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Liver-Directed Therapies in Metastatic Colorectal Cancer

Panelists:Tanios Bekaii-Saab, MD, Ohio State University – James Cancer Hospital; Johanna Bendell, MD, Sarah Cannon Research Institute; Charles S. Fuchs, MD, Dana-Farber Cancer Institute; Richard Kim, MD, Moffitt Cancer Center; John L. Marshall, MD, Georgetown University Hospital
Published: Monday, Feb 29, 2016


Transcript:

John L. Marshall, MD:
Let’s talk a little data. So back to our liver metastatic patient, and the move in liver-directed therapy. Our IR (interventional radiologists) have been there to help us in the refractory setting for a long time with various forms of embolization. The Y90 data, new frontline studies looked at the impact earlier on. Richard, what’s your approach in the liver dominant patient for early liver consolidation?

Richard Kim, MD: There’s data that was presented last year at ASCO, the data using SIR-Spheres in the upfront setting where they included patients with mostly liver dominant disease, but over 40% of the patients did have extrahepatic disease as well. They basically were randomized to chemotherapy plus/minus SIR-Spheres. I think they gave one dose upfront, and that was it. And what they found out was that overall PFS, they did not meet. However, when they looked at the progression-free survival in the liver-only patients, there was a dramatic improvement of up to eight months in the liver only. And that makes sense because you’re using Y90 to attack the liver directly, which I think clearly makes sense.

John L. Marshall, MD: Well, it tells us also that the stuff works.

Richard Kim, MD: Yeah, exactly.

John L. Marshall, MD: Sometimes I wonder if what we’re doing has an impact.

Richard Kim, MD: In our practice, we typically don’t use local therapy upfront for two reasons. Number one is that I’m a little bit concerned about long-term toxicity. So I’m using it as second-line, third-line more than as first-line. And second thing is we don’t have any overall survival data. We know that most of the patients will succumb because of the liver disease, so if this PFS is true, this should translate into overall survival. But that’s the data hopefully will be presented sometime this year or next year.

John L. Marshall, MD: Our IR guys are pretty eager to jump on this and use this early on. I share your concerns about the toxicity. Are there patients where you might say, no, I think you should do this?

Charles S. Fuchs, MD, MPH: I have certainly considered it. The problem with that study is there isn’t an overall PFS benefit. I mean, the liver-specific finding is interesting and encouraging because you hope it works that way, but they don’t have a significant benefit overall on PFS. And so I am curious to see what the survival data are. It’s an important study. I would like to see studies where we figure out how to select the patients as opposed to globally give it to patients. And that really speaks to the question you’re asking me, John, which is, how do you decide who to do it in? And we all have our intuition about what to do. We really need studies.

John L. Marshall, MD: Tony, anybody? I was thinking in big bulky liver disease that responds a little to frontline therapy, maybe you pile on with this kind of approach.

Tanios Bekaii-Saab, MD: I agree with Charlie that unless we see an impact on survival, these numbers look interesting, and it tells us this is a viable option. But, until we see that we’re actually changing the course of the disease by improving survival, at this point of time, I would not recommend this in the first-line in combination with chemotherapy for all the concerns raised.

John L. Marshall, MD: So is this the kind that you send the patient to discuss with IR or you don’t send them?

Johanna Bendell, MD: I am lucky in the sense that our radiation oncologist is actually a pretty big expert in this type of radioembolization approach, and so he does discuss it with the patient and then discuss it back with me. You always worry a little bit sometimes that when you send somebody to a person that does a procedure, they’re going to do the procedure. And you definitely want to be able to have that dialogue. I personally use this, but I use it in later lines of therapy where you have the liver disease dominating the course of how that patient is doing. Because I do believe that you do see a response in the liver and where people ran into trouble in the SIRFLOX study is extrahepatic disease that progressed. And so maybe this is a sign that we need to use this in later lines of therapy.
                                                                                                                                                                                                                                                                                                               
Transcript Edited for Clarity
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Transcript:

John L. Marshall, MD:
Let’s talk a little data. So back to our liver metastatic patient, and the move in liver-directed therapy. Our IR (interventional radiologists) have been there to help us in the refractory setting for a long time with various forms of embolization. The Y90 data, new frontline studies looked at the impact earlier on. Richard, what’s your approach in the liver dominant patient for early liver consolidation?

Richard Kim, MD: There’s data that was presented last year at ASCO, the data using SIR-Spheres in the upfront setting where they included patients with mostly liver dominant disease, but over 40% of the patients did have extrahepatic disease as well. They basically were randomized to chemotherapy plus/minus SIR-Spheres. I think they gave one dose upfront, and that was it. And what they found out was that overall PFS, they did not meet. However, when they looked at the progression-free survival in the liver-only patients, there was a dramatic improvement of up to eight months in the liver only. And that makes sense because you’re using Y90 to attack the liver directly, which I think clearly makes sense.

John L. Marshall, MD: Well, it tells us also that the stuff works.

Richard Kim, MD: Yeah, exactly.

John L. Marshall, MD: Sometimes I wonder if what we’re doing has an impact.

Richard Kim, MD: In our practice, we typically don’t use local therapy upfront for two reasons. Number one is that I’m a little bit concerned about long-term toxicity. So I’m using it as second-line, third-line more than as first-line. And second thing is we don’t have any overall survival data. We know that most of the patients will succumb because of the liver disease, so if this PFS is true, this should translate into overall survival. But that’s the data hopefully will be presented sometime this year or next year.

John L. Marshall, MD: Our IR guys are pretty eager to jump on this and use this early on. I share your concerns about the toxicity. Are there patients where you might say, no, I think you should do this?

Charles S. Fuchs, MD, MPH: I have certainly considered it. The problem with that study is there isn’t an overall PFS benefit. I mean, the liver-specific finding is interesting and encouraging because you hope it works that way, but they don’t have a significant benefit overall on PFS. And so I am curious to see what the survival data are. It’s an important study. I would like to see studies where we figure out how to select the patients as opposed to globally give it to patients. And that really speaks to the question you’re asking me, John, which is, how do you decide who to do it in? And we all have our intuition about what to do. We really need studies.

John L. Marshall, MD: Tony, anybody? I was thinking in big bulky liver disease that responds a little to frontline therapy, maybe you pile on with this kind of approach.

Tanios Bekaii-Saab, MD: I agree with Charlie that unless we see an impact on survival, these numbers look interesting, and it tells us this is a viable option. But, until we see that we’re actually changing the course of the disease by improving survival, at this point of time, I would not recommend this in the first-line in combination with chemotherapy for all the concerns raised.

John L. Marshall, MD: So is this the kind that you send the patient to discuss with IR or you don’t send them?

Johanna Bendell, MD: I am lucky in the sense that our radiation oncologist is actually a pretty big expert in this type of radioembolization approach, and so he does discuss it with the patient and then discuss it back with me. You always worry a little bit sometimes that when you send somebody to a person that does a procedure, they’re going to do the procedure. And you definitely want to be able to have that dialogue. I personally use this, but I use it in later lines of therapy where you have the liver disease dominating the course of how that patient is doing. Because I do believe that you do see a response in the liver and where people ran into trouble in the SIRFLOX study is extrahepatic disease that progressed. And so maybe this is a sign that we need to use this in later lines of therapy.
                                                                                                                                                                                                                                                                                                               
Transcript Edited for Clarity
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