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Genetic Profiling in HCC

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, Feb 18, 2019



Transcript: 

Ghassan K. Abou-Alfa, MD: Hello, and thank you for joining this OncLive Peer Exchange® titled “Navigating New Treatment Options for Hepatocellular Carcinoma.”

We are experiencing a sea change in terms of systemic therapy for advanced hepatocellular carcinoma [HCC]. In 2019 we have several new options, requiring us to make decisions for both newly diagnosed and relapsed disease. In addition, we are refining the use of liver-directed therapies in earlier-stage HCC. In this OncLive Peer Exchange® panel discussion, we are going to discuss the latest information surrounding the management of advanced liver cancer. We’ll take a detailed look at new opportunities for treatment to provide you with practical perspective on optimal treatment for your patients with HCC.

Today I am joined by a group of my colleagues who are renowned experts in the field of hepatocellular carcinoma research. We will discuss the evolving research presented at the 2019 ASCO GI [Gastrointestinal Cancers Symposium] annual meeting surrounding the treatment of newly diagnosed and relapsed disease, as well as discuss liver-directed therapies for early-stage HCC and the management of advanced-stage disease.

I am Ghassan Abou-Alfa, medical oncologist at Memorial Sloan Kettering Cancer Center and professor of medicine at Weill Medical College at Cornell University in New York, New York.

Participating today on our distinguished panel are:

Dr Richard Finn, professor of medicine in the Department of Medicine, division of hematology and oncology, of the Geffen School of Medicine at UCLA in Los Angeles, California; Dr Kate Kelley, associate professor of clinical medicines in the Department of Hematology and Oncology at the University of California, San Francisco; and Dr Andrew Zhu, professor of medicine at Harvard Medical School and director of Liver Cancer Research and Medicine at Massachusetts General Hospital in Boston, Massachusetts. Thank you so much for joining us. Let’s begin.

Richard, as we saw in the introduction, it admittedly has been an incredible 2 years with regard to liver cancer, but it will be nice to kind of go back to the basics first and really kind of take it from there. At the moment, 1 of the key elements that all of us are seeing in the clinic is patients coming and asking about their genetic profile of their tumor. What does that mean for HCC?

Richard S. Finn, MD: Yeah, so liver cancer, I think, has been the orphan of solid tumor oncology. In many ways, the interventions that are making a difference have generally come to liver cancer as an afterthought. And that is not limited to just therapeutics but also our approach. Still, we approach liver cancer as a one-size-fits-all approach. We don’t differentiate based on molecular makeup, though there have been a lot of molecular studies done. There have been excellent studies from the NCI [National Cancer Institute] and other groups, as well as a large TCGA [The Cancer Genome Atlas]. Just as there’s a TCGA in every other solid tumor, there’s 1 in liver cancer. One of the challenges in liver cancer is that we don’t have a lot of mutations that we have drugs for.

So there’s the challenge of identifying an alteration and saying that we can drug that alteration, and then the other thing is linking that alteration to therapeutic benefit. And right now, as we sit here today, we don’t have a good linkage between molecular diagnostics like Foundation Medicine, for example, and next-generation sequencing leading us to any therapeutic. The 1 exception to that, in all honestly, is something like MSI [microsatellite instable] status. If you found a tumor that’s MSI high, there is a tumor agnostic approval for PD-1 [programmed cell death protein 1] inhibitors in that setting, but that alteration is very rare in liver cancer.

Ghassan K. Abou-Alfa, MD: Fair enough. Actually, I’m going to go back to the story of the checkpoint inhibitors and the genetics. But before we go there, by the way—and to agree with what you said—at this GI ASCO, we saw there was an abstract, if I recall, with regard to the landscape of the germline. However, this really probably doesn’t apply directly to what we are talking about, to hepatobiliary. And there was, in other words, some patients with HCC and other with a biliary tumor, presumably, cholangiocarcinoma. And you’re right, I would say that the data are not yet giving us 1 guidance over the other. Fair enough. Along that line, Katie, 1 of the classic arguments that we hear from our colleagues is you don’t need a biopsy to get a diagnosis of HCC. And ironically, when we hear what Rich said, why do we need a biopsy?

R. Kate Kelley, MD: Increasingly now, we have multiple treatment options, both for HCC and for cholangiocarcinoma. It becomes incumbent upon us before starting a systemic therapy to make sure we’re certain about the radiographic diagnosis, more so than when these cancers were so difficult to treat with limited options. And so, I think increasingly, at least in our institution, what I’m seeing is that before starting systemic therapy we’re pursuing histologic confirmation, in most cases, particularly cases that have equivocal imaging findings, which is not uncommon. So in patients who have an infiltrative tumor without great enhancement in all parts of the tumor, sometimes those can be a mixed HCC, or cholangio, or a frank cholangiocarcinoma, or a surprising histology we weren’t expecting. And so, I think the top priority is making sure we know the right histology before embarking on systemic therapy and to be very rigorous about the cases for which we employ a radiographic diagnosis.

Transcript Edited for Clarity

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Transcript: 

Ghassan K. Abou-Alfa, MD: Hello, and thank you for joining this OncLive Peer Exchange® titled “Navigating New Treatment Options for Hepatocellular Carcinoma.”

We are experiencing a sea change in terms of systemic therapy for advanced hepatocellular carcinoma [HCC]. In 2019 we have several new options, requiring us to make decisions for both newly diagnosed and relapsed disease. In addition, we are refining the use of liver-directed therapies in earlier-stage HCC. In this OncLive Peer Exchange® panel discussion, we are going to discuss the latest information surrounding the management of advanced liver cancer. We’ll take a detailed look at new opportunities for treatment to provide you with practical perspective on optimal treatment for your patients with HCC.

Today I am joined by a group of my colleagues who are renowned experts in the field of hepatocellular carcinoma research. We will discuss the evolving research presented at the 2019 ASCO GI [Gastrointestinal Cancers Symposium] annual meeting surrounding the treatment of newly diagnosed and relapsed disease, as well as discuss liver-directed therapies for early-stage HCC and the management of advanced-stage disease.

I am Ghassan Abou-Alfa, medical oncologist at Memorial Sloan Kettering Cancer Center and professor of medicine at Weill Medical College at Cornell University in New York, New York.

Participating today on our distinguished panel are:

Dr Richard Finn, professor of medicine in the Department of Medicine, division of hematology and oncology, of the Geffen School of Medicine at UCLA in Los Angeles, California; Dr Kate Kelley, associate professor of clinical medicines in the Department of Hematology and Oncology at the University of California, San Francisco; and Dr Andrew Zhu, professor of medicine at Harvard Medical School and director of Liver Cancer Research and Medicine at Massachusetts General Hospital in Boston, Massachusetts. Thank you so much for joining us. Let’s begin.

Richard, as we saw in the introduction, it admittedly has been an incredible 2 years with regard to liver cancer, but it will be nice to kind of go back to the basics first and really kind of take it from there. At the moment, 1 of the key elements that all of us are seeing in the clinic is patients coming and asking about their genetic profile of their tumor. What does that mean for HCC?

Richard S. Finn, MD: Yeah, so liver cancer, I think, has been the orphan of solid tumor oncology. In many ways, the interventions that are making a difference have generally come to liver cancer as an afterthought. And that is not limited to just therapeutics but also our approach. Still, we approach liver cancer as a one-size-fits-all approach. We don’t differentiate based on molecular makeup, though there have been a lot of molecular studies done. There have been excellent studies from the NCI [National Cancer Institute] and other groups, as well as a large TCGA [The Cancer Genome Atlas]. Just as there’s a TCGA in every other solid tumor, there’s 1 in liver cancer. One of the challenges in liver cancer is that we don’t have a lot of mutations that we have drugs for.

So there’s the challenge of identifying an alteration and saying that we can drug that alteration, and then the other thing is linking that alteration to therapeutic benefit. And right now, as we sit here today, we don’t have a good linkage between molecular diagnostics like Foundation Medicine, for example, and next-generation sequencing leading us to any therapeutic. The 1 exception to that, in all honestly, is something like MSI [microsatellite instable] status. If you found a tumor that’s MSI high, there is a tumor agnostic approval for PD-1 [programmed cell death protein 1] inhibitors in that setting, but that alteration is very rare in liver cancer.

Ghassan K. Abou-Alfa, MD: Fair enough. Actually, I’m going to go back to the story of the checkpoint inhibitors and the genetics. But before we go there, by the way—and to agree with what you said—at this GI ASCO, we saw there was an abstract, if I recall, with regard to the landscape of the germline. However, this really probably doesn’t apply directly to what we are talking about, to hepatobiliary. And there was, in other words, some patients with HCC and other with a biliary tumor, presumably, cholangiocarcinoma. And you’re right, I would say that the data are not yet giving us 1 guidance over the other. Fair enough. Along that line, Katie, 1 of the classic arguments that we hear from our colleagues is you don’t need a biopsy to get a diagnosis of HCC. And ironically, when we hear what Rich said, why do we need a biopsy?

R. Kate Kelley, MD: Increasingly now, we have multiple treatment options, both for HCC and for cholangiocarcinoma. It becomes incumbent upon us before starting a systemic therapy to make sure we’re certain about the radiographic diagnosis, more so than when these cancers were so difficult to treat with limited options. And so, I think increasingly, at least in our institution, what I’m seeing is that before starting systemic therapy we’re pursuing histologic confirmation, in most cases, particularly cases that have equivocal imaging findings, which is not uncommon. So in patients who have an infiltrative tumor without great enhancement in all parts of the tumor, sometimes those can be a mixed HCC, or cholangio, or a frank cholangiocarcinoma, or a surprising histology we weren’t expecting. And so, I think the top priority is making sure we know the right histology before embarking on systemic therapy and to be very rigorous about the cases for which we employ a radiographic diagnosis.

Transcript Edited for Clarity
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