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Understanding Biology and Patient Subsets in HCC

Insights From: Anthony El-Khoueiry, MD, USC Keck School of Medicine; Richard Finn, MD, UCLA Geffen School of Medicine
Published: Friday, Mar 22, 2019



Transcript: 

Richard Finn, MD: Hi, and welcome to this OncLive® News Network webinar. Today’s discussion will be focused on “Novel Approaches to the Treatment of Hepatocellular Carcinoma.” I am your host, Dr. Richard Finn, clinical professor of medicine in the Division of Hematology/Oncology at the David Geffen School of Medicine at UCLA in Los Angeles, California. Today, I am joined by my good friend and colleague, Dr. Anthony El-Khoueiry, associate professor of clinical medicine at the Keck School of Medicine of USC and Norris Cancer Hospital, also in Los Angeles.

During the next 60 minutes, we are going to navigate through some of the questions surrounding how we treat patients with metastatic liver cancer. We’ll consider how we are currently using available agents, how they can be sequenced throughout the disease continuum, and how the latest data will help us in making these decisions in our clinics. During the last few minutes of this broadcast, we will answer questions that have been previously submitted by members of our viewing audience. Let’s get started. Anthony, it’s good to be with you today.

Anthony El-Khoueiry, MD: Thank you.

Richard Finn, MD: In the area of liver cancer, systemic treatment is rapidly changing. If we look back from 2007 to 2017, we only had 1 drug available. Since that time, we’ve seen positive phase III data in both frontline and second-line settings, with increasing approvals in both those areas. For the first part of our broadcast, let’s concentrate on frontline liver cancer. Again, sorafenib has been the established standard of care, and in the past year here in the United States, now globally, lenvatinib has been approved as frontline treatment. Before we talk about specifically triaging those 2 choices, let’s step back and talk about how we approach patients with advanced liver cancer. What does advanced liver cancer mean to you? And when you see a patient, what are some of your considerations?

Anthony El-Khoueiry, MD: Thank you, Richard. Yes, I agree with you, advanced liver cancer tends to be a broad group of patients. So, let’s start from the beginning. These include the patients with liver-limited disease, for example, who have progressed or failed locoregional therapies. That could be chemoembolization, Y-90 [yttrium-90], or other options. So that’s one category. These are the Barcelona Clinic Liver Cancer BCLC-B patients who have failed locoregional therapy. Some of these patients may have actually extensive disease up front such that they may be candidates for systemic therapy directly without going through the locoregional option. If we look at phase III trials for advanced disease, about 20% of the accrual tends to be BCLC-B patients. Then the more traditional understanding of advanced disease are patients with vascular invasion, usually portal vein invasion or extrahepatic metastases. So in short, I just want to emphasize the advanced disease includes a group of BCLC-B patients.

Richard Finn, MD: That’s a lot to consider when approaching the patient. And that also isn’t taking into account the underlying liver dysfunction. How about that? Could you comment? If you have a patient who comes in with a tumor in the liver and the vascular invasion, their bilirubin is maybe 2.5 mg/dL, and their albumin is 3 g/dL, how do you factor that into your assessment of someone for treatment?

Anthony El-Khoueiry, MD: It’s a very important consideration. I frequently tell patients that when we’re treating liver cancer, we’re really ultimately treating 2 diseases: the underlying liver cirrhosis or liver disease, as well as the cancer. To your question, I think frequently patients tend to have some compromise of their underlying liver function. And the patient you mentioned is someone who has slightly elevated bilirubin, slightly low albumin. So, one has to look. Formally, one can calculate the Child-Pugh score, and most of our studies and results come from Child-Pugh A patients because these are the ones who are recruited to phase III trials. We tend to extrapolate and treat Child-Pugh B patients, but usually these are the relatively good Child-Pugh B patients. By good, we mean patients who make it to Child-Pugh B because of slightly elevated bilirubin or low albumin. But patients who have truly decompensated cirrhosis, requiring paracentesis repeatedly, have active encephalopathy, those patients tend to not do well in general, more likely because of their underlying liver cirrhosis rather than their cancer.

Richard Finn, MD: So, is it a problem with safety with the drugs or treatments we use, or is it that their underlying liver dysfunction is going to limit their survival and not their cancer, so to speak?

Anthony El-Khoueiry, MD: Great question. I think, unfortunately, we don’t have adequate safety results for patients with truly decompensated liver cirrhosis. We are starting to get some data about safety of drugs with Child-Pugh B. So, for sorafenib, we have registry data, we have small phase II data for safety in Child-Pugh B, which generally tell us that it’s feasible to treat patients with Child-Pugh B disease. We recently saw data from nivolumab in a Child-Pugh B cohort, but these were patients with B7 and B8 Child-Pugh scores, and they tended to be patients who don’t have active ascites and active encephalopathy.

So, from a safety perspective, there’s potential to treat these patients. But I think the more important discussion is that their prognosis is poorer. Child-Pugh score is a prognostic score, even with active cancer. So, they tend not to do well in general, and it’s a clinical assessment whether these patients are actually going to do worse because of their bad cirrhosis or their cancer and prioritizing these 2 issues and treating accordingly. So, there’s definitely clinical judgment.

Transcript Edited for Clarity
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Transcript: 

Richard Finn, MD: Hi, and welcome to this OncLive® News Network webinar. Today’s discussion will be focused on “Novel Approaches to the Treatment of Hepatocellular Carcinoma.” I am your host, Dr. Richard Finn, clinical professor of medicine in the Division of Hematology/Oncology at the David Geffen School of Medicine at UCLA in Los Angeles, California. Today, I am joined by my good friend and colleague, Dr. Anthony El-Khoueiry, associate professor of clinical medicine at the Keck School of Medicine of USC and Norris Cancer Hospital, also in Los Angeles.

During the next 60 minutes, we are going to navigate through some of the questions surrounding how we treat patients with metastatic liver cancer. We’ll consider how we are currently using available agents, how they can be sequenced throughout the disease continuum, and how the latest data will help us in making these decisions in our clinics. During the last few minutes of this broadcast, we will answer questions that have been previously submitted by members of our viewing audience. Let’s get started. Anthony, it’s good to be with you today.

Anthony El-Khoueiry, MD: Thank you.

Richard Finn, MD: In the area of liver cancer, systemic treatment is rapidly changing. If we look back from 2007 to 2017, we only had 1 drug available. Since that time, we’ve seen positive phase III data in both frontline and second-line settings, with increasing approvals in both those areas. For the first part of our broadcast, let’s concentrate on frontline liver cancer. Again, sorafenib has been the established standard of care, and in the past year here in the United States, now globally, lenvatinib has been approved as frontline treatment. Before we talk about specifically triaging those 2 choices, let’s step back and talk about how we approach patients with advanced liver cancer. What does advanced liver cancer mean to you? And when you see a patient, what are some of your considerations?

Anthony El-Khoueiry, MD: Thank you, Richard. Yes, I agree with you, advanced liver cancer tends to be a broad group of patients. So, let’s start from the beginning. These include the patients with liver-limited disease, for example, who have progressed or failed locoregional therapies. That could be chemoembolization, Y-90 [yttrium-90], or other options. So that’s one category. These are the Barcelona Clinic Liver Cancer BCLC-B patients who have failed locoregional therapy. Some of these patients may have actually extensive disease up front such that they may be candidates for systemic therapy directly without going through the locoregional option. If we look at phase III trials for advanced disease, about 20% of the accrual tends to be BCLC-B patients. Then the more traditional understanding of advanced disease are patients with vascular invasion, usually portal vein invasion or extrahepatic metastases. So in short, I just want to emphasize the advanced disease includes a group of BCLC-B patients.

Richard Finn, MD: That’s a lot to consider when approaching the patient. And that also isn’t taking into account the underlying liver dysfunction. How about that? Could you comment? If you have a patient who comes in with a tumor in the liver and the vascular invasion, their bilirubin is maybe 2.5 mg/dL, and their albumin is 3 g/dL, how do you factor that into your assessment of someone for treatment?

Anthony El-Khoueiry, MD: It’s a very important consideration. I frequently tell patients that when we’re treating liver cancer, we’re really ultimately treating 2 diseases: the underlying liver cirrhosis or liver disease, as well as the cancer. To your question, I think frequently patients tend to have some compromise of their underlying liver function. And the patient you mentioned is someone who has slightly elevated bilirubin, slightly low albumin. So, one has to look. Formally, one can calculate the Child-Pugh score, and most of our studies and results come from Child-Pugh A patients because these are the ones who are recruited to phase III trials. We tend to extrapolate and treat Child-Pugh B patients, but usually these are the relatively good Child-Pugh B patients. By good, we mean patients who make it to Child-Pugh B because of slightly elevated bilirubin or low albumin. But patients who have truly decompensated cirrhosis, requiring paracentesis repeatedly, have active encephalopathy, those patients tend to not do well in general, more likely because of their underlying liver cirrhosis rather than their cancer.

Richard Finn, MD: So, is it a problem with safety with the drugs or treatments we use, or is it that their underlying liver dysfunction is going to limit their survival and not their cancer, so to speak?

Anthony El-Khoueiry, MD: Great question. I think, unfortunately, we don’t have adequate safety results for patients with truly decompensated liver cirrhosis. We are starting to get some data about safety of drugs with Child-Pugh B. So, for sorafenib, we have registry data, we have small phase II data for safety in Child-Pugh B, which generally tell us that it’s feasible to treat patients with Child-Pugh B disease. We recently saw data from nivolumab in a Child-Pugh B cohort, but these were patients with B7 and B8 Child-Pugh scores, and they tended to be patients who don’t have active ascites and active encephalopathy.

So, from a safety perspective, there’s potential to treat these patients. But I think the more important discussion is that their prognosis is poorer. Child-Pugh score is a prognostic score, even with active cancer. So, they tend not to do well in general, and it’s a clinical assessment whether these patients are actually going to do worse because of their bad cirrhosis or their cancer and prioritizing these 2 issues and treating accordingly. So, there’s definitely clinical judgment.

Transcript Edited for Clarity
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