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HCC: Timing of Locoregional and Systemic Therapies

Panelists: Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center; Richard S. Finn, MD, UCLA; Laura M. Kulik, MD, Northwestern University Feinberg School of Medicine; R. Kate Kelley, MD, University of California-San Francisco; Riad Salem, MD, Northwestern University Feinberg School of Medicine
Published: Thursday, Mar 02, 2017



Transcript:

Ghassan K. Abou-Alfa, MD:
What we just heard, Riad, is a little bit of that collusion, pushing some of the BCLC (Barcelona clinic liver cancer) criteria into an early start with systemic therapy because of the concern from medical oncologists’ view. What about what we hear about the application of the local therapies into more BCLC signatures?

Riad Salem, MD: In reality, I don’t know that it’s that much of a debate. We actually agree. We think there is a healthy medium and healthy balance between the locoregional therapy and the systemic chemotherapy. We agree that we want to be cautious to make sure that we perform treatment selectively and maintain liver function. We agree that we want to make sure to start systemic therapy early and not wait for progression. In fact, this is work that we did years ago, showing that you want to start systemic therapy soon after locoregional therapy, not wait for progression. Because if you wait for progression, then half of those patients have decompensated liver disease, and we studied this in fine detail. So, I actually agree with that. I believe in using locoregional therapy and then early use of systemic therapy. This is part of the individualization. This is part of experience. It’s not explicitly stated in guidelines, but we are, at least at Northwestern, on our 1000th HCC patient coming up this week treated with Y-90. I think in other locoregional therapies, we have pretty much figured out that, again, like Richard was saying, early use of systemic therapies is really the way to go after 1 or 2 rounds of locoregional therapy. So, we agree.

Ghassan K. Abou-Alfa, MD: And do you think there is a potential for or an interest in seeing a local therapy applied in a systemic situation, maybe in combination with systemic therapy?

Riad Salem, MD: Yes. That’s a great question. One of the areas that has been really traditionally developed and considered a niche application for Y-90 is the BCLCC patient that has portal vein thrombosis (PVT), BCLC criteria because of the PVT. And Laura was saying, in terms of the microembolic effect, you can use yttrium-90 as a cytotoxic without risk of ischemic hepatitis. And we do believe, in the early adjuvant use of something like sorafenib, and some of our best results are like this. We’ve got some patients converted to surgery, and the people are really pushing these concepts. So, we’ve seen this with the locoregional therapy, particularly yttrium-90, the use of early sorafenib. And now with regorafenib data, it will be interesting to see how we incorporate that. But we’ve been on that. I’ve agreed to that for several years. In fact, that’s how we’ve practiced.

Ghassan K. Abou-Alfa, MD: Can you tell us a little bit more about studies, like the SARAH study, and where does it fit?

Riad Salem, MD: There has been a lot of interest, although a lot of difficulty, in executing, in performing head-to-head studies. It’s very difficult to compare a therapy, an intervention with a drug. The SARAH study is a head-to-head analysis comparing Y-90 to sorafenib, and the study has enrolled. I believe it will be reporting this year. We’re very excited to see what the results are. Some of the issues that might arise are what the inclusion criteria were. Because as we’ve learned in HCC, clinical trial design is critical, patient selection is critical. There are a lot of negative studies out there, potentially because of incorrect patient selection criteria. But we’ll be interested to see how that is. The limitation I fear with these head-to-head studies is overall survival as an endpoint will be confounded by crossover and posttreatment progression and posttreatment therapies, such as now, regorafenib. So, I fear that while the study is robustly performed, some patients will go crossover, some will get regorafenib, and then we’ll have to interpret these data. But this is a reality of doing HCC studies.

Ghassan K. Abou-Alfa, MD: Very fascinating. If anything, to summarize, local therapy took a very quick improvement in regard to the research and development, and we just heard from the world expert on yttrium-90. But the same thing applies for TACE and TAE. Obviously, there is a better understanding of where do they apply and what’s the value in regard to their benefit for patients. Nonetheless, it remains a rather debatable field because of the advancement, or rapid advancement, in regard to the different technologies and also where each one of them might fit at the end of the day. We probably all agree, and we just stated it that passing the information to the patient and consult early in the game with an interventional radiologist are very critical to assure that they have the applicable local therapy as being necessary. We also heard what we talk about in the academic world about the collusion between the local and systemic therapy. But you probably noticed, as much as I tried to create a debate over here, there is a clear agreement that it’s going to be more of a marriage rather than a separation of the 2 therapies.

Transcript Edited for Clarity

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Transcript:

Ghassan K. Abou-Alfa, MD:
What we just heard, Riad, is a little bit of that collusion, pushing some of the BCLC (Barcelona clinic liver cancer) criteria into an early start with systemic therapy because of the concern from medical oncologists’ view. What about what we hear about the application of the local therapies into more BCLC signatures?

Riad Salem, MD: In reality, I don’t know that it’s that much of a debate. We actually agree. We think there is a healthy medium and healthy balance between the locoregional therapy and the systemic chemotherapy. We agree that we want to be cautious to make sure that we perform treatment selectively and maintain liver function. We agree that we want to make sure to start systemic therapy early and not wait for progression. In fact, this is work that we did years ago, showing that you want to start systemic therapy soon after locoregional therapy, not wait for progression. Because if you wait for progression, then half of those patients have decompensated liver disease, and we studied this in fine detail. So, I actually agree with that. I believe in using locoregional therapy and then early use of systemic therapy. This is part of the individualization. This is part of experience. It’s not explicitly stated in guidelines, but we are, at least at Northwestern, on our 1000th HCC patient coming up this week treated with Y-90. I think in other locoregional therapies, we have pretty much figured out that, again, like Richard was saying, early use of systemic therapies is really the way to go after 1 or 2 rounds of locoregional therapy. So, we agree.

Ghassan K. Abou-Alfa, MD: And do you think there is a potential for or an interest in seeing a local therapy applied in a systemic situation, maybe in combination with systemic therapy?

Riad Salem, MD: Yes. That’s a great question. One of the areas that has been really traditionally developed and considered a niche application for Y-90 is the BCLCC patient that has portal vein thrombosis (PVT), BCLC criteria because of the PVT. And Laura was saying, in terms of the microembolic effect, you can use yttrium-90 as a cytotoxic without risk of ischemic hepatitis. And we do believe, in the early adjuvant use of something like sorafenib, and some of our best results are like this. We’ve got some patients converted to surgery, and the people are really pushing these concepts. So, we’ve seen this with the locoregional therapy, particularly yttrium-90, the use of early sorafenib. And now with regorafenib data, it will be interesting to see how we incorporate that. But we’ve been on that. I’ve agreed to that for several years. In fact, that’s how we’ve practiced.

Ghassan K. Abou-Alfa, MD: Can you tell us a little bit more about studies, like the SARAH study, and where does it fit?

Riad Salem, MD: There has been a lot of interest, although a lot of difficulty, in executing, in performing head-to-head studies. It’s very difficult to compare a therapy, an intervention with a drug. The SARAH study is a head-to-head analysis comparing Y-90 to sorafenib, and the study has enrolled. I believe it will be reporting this year. We’re very excited to see what the results are. Some of the issues that might arise are what the inclusion criteria were. Because as we’ve learned in HCC, clinical trial design is critical, patient selection is critical. There are a lot of negative studies out there, potentially because of incorrect patient selection criteria. But we’ll be interested to see how that is. The limitation I fear with these head-to-head studies is overall survival as an endpoint will be confounded by crossover and posttreatment progression and posttreatment therapies, such as now, regorafenib. So, I fear that while the study is robustly performed, some patients will go crossover, some will get regorafenib, and then we’ll have to interpret these data. But this is a reality of doing HCC studies.

Ghassan K. Abou-Alfa, MD: Very fascinating. If anything, to summarize, local therapy took a very quick improvement in regard to the research and development, and we just heard from the world expert on yttrium-90. But the same thing applies for TACE and TAE. Obviously, there is a better understanding of where do they apply and what’s the value in regard to their benefit for patients. Nonetheless, it remains a rather debatable field because of the advancement, or rapid advancement, in regard to the different technologies and also where each one of them might fit at the end of the day. We probably all agree, and we just stated it that passing the information to the patient and consult early in the game with an interventional radiologist are very critical to assure that they have the applicable local therapy as being necessary. We also heard what we talk about in the academic world about the collusion between the local and systemic therapy. But you probably noticed, as much as I tried to create a debate over here, there is a clear agreement that it’s going to be more of a marriage rather than a separation of the 2 therapies.

Transcript Edited for Clarity
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