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Goals of Therapy for Advanced Kidney Cancer

Panelists: Robert A. Figlin, MD, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center; Eric Jonasch, MD, University of Texas MD Anderson Cancer Center; Toni K. Choueiri, MD, Dana-Farber Cancer Institute; Michael R. Harrison, MD, Duke Cancer Institute; David I. Quinn, MBBS, PhD, USC Norris Cancer Hospital
Published: Wednesday, Mar 22, 2017



Transcript:

Robert A. Figlin, MD:
So, Michael, that gets to a larger conversation around what we consider tolerance to therapy. Maybe what are our goals for treatment, how do we assess quality of life, and how do we integrate that into the approaches that we give? Give us some thoughts in terms of this plethora of agents that we have available, how that plays a role in choosing agents and designing a paradigm for an individual.

Michael R. Harrison, MD: On the topic of tolerance, I think it’s abundantly clear that not all patients tolerate these drugs the same. For the most part, we’re doing flat dosing right off the bat. With the exception of axitinib, there is a dose escalation. A 105-pound woman may tolerate these drugs much differently than a 250-pound man. You did raise the issues of goals of care, and I think that’s a really interesting topic that has been somewhat explored, but we could really go deeper. If you ask patients, “What is your goal?”, different patients have a different balance between prioritizing quality of life versus tumor response variables or outcomes. So, I think it’s important to understand a patient’s goals of care, to understand what therapies you’re putting them on. I certainly think acute supportive care is necessary to manage some of the side effects like diarrhea. But I think one thing we’re realizing is that as patients go into second-, third-, and fourth-line therapy, there are some common themes. One of those is fatigue that’s going across all lines of therapy. And I know we’ve all had patients who have gone through 5 lines of therapy and they wind up in a wheelchair, possibly somewhat from the tumor, but I would also argue from some of the therapies as well. I think we could do better probably with addressing lifestyle changes early on, whether it’s nutritional strategies or exercise strategies, to try to mitigate some of those things like fatigue.

Robert A. Figlin, MD: David, at USC, give me a sense of what the conversation is with the patient now that we have survival data. We’re not talking about either response rate or progression-free survival, endpoints that may be important to the oncologist, but not as important to the patient. How do those conversations go?

David I. Quinn, MBBS, PhD: I think the conversation has evolved recently and fairly significantly. We’ve always had the risk-benefit conversation. What are the risks of you getting side effects that are going to be significant versus us controlling your disease and prolonging your life? We’ve not demonstrated overall survival definitively until very recently with the 2 trials with nivolumab and with cabozantinib. And so, I think it is a different discussion. From that perspective, I think that many patients still get into the paternalistic stuff saying, “Well, look, I’ll take the medication and I really don’t need to have the discussion. Just tell me what I should do.” Throwing the stuff out there to say, “Look, there’s a balance here. We may make you, in some cases, sicker than you really need to be, and the treatment may be worse than the disease,” I think telling them that puts them into a position where you can have that therapeutic discussion. “What’s the balance when we’re seeing you now? We’re controlling your cancer based on the scan and your symptoms from the disease, but what are your side effects and how do we balance that out?”

Robert A. Figlin, MD: Eric, what are your thoughts around when to start? We have this concept now that has been reported of so-called active surveillance. When we know the cancer is there, we know the person has had a distant nephrectomy, the biology of the cancer may be slowing growing. Some people think you should start immediately, some people think you should wait. Where do you come down on that conversation?

Eric Jonasch, MD: There are a couple of abstracts this year at ASCO GU that are addressing that. We do have data at this point in time that suggest that it’s probably safe to wait, especially if you have an individual who has perhaps a small number of lesions, who has slowly growing disease, and who has excellent performance status. Especially an individual that really is averse to any type of side effects, we can probably safely watch these individuals. This is a strategy that I certainly employ with some of my patients, and I think the community can be comfortable after having a conversation with a patient, getting an idea of whether or not the patient wants to do that.

Robert A. Figlin, MD: David, let’s zoom in on this concept of active surveillance in kidney cancer, not something that we thought a lot about. Everybody thought over the years, once you find it you treat it, and we’re learning now that that may not be necessary. What are the criteria that you use? Do you use any of the IDMC (The Internal Displacement Monitoring Centre) criteria or Motzer criteria? And how do you decide when a person should or shouldn’t be treated, and then how do you follow such a person over time?

David I. Quinn, MBBS, PhD: We now have some data that helps us. Brian Rini did a study, led from the Cleveland Clinic, that we were involved in where we looked at active surveillance in selected patients. What was clear was that patients who were particularly good-risk—also intermediate-risk based on Motzer criteria or Heng criteria—could do well, especially if they had pulmonary metastases as their major site of disease. I think this provided some surety, for that discussion that we can have with the good-risk patient with pulmonary metastases, to say, “You may not need treatment straight away.” We have another study that’s being presented here at ASCO GU 2017 where active surveillance has been looked at from a different group. They looked at change in tumor burden and chance to progress, and it appears that similar factors predict. So, I think you can talk to a patient who has presented with their first metastatic disease, and the message is that it’s okay to observe them off therapy for a period of time. That will depend on their comfort zone, but they do need to be watched for potential progression. I think it’s important to set up a contingency plan with those patients about what you’re going to do if they progress and we think treatment is needed.

Robert A. Figlin, MD: Other than the lung-dominant, small volume patient, are there categories of patients that you unequivocally would not follow actively without therapy?

David I. Quinn, MBBS, PhD: I would be concerned if they presented with, for example, liver metastases. A solitary brain metastasis that’s treated, I will sometimes follow if there’s no other disease or solitary bone metastasis that’s definitively treated, but they’re riskier groups. I think that is the issue. And I think that’s OK. You just need to talk to the patient. The ones that are difficult for me are the ones that are lymph node predominant. They’ve got a whole bunch of lymph nodes in the back of their abdomen and mediastinum, and they seem to vary a lot. Some of those are fairly quiescent over a long period of time. Others, you wish you had done the next scan earlier because they can progress rapidly. So, it’s not necessarily the conventional group that we thought. If I’m going to give that patient a first-line therapy, I’d like a game changer, so I will talk to them about immunotherapy in the first-line if that’s appropriate for them. Because, while they’ve got these small nodules, if they live long enough based on their other health, they’re going to have issues with this. They may want to try a short period of therapy that changes their outcome with perhaps interleukin-2 or maybe some of the newer immunotherapies that are coming through on trial.

Transcript Edited for Clarity

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Transcript:

Robert A. Figlin, MD:
So, Michael, that gets to a larger conversation around what we consider tolerance to therapy. Maybe what are our goals for treatment, how do we assess quality of life, and how do we integrate that into the approaches that we give? Give us some thoughts in terms of this plethora of agents that we have available, how that plays a role in choosing agents and designing a paradigm for an individual.

Michael R. Harrison, MD: On the topic of tolerance, I think it’s abundantly clear that not all patients tolerate these drugs the same. For the most part, we’re doing flat dosing right off the bat. With the exception of axitinib, there is a dose escalation. A 105-pound woman may tolerate these drugs much differently than a 250-pound man. You did raise the issues of goals of care, and I think that’s a really interesting topic that has been somewhat explored, but we could really go deeper. If you ask patients, “What is your goal?”, different patients have a different balance between prioritizing quality of life versus tumor response variables or outcomes. So, I think it’s important to understand a patient’s goals of care, to understand what therapies you’re putting them on. I certainly think acute supportive care is necessary to manage some of the side effects like diarrhea. But I think one thing we’re realizing is that as patients go into second-, third-, and fourth-line therapy, there are some common themes. One of those is fatigue that’s going across all lines of therapy. And I know we’ve all had patients who have gone through 5 lines of therapy and they wind up in a wheelchair, possibly somewhat from the tumor, but I would also argue from some of the therapies as well. I think we could do better probably with addressing lifestyle changes early on, whether it’s nutritional strategies or exercise strategies, to try to mitigate some of those things like fatigue.

Robert A. Figlin, MD: David, at USC, give me a sense of what the conversation is with the patient now that we have survival data. We’re not talking about either response rate or progression-free survival, endpoints that may be important to the oncologist, but not as important to the patient. How do those conversations go?

David I. Quinn, MBBS, PhD: I think the conversation has evolved recently and fairly significantly. We’ve always had the risk-benefit conversation. What are the risks of you getting side effects that are going to be significant versus us controlling your disease and prolonging your life? We’ve not demonstrated overall survival definitively until very recently with the 2 trials with nivolumab and with cabozantinib. And so, I think it is a different discussion. From that perspective, I think that many patients still get into the paternalistic stuff saying, “Well, look, I’ll take the medication and I really don’t need to have the discussion. Just tell me what I should do.” Throwing the stuff out there to say, “Look, there’s a balance here. We may make you, in some cases, sicker than you really need to be, and the treatment may be worse than the disease,” I think telling them that puts them into a position where you can have that therapeutic discussion. “What’s the balance when we’re seeing you now? We’re controlling your cancer based on the scan and your symptoms from the disease, but what are your side effects and how do we balance that out?”

Robert A. Figlin, MD: Eric, what are your thoughts around when to start? We have this concept now that has been reported of so-called active surveillance. When we know the cancer is there, we know the person has had a distant nephrectomy, the biology of the cancer may be slowing growing. Some people think you should start immediately, some people think you should wait. Where do you come down on that conversation?

Eric Jonasch, MD: There are a couple of abstracts this year at ASCO GU that are addressing that. We do have data at this point in time that suggest that it’s probably safe to wait, especially if you have an individual who has perhaps a small number of lesions, who has slowly growing disease, and who has excellent performance status. Especially an individual that really is averse to any type of side effects, we can probably safely watch these individuals. This is a strategy that I certainly employ with some of my patients, and I think the community can be comfortable after having a conversation with a patient, getting an idea of whether or not the patient wants to do that.

Robert A. Figlin, MD: David, let’s zoom in on this concept of active surveillance in kidney cancer, not something that we thought a lot about. Everybody thought over the years, once you find it you treat it, and we’re learning now that that may not be necessary. What are the criteria that you use? Do you use any of the IDMC (The Internal Displacement Monitoring Centre) criteria or Motzer criteria? And how do you decide when a person should or shouldn’t be treated, and then how do you follow such a person over time?

David I. Quinn, MBBS, PhD: We now have some data that helps us. Brian Rini did a study, led from the Cleveland Clinic, that we were involved in where we looked at active surveillance in selected patients. What was clear was that patients who were particularly good-risk—also intermediate-risk based on Motzer criteria or Heng criteria—could do well, especially if they had pulmonary metastases as their major site of disease. I think this provided some surety, for that discussion that we can have with the good-risk patient with pulmonary metastases, to say, “You may not need treatment straight away.” We have another study that’s being presented here at ASCO GU 2017 where active surveillance has been looked at from a different group. They looked at change in tumor burden and chance to progress, and it appears that similar factors predict. So, I think you can talk to a patient who has presented with their first metastatic disease, and the message is that it’s okay to observe them off therapy for a period of time. That will depend on their comfort zone, but they do need to be watched for potential progression. I think it’s important to set up a contingency plan with those patients about what you’re going to do if they progress and we think treatment is needed.

Robert A. Figlin, MD: Other than the lung-dominant, small volume patient, are there categories of patients that you unequivocally would not follow actively without therapy?

David I. Quinn, MBBS, PhD: I would be concerned if they presented with, for example, liver metastases. A solitary brain metastasis that’s treated, I will sometimes follow if there’s no other disease or solitary bone metastasis that’s definitively treated, but they’re riskier groups. I think that is the issue. And I think that’s OK. You just need to talk to the patient. The ones that are difficult for me are the ones that are lymph node predominant. They’ve got a whole bunch of lymph nodes in the back of their abdomen and mediastinum, and they seem to vary a lot. Some of those are fairly quiescent over a long period of time. Others, you wish you had done the next scan earlier because they can progress rapidly. So, it’s not necessarily the conventional group that we thought. If I’m going to give that patient a first-line therapy, I’d like a game changer, so I will talk to them about immunotherapy in the first-line if that’s appropriate for them. Because, while they’ve got these small nodules, if they live long enough based on their other health, they’re going to have issues with this. They may want to try a short period of therapy that changes their outcome with perhaps interleukin-2 or maybe some of the newer immunotherapies that are coming through on trial.

Transcript Edited for Clarity
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