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Frontline Decisions in Metastatic Kidney Cancer

Panelists: Robert A. Figlin, MD, Cedars-Sinai Medical Center; Thai H. Ho, MD, PhD, Mayo Clinic Arizona; Martin H. Voss, MD, Memorial Sloan Kettering Cancer Center; Michael B. Atkins, MD, Georgetown Lombardi Comprehensive Cancer Center; Sandy Srinivas, MD, Stanford University Medical Center
Published: Friday, Sep 08, 2017



Transcript:

Robert A. Figlin, MD: Michael, we have the patient. Sandy has helped us to understand how to think about decision making. Thai has helped us to understand how we think about removing the primary tumor. We know we will have information about their next-generation sequencing, as well as their histology. And we’re left, in 2017, with a large list of options. Many of them are targeted. Most are targeting the abnormalities in kidney cancer that we’ve talked about—VHL [von Hippel-Lindau] abnormalities. How do you start to navigate through that decision making, and what drives you to choose from the agents available?

Michael B. Atkins, MD: In 2017, we’re in a frustrating situation—at least outside of protocols—because we have 2 treatments that dominate the frontline landscape—pazopanib and sunitinib—which have been around for a while. We know that they are very good in terms of prolonging progression-free survival, and can produce responses in 40% to 50% of patients. But, they also have side effects and, for the most part, they’re noncurative. And somewhere between 9 and 12 months’ median, patients are going to progress and need other therapies.

Then we have all these second-line therapies, which are probably better than the first-line therapies, but they haven’t been tested, fully, in the frontline setting. And so, we’re often faced with making a decision of having to give patients treatments that are not the ones we want to give them in order to make them eligible to have their insurance pay for their treatments that we would like to give them.

That’s why, in the first-line setting, I always look to see if there’s a research protocol that’s available. In my view—and this comes from my days of doing high-dose IL-2 [interleukin-2] way back, 20 plus years ago—when approaching a patient with metastatic kidney cancer, the goal is still to try to cure them. I view the other therapies as primarily palliative, so I would look for protocols, if possible, that involve immunotherapy as my first-line treatment as the first approach. If a patient is not eligible for immunotherapy, protocol, or doesn’t have access to high-dose IL-2, and doesn’t have symptomatic metastatic disease, I delay as long as possible starting VEGF inhibitors. If I’m forced to start the standard VEGF therapy, I’m leaning more toward using pazopanib than sunitinib. The COMPARZ study, that we talked about before, indicated that the outcome of both median progression-free survival and median overall survival between sunitinib and pazopanib was similar. Pazopanib is a little better tolerated, and also, from the PISCES study, is probably preferred by patients and physicians.

Unless the patient has liver function test abnormalities, I would probably choose pazopanib, first. If they have some LFT [liver function test] abnormalities, or reasons for which I would worry about their liver, I might choose sunitinib first and, then, try to move toward a 2-week on, 1-week off therapy—instead of the traditional 4-weeks on, 2-weeks off therapy—which is, in general, better tolerated than the standard approved therapy and is now an acceptable alternative.

Robert A. Figlin, MD: Sandy, let’s extend on that a little bit. Again, at the 2017 ASCO Annual Meeting, we had 2 abstracts: one by Dr. Bjarnason from Toronto and another by Dr. Eric Jonasch from MD Anderson Cancer Center. The Jonasch abstract was a prospective 2-and-1 schedule trial. The Bjarnason trial is a trial that we’ve been waiting for—a more tailored approach. Using what Michael said about using sunitinib, do you think these observations change the way you approach the dosing in the schedule?

Sandy Srinivas, MD: I think it’s amazing. We have had these drugs for 10 years, and it’s hard to imagine that we are still talking about dosing. But I think it’s true—we really don’t have a clear idea about what the optimum dose is. Like Michael, we have all moved to dosing sunitinib as 2 weeks on, 1 week off. It’s definitely a better tolerated regimen.

We are very comfortable about dosing down. I think everybody is familiar with stopping at 50 mg, maybe coming down to 37.5 mg, and, then, even going down further. I think the innovative approach is really going up. So, in that trial, they went up to 62.5 mg in patients, provided they were able to tolerate it well and had a pretty good response in terms of the outcome. Therefore, I do think that tailoring it makes a lot of sense. The dose seems to be really important. I think it’s true, going back to the adjuvant PROTECT trial, that the best outcomes were in patients who had 800 mg of pazopanib, so it really seems like optimum dosing is important for a good outcome.

