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Advanced HCC: What's Next?

Panelists: Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center; Richard S. Finn, MD, University of California Los Angeles; R. Kate Kelley, MD, University of California San Francisco; Andrew X. Zhu, MD, PhD, Harvard Medical School; Tony Saab, MD, Mayo Clinic
Published: Monday, Apr 01, 2019



Transcript: 

Ghassan K. Abou-Alfa, MD: I would like to end our very valuable discussion here by asking each one of you about—all right, great, out of nothing we moved in the speed of light. I’m not sure even if there is any other disease that we’re able to move from 1 drug to 7 in barely a few years. And the question is, we’re going to work on trying to line them up or what have we, but I’d like to hear just kind of [what] your feel is. Where are we going to go next? Or what do you think, what is exciting you for the future now at the moment? Katie?

R. Kate Kelley, MD: I think now that we have more tools at our disposal to help our patients live longer. [That] has been a top priority in the past decade and certainly the predominant part of my career so far. Now I think it’s time to step back and to really try to refine our understanding of the biology of this incredibly heterogeneous patient population. Because we know that some of these drugs have remarkable efficacy in subsets. Lenvatinib with its high response rate or the checkpoint inhibitors with their incredibly durable responses. And certainly TKIs [tyrosine kinase inhibitors] and sequencing TKIs with the long survival that we can see now with multiple agents available. I think it’s incumbent upon us to really try to refine the biomarkers and the populations, whether [they’re] clinical biomarkers or preferably the noninvasive, but whatever we can do to really understand which patients respond to which strategies.

Ghassan K. Abou-Alfa, MD: Fair enough. Rich?

Richard S. Finn, MD: I mean certainly it’s exciting to see this new combination of biologics all moving to front line. You know if these hold up – lenalidomide, pembrolizumab, bevacizumab, atezolizumab – with response rates of 30%, and those are as durable as we’ve seen maybe with the single agents, that’s very exciting. Right? But ultimately 1 of the messages I think we need to leave our audience is the only way we’re going to get patients to benefit from these drugs, if they’re physically in condition to be treated, right? And that means being involved in patients with their liver cancer, even earlier liver cancer. [For] patients who are being seen by the interventional radiologist, whether you’re a hepatologist, [a] gastroenterologist, or [an] oncologist, you have to keep in mind that liver cancer is no longer a 1-drug disease. And that in order to get benefits from these, we need to probably not do that extra TACE if it’s not indicated. Meaning, if patients have stage migrated.

Ghassan K. Abou-Alfa, MD: Fair enough. And Andrew, your thoughts.

Andrew X. Zhu, MD, PhD: So this is a very exciting time for all of us. But I think, you know, we should not be content with having 7 drugs. I still think we should actually continue to explore what’s actually the additional driver, additional new drugs that we can actually evaluate this disease.

And second, I do think the combination strategy present a lot of [challenges] for all of us. Perhaps we should actually try to move from the empiric combination strategy to some more rational designed combination so that we can actually properly improve the success of some of the ongoing combination strategies. And lastly, I do concur with what’s been said. This is a very heterogeneous disease. We’re trying to define them clinically. We’re doing a little better, but we have to really apply all the updated molecular genomic technology to really stratify our patients on how each subgroup will benefit from certain [drugs]. If we do better, I think when the patient [walks] into the clinic, we can definitely advise them better. But also you know give them the maximal benefit and spare them from unnecessary safety toxicity profile.

Ghassan K. Abou-Alfa, MD: I like very much what they said, what I heard. If anything, we understood that there was quite a bit of intrigue and interest in regard to the heterogeneity of the disease. And actually to that matter, there’s quite a bit of activity currently going on in multiple trials. As an example, 1 of the things that we’re doing at [Memorial] Sloan Kettering [Cancer Center] is actually looking at tumor cohorts of ATC [anaplastic thyroid carcinoma] from literally all over the world. At the moment we have 26 countries involved, and we’re doing a DNA, RNA, and 14 analyses of all them.

The other thing that we heard, which really—I totally agree with Rich—is in regard to the understanding about the applicability of local therapy versus systemic, and where does this fine line in regard to the application of what the local therapy will apply in the, what we call “BCLC-B” and in regard to systemic therapy with the BCLC-C, and this definitely is something to we are going to continue to work on.

And I like very much what Andrew said. And if anything, always I admire Andrew for his energy. And I totally agree that we should not satisfy ourselves with 7 drugs. We still have like a long way to go. And among which, for example, something that is exciting is quite a bit at the moment is actually CAR-T [chimeric antigen receptor T-cell therapy] and definitely this will be a very intriguing asset to look into further in regard to ACC [adrenocortical carcinoma].

