicholas J. Vogelzang, MD, FASCO, FACP: That’s a good point.

Neeraj Agarwal, MD: As patients are living much longer than they used to, we started seeing an increasing prevalence of incidences of brain metastasis in our patients. The good news for our kidney cancer patients is that they usually have oligometastatic brain metastasis, single lesion, compared with melanoma or lung cancer, where there are multiple brain metastases. I think picking that up early on gives us a chance to treat them easily, when they’re 1 cm in size, with stereotactic radiation versus when they’re 4 cm in size, as you said. We do a brain MRI for all patients once a year who do not have any known brain metastasis.

Daniel George, MD: Even if they’re not progressing?

Neeraj Agarwal, MD: Even if they’re not progressing, once a year.

Daniel George, MD: Interesting.

Neeraj Agarwal, MD: Patients who have brain metastasis, obviously, get all scans every 3 months. Whenever scans are done, we repeat the brain scans. But we learned this the hard way around 3 or 4 years ago when survival suddenly went up from say 9 months to 18 months and then 28 months. I think it’s somewhere in the range of…

Daniel George, MD: Forty months now, potentially, with some of our newer frontline therapies.

Neeraj Agarwal, MD: I think it’s very important to pick them up.

Robert Alter, MD: Histology, also. For our patients with sarcomatoid disease, I’m scanning them every change of therapy. I’ll probably scan them every 6 months, as well, just because you expect that they’re going to be a rapid progressor. If you don’t have a good pulse with your patients, then you find that they’re going to just explode in front of you, unfortunately.

Daniel George, MD: Neeraj, let’s wrap up this session with a little bit of an overview of your strategy now, in terms of thinking about the sequential use of therapies and how you’re thinking about a patient coming off of a frontline TKI. What’s your next move, and how are some of the newer data potentially changing? Are you still going to be thinking about single-agent nivolumab in that setting? Would you think about combinations, especially as some of those data emerge, and maybe get into NCCN guidelines and other criteria?

Neeraj Agarwal, MD: I think I’ll stick to the drugs that are already approved to make it convenient for me. Many things are happening, and I’m sure the field is changing. A similar discussion we’ll have next year will have a very different theme and different ideas and topics. With the current treatment options, I think there are 4 drugs we have: nivolumab, cabozantinib, axitinib, and the lenvatinib/everolimus combination. For somebody progressing slowly—as Dr. Vogelzang said, maybe with 1 new lesion in the liver but otherwise their performance status is stable, with no other symptoms—in those patients, I won’t hesitate to go with axitinib. In patients who have high-volume disease with multiple new lesions, maybe with bone metastasis where I don’t want to take the risk of a drug failing, I won’t hesitate in going ahead with cabozantinib. In fact, cabozantinib is my favorite second-line treatment right now. Where is the role of nivolumab? I think this answer will be much easier next year, when the nivolumab/ipilimumab combination gets approved. That becomes first-line therapy, and then we don’t have to worry about how to choose between nivolumab and cabozantinib in the second line. But for now, I think I’d reserve for nivolumab for those patients whose disease is really indolent and very slowly progressing. I think more so for those patients, I’m already considering axitinib. Those are the patients I’d choose nivolumab for. And then, when they progress on these options, my favorite regimen is lenvatinib with everolimus in the third line.

Daniel George, MD: What do you guys think?

Nicholas J. Vogelzang, MD, FASCO, FACP: I think so. It’s a rapidly changing field. We’re going to be talking about the up-front immunotherapies, and that will change a lot of our discussion over the next couple of years.

Robert Alter, MD: Even in 6 months. Let’s say you have a favorable risk patient, one who on CheckMate-214 did better with sunitinib compared with immunotherapy, and they got 18 months out of it. Do you ever think about immunotherapy, or do you now go back to the philosophy of a TKI followed by a TKI? I’m not writing that study. Thank goodness, going back to what Dr. Vogelzang said: The embarrassment of riches is a good thing to have.

Daniel George, MD: It’s more embarrassing than ever.

Transcript Edited for Clarity 
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