Transcript Edited for Clarity

Brought to you in part by Eisai

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Transcript:

Robert A. Figlin, MD: Michael, we have the patient. Sandy has helped us to understand how to think about decision making. Thai has helped us to understand how we think about removing the primary tumor. We know we will have information about their next-generation sequencing, as well as their histology. And we’re left, in 2017, with a large list of options. Many of them are targeted. Most are targeting the abnormalities in kidney cancer that we’ve talked about—VHL [von Hippel-Lindau] abnormalities. How do you start to navigate through that decision making, and what drives you to choose from the agents available?

Michael B. Atkins, MD: In 2017, we’re in a frustrating situation—at least outside of protocols—because we have 2 treatments that dominate the frontline landscape—pazopanib and sunitinib—which have been around for a while. We know that they are very good in terms of prolonging progression-free survival, and can produce responses in 40% to 50% of patients. But, they also have side effects and, for the most part, they’re noncurative. And somewhere between 9 and 12 months’ median, patients are going to progress and need other therapies.

Then we have all these second-line therapies, which are probably better than the first-line therapies, but they haven’t been tested, fully, in the frontline setting. And so, we’re often faced with making a decision of having to give patients treatments that are not the ones we want to give them in order to make them eligible to have their insurance pay for their treatments that we would like to give them.

That’s why, in the first-line setting, I always look to see if there’s a research protocol that’s available. In my view—and this comes from my days of doing high-dose IL-2 [interleukin-2] way back, 20 plus years ago—when approaching a patient with metastatic kidney cancer, the goal is still to try to cure them. I view the other therapies as primarily palliative, so I would look for protocols, if possible, that involve immunotherapy as my first-line treatment as the first approach. If a patient is not eligible for immunotherapy, protocol, or doesn’t have access to high-dose IL-2, and doesn’t have symptomatic metastatic disease, I delay as long as possible starting VEGF inhibitors. If I’m forced to start the standard VEGF therapy, I’m leaning more toward using pazopanib than sunitinib. The COMPARZ study, that we talked about before, indicated that the outcome of both median progression-free survival and median overall survival between sunitinib and pazopanib was similar. Pazopanib is a little better tolerated, and also, from the PISCES study, is probably preferred by patients and physicians.

Unless the patient has liver function test abnormalities, I would probably choose pazopanib, first. If they have some LFT [liver function test] abnormalities, or reasons for which I would worry about their liver, I might choose sunitinib first and, then, try to move toward a 2-week on, 1-week off therapy—instead of the traditional 4-weeks on, 2-weeks off therapy—which is, in general, better tolerated than the standard approved therapy and is now an acceptable alternative.

Robert A. Figlin, MD: Sandy, let’s extend on that a little bit. Again, at the 2017 ASCO Annual Meeting, we had 2 abstracts: one by Dr. Bjarnason from Toronto and another by Dr. Eric Jonasch from MD Anderson Cancer Center. The Jonasch abstract was a prospective 2-and-1 schedule trial. The Bjarnason trial is a trial that we’ve been waiting for—a more tailored approach. Using what Michael said about using sunitinib, do you think these observations change the way you approach the dosing in the schedule?

Sandy Srinivas, MD: I think it’s amazing. We have had these drugs for 10 years, and it’s hard to imagine that we are still talking about dosing. But I think it’s true—we really don’t have a clear idea about what the optimum dose is. Like Michael, we have all moved to dosing sunitinib as 2 weeks on, 1 week off. It’s definitely a better tolerated regimen.

We are very comfortable about dosing down. I think everybody is familiar with stopping at 50 mg, maybe coming down to 37.5 mg, and, then, even going down further. I think the innovative approach is really going up. So, in that trial, they went up to 62.5 mg in patients, provided they were able to tolerate it well and had a pretty good response in terms of the outcome. Therefore, I do think that tailoring it makes a lot of sense. The dose seems to be really important. I think it’s true, going back to the adjuvant PROTECT trial, that the best outcomes were in patients who had 800 mg of pazopanib, so it really seems like optimum dosing is important for a good outcome.

Transcript Edited for Clarity

Brought to you in part by Eisai
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