I thank you all for your contributions to the discussion. On behalf of the panel, we thank you for joining us, and we hope you found this Peer Exchange discussion be useful and informative.

Transcript Edited for Clarity

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Transcript: 

Ghassan K. Abou-Alfa, MD: I would like to end our very valuable discussion here by asking each one of you about—all right, great, out of nothing we moved in the speed of light. I’m not sure even if there is any other disease that we’re able to move from 1 drug to 7 in barely a few years. And the question is, we’re going to work on trying to line them up or what have we, but I’d like to hear just kind of [what] your feel is. Where are we going to go next? Or what do you think, what is exciting you for the future now at the moment? Katie?

R. Kate Kelley, MD: I think now that we have more tools at our disposal to help our patients live longer. [That] has been a top priority in the past decade and certainly the predominant part of my career so far. Now I think it’s time to step back and to really try to refine our understanding of the biology of this incredibly heterogeneous patient population. Because we know that some of these drugs have remarkable efficacy in subsets. Lenvatinib with its high response rate or the checkpoint inhibitors with their incredibly durable responses. And certainly TKIs [tyrosine kinase inhibitors] and sequencing TKIs with the long survival that we can see now with multiple agents available. I think it’s incumbent upon us to really try to refine the biomarkers and the populations, whether [they’re] clinical biomarkers or preferably the noninvasive, but whatever we can do to really understand which patients respond to which strategies.

Ghassan K. Abou-Alfa, MD: Fair enough. Rich?

Richard S. Finn, MD: I mean certainly it’s exciting to see this new combination of biologics all moving to front line. You know if these hold up – lenalidomide, pembrolizumab, bevacizumab, atezolizumab – with response rates of 30%, and those are as durable as we’ve seen maybe with the single agents, that’s very exciting. Right? But ultimately 1 of the messages I think we need to leave our audience is the only way we’re going to get patients to benefit from these drugs, if they’re physically in condition to be treated, right? And that means being involved in patients with their liver cancer, even earlier liver cancer. [For] patients who are being seen by the interventional radiologist, whether you’re a hepatologist, [a] gastroenterologist, or [an] oncologist, you have to keep in mind that liver cancer is no longer a 1-drug disease. And that in order to get benefits from these, we need to probably not do that extra TACE if it’s not indicated. Meaning, if patients have stage migrated.

Ghassan K. Abou-Alfa, MD: Fair enough. And Andrew, your thoughts.

Andrew X. Zhu, MD, PhD: So this is a very exciting time for all of us. But I think, you know, we should not be content with having 7 drugs. I still think we should actually continue to explore what’s actually the additional driver, additional new drugs that we can actually evaluate this disease.

And second, I do think the combination strategy present a lot of [challenges] for all of us. Perhaps we should actually try to move from the empiric combination strategy to some more rational designed combination so that we can actually properly improve the success of some of the ongoing combination strategies. And lastly, I do concur with what’s been said. This is a very heterogeneous disease. We’re trying to define them clinically. We’re doing a little better, but we have to really apply all the updated molecular genomic technology to really stratify our patients on how each subgroup will benefit from certain [drugs]. If we do better, I think when the patient [walks] into the clinic, we can definitely advise them better. But also you know give them the maximal benefit and spare them from unnecessary safety toxicity profile.

Ghassan K. Abou-Alfa, MD: I like very much what they said, what I heard. If anything, we understood that there was quite a bit of intrigue and interest in regard to the heterogeneity of the disease. And actually to that matter, there’s quite a bit of activity currently going on in multiple trials. As an example, 1 of the things that we’re doing at [Memorial] Sloan Kettering [Cancer Center] is actually looking at tumor cohorts of ATC [anaplastic thyroid carcinoma] from literally all over the world. At the moment we have 26 countries involved, and we’re doing a DNA, RNA, and 14 analyses of all them.

The other thing that we heard, which really—I totally agree with Rich—is in regard to the understanding about the applicability of local therapy versus systemic, and where does this fine line in regard to the application of what the local therapy will apply in the, what we call “BCLC-B” and in regard to systemic therapy with the BCLC-C, and this definitely is something to we are going to continue to work on.

And I like very much what Andrew said. And if anything, always I admire Andrew for his energy. And I totally agree that we should not satisfy ourselves with 7 drugs. We still have like a long way to go. And among which, for example, something that is exciting is quite a bit at the moment is actually CAR-T [chimeric antigen receptor T-cell therapy] and definitely this will be a very intriguing asset to look into further in regard to ACC [adrenocortical carcinoma].

I thank you all for your contributions to the discussion. On behalf of the panel, we thank you for joining us, and we hope you found this Peer Exchange discussion be useful and informative.

Transcript Edited for Clarity
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