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Metastatic RCC: Decision Trees for Second-Line Therapy

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, Apr 05, 2017



Transcript:

Robert A. Figlin, MD:
So, what it seems like—and I’d like my colleagues to weigh in—is you are, in part, making decisions on past history. How did Mrs. Jones do in her prior therapies? You’re, in part, making decisions based upon current functional status and trying to be a bit provocative. You’re then making decisions on some subset analyses from prospective trials and using those subset analyses to identify patient populations that might benefit from one approach versus the other. And I don’t want to put words in your mouth, and certainly we all do this, but there is a bit of a paucity of data to help us compare many of the decision-making trees that we have around choosing treatment A, B, C, or D when they’re all basically approved in the second-line setting. They’ve never been compared in the second-line setting, and yet each one is trying to demonstrate its use and demonstrate to others why theirs is the preferred treatment in the second-line setting. David, you’re the honest broker, help us figure that out.

David I. Quinn, MBBS, PhD: Well, I think what you said about a paucity of data and what we choose to believe is very important. I think we’re moving forward the best we can in terms of selection. So, for example, if it had said that we have a patient who’s on their first VEGF TKI, it could be first- or second-line, and they go more than 180 days, there’s a subsequent benefit to a further VEGF TKI. But that comes from a study where we looked at sequential sunitinib and sorafenib/temsirolimus, and is also supported to some extent by the results from the AXIS study, where axitinib in those patients who had more than 180 days of sunitinib first-line did well. Beyond that, the rest is our balance of what we choose to believe, and it is difficult. We have beliefs about tempo of disease. Some people will say the patient is growing rapidly after pazopanib or on the back end of sunitinib or pazopanib. I really feel like I should give a VEGF TKI, which would be cabozantinib, rather than an immunotherapy because I think I’ll get a more rapid response. The evidence doesn’t actually support that. We have no comparative evidence. But the responses to immunotherapy and cabozantinib are relatively quick, and you end up with an issue of working out what the benefit is going to be.

The other issue is related to the comorbidities that a patient brings to the table. Most of my patients in the second-line setting, I’m going to give them nivolumab because it’s well-tolerated and I think they want to break from VEGF toxicities. But cabozantinib is a great drug. It’s probably our best VEGF TKI inhibitor. Plus I tend to reserve that for a group of patients that are bad actors. They have organ transplants. They have autoimmune disease or something else that’s going to make me not want to give an immunotherapy. So, from that perspective, I’m selecting out those bad-actor patients to put on a drug where I might have considered there was variable tolerability, there was some toxicity. In fact, they’ve handled it quite well and I’ve been surprised at how well they’ve done. There are some issues with what comorbidities the patients bring to the table. And then, we’ve got oral and intravenous administration, which doesn’t really alter my selection. Although, you do have some patients that don’t want to come to the clinic every 2 weeks and are happy at taking a pill, and trying to correspond by distance and telephone.

Transcript Edited for Clarity

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Transcript:

Robert A. Figlin, MD:
So, what it seems like—and I’d like my colleagues to weigh in—is you are, in part, making decisions on past history. How did Mrs. Jones do in her prior therapies? You’re, in part, making decisions based upon current functional status and trying to be a bit provocative. You’re then making decisions on some subset analyses from prospective trials and using those subset analyses to identify patient populations that might benefit from one approach versus the other. And I don’t want to put words in your mouth, and certainly we all do this, but there is a bit of a paucity of data to help us compare many of the decision-making trees that we have around choosing treatment A, B, C, or D when they’re all basically approved in the second-line setting. They’ve never been compared in the second-line setting, and yet each one is trying to demonstrate its use and demonstrate to others why theirs is the preferred treatment in the second-line setting. David, you’re the honest broker, help us figure that out.

David I. Quinn, MBBS, PhD: Well, I think what you said about a paucity of data and what we choose to believe is very important. I think we’re moving forward the best we can in terms of selection. So, for example, if it had said that we have a patient who’s on their first VEGF TKI, it could be first- or second-line, and they go more than 180 days, there’s a subsequent benefit to a further VEGF TKI. But that comes from a study where we looked at sequential sunitinib and sorafenib/temsirolimus, and is also supported to some extent by the results from the AXIS study, where axitinib in those patients who had more than 180 days of sunitinib first-line did well. Beyond that, the rest is our balance of what we choose to believe, and it is difficult. We have beliefs about tempo of disease. Some people will say the patient is growing rapidly after pazopanib or on the back end of sunitinib or pazopanib. I really feel like I should give a VEGF TKI, which would be cabozantinib, rather than an immunotherapy because I think I’ll get a more rapid response. The evidence doesn’t actually support that. We have no comparative evidence. But the responses to immunotherapy and cabozantinib are relatively quick, and you end up with an issue of working out what the benefit is going to be.

The other issue is related to the comorbidities that a patient brings to the table. Most of my patients in the second-line setting, I’m going to give them nivolumab because it’s well-tolerated and I think they want to break from VEGF toxicities. But cabozantinib is a great drug. It’s probably our best VEGF TKI inhibitor. Plus I tend to reserve that for a group of patients that are bad actors. They have organ transplants. They have autoimmune disease or something else that’s going to make me not want to give an immunotherapy. So, from that perspective, I’m selecting out those bad-actor patients to put on a drug where I might have considered there was variable tolerability, there was some toxicity. In fact, they’ve handled it quite well and I’ve been surprised at how well they’ve done. There are some issues with what comorbidities the patients bring to the table. And then, we’ve got oral and intravenous administration, which doesn’t really alter my selection. Although, you do have some patients that don’t want to come to the clinic every 2 weeks and are happy at taking a pill, and trying to correspond by distance and telephone.

Transcript Edited for Clarity
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