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Treatment Options for Locally Advanced 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: Tuesday, Feb 26, 2019



Transcript: 

Ghassan K. Abou-Alfa, MD: To go back and to carry on from what Andrew said, Katie, a patient has very early-stage disease, 1 of the key elements that come into play. And you guys at UCSF [University of California, San Francisco] really are especially high up in the game with regard to transplant. Surgery versus transplant for early disease. Tell us a little bit more.

R. Kate Kelley, MD: That’s a great question. There’s not always an absolute answer 1 way or the other. But this returns exactly to the point you were just discussing of, what is the underlying liver function? Surgical candidacy depends on tumor anatomic factors. How large is the tumor? How close is it to other vital structures? Can it be physically removed with the remnant liver intact, and functional? And what is the function of that leftover parenchyma? In patients with small tumors within the ability to be completely resected safely, generally transplantation is favored. But if patients have underlying cirrhosis in unhealthy remnants, transplant is an option that may help them have a curative outcome similar to surgery and also replace the diseased liver at the same time.

Ghassan K. Abou-Alfa, MD: Sure, sure. And, understandably. I would say that maybe the resection versus transplant is mainly driven by liver functionality, even though you’re right, it could be argued versus or against.

R. Kate Kelley, MD: Absolutely.

Ghassan K. Abou-Alfa, MD: Fair enough. We move on from the curative intent, and I think we add to this our phase I. And let’s move a little bit to a more indiscretion at the moment, the local disease. Rich, for locally advanced disease that we cannot technically cure, what are the options?

Richard S. Finn, MD: Certainly, this disease is very complex, and I think we’ve established that. It’s liver disease; it’s malignancy; there’s a role for surgery, interventional radiology. And I think it’s very important that patients are assessed at a large center, because the rules for transplant and resection—they’re changing rapidly. But the population that you’re talking about are patients who have a tumor burden that’s confined to the liver. It probably is not spread outside the liver and probably is not invading into the vasculature of the liver by the Barcelona Clinic Liver Cancer criteria, or BCLC. We’re talking about the B population, and this is a group of patients who are unresectable because of the tumor burden. The liver function is still preserved. It could be A or B, and these are patients who have clearly gotten a benefit from a locoregional treatment like chemoembolization.

Ghassan K. Abou-Alfa, MD: Sure. And along that line with the chemoembolization, Andrew, we saw at this meeting, at GI ASCO 2019 [Gastrointestinal Cancers Symposium], Dr Ahmed Kaseb from The University of Texas MD Anderson Cancer Center, our colleague, present some quite intriguing data with regard to perioperative, and he called it a perioperative phase II of nivolumab alone versus nivo plus ipi [ipilimumab] in patients with a resectable HCC. They went for surgery, and then they followed after that on the treatment, per se. And if I do recall, and I’m reading it here as we speak, the point that really impressed them the most was that there was—because, of course, they treated their resection, so they have the tissue—a complete response of 37.5%, with regard to the pretreated patients who got to the resection, per se. I know that there’s quite a bit of intrigue about checkpoint inhibitors with regard to adjuvant therapy, and you’ve been heavily involved in that arena. So what do you make out of this perioperative use of checkpoint inhibitors prior to surgery and with those results that I mentioned with the complete response?

Andrew X. Zhu, MD, PhD: Yeah. I think, Ghassan, this is a very intriguing and innovative approach, in my opinion. I think we’ve been gaining most of the experience of PD-1 [programmed cell death protein 1]–like molecules in the advanced stage. We know the drug is probably working in about 15% to 20% of the patient population. We have a very, very limited understanding of why this drug works in the selected population. We have actually tried to improve the outcome in the adjuvant setting with the targeted agents over the years and without any success. So I think with the emerging data of the checkpoint inhibitor in the advanced stage, I think 1 natural question is, can you move these drugs earlier? And also, more importantly, what is the drug actually doing to the tumor microenvironment, both to the tumor as well as the surrounding liver?

So you can imagine if you have a perioperative approach in a very well-conducted small study, you can actually address those questions. You actually have the luxury of looking at patients who are getting exposed to the drug and look at the surgical specimen. So I think mechanistically it’s a very, very interesting study. On the practical side, you can look at how this is actually going to be incorporated into the adjuvant or neoadjuvant setting, and there’s no doubt in my mind right now we’re not quite there yet. We have to see how the data is evolving in the adjuvant setting. I think to move directly to the neoadjuvant setting, I think we’re not quite there yet. But I think as an exploratory study, to look at the potential mechanism of action of this class of agents, I think this is a very innovative approach.

Transcript Edited for Clarity

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Transcript: 

Ghassan K. Abou-Alfa, MD: To go back and to carry on from what Andrew said, Katie, a patient has very early-stage disease, 1 of the key elements that come into play. And you guys at UCSF [University of California, San Francisco] really are especially high up in the game with regard to transplant. Surgery versus transplant for early disease. Tell us a little bit more.

R. Kate Kelley, MD: That’s a great question. There’s not always an absolute answer 1 way or the other. But this returns exactly to the point you were just discussing of, what is the underlying liver function? Surgical candidacy depends on tumor anatomic factors. How large is the tumor? How close is it to other vital structures? Can it be physically removed with the remnant liver intact, and functional? And what is the function of that leftover parenchyma? In patients with small tumors within the ability to be completely resected safely, generally transplantation is favored. But if patients have underlying cirrhosis in unhealthy remnants, transplant is an option that may help them have a curative outcome similar to surgery and also replace the diseased liver at the same time.

Ghassan K. Abou-Alfa, MD: Sure, sure. And, understandably. I would say that maybe the resection versus transplant is mainly driven by liver functionality, even though you’re right, it could be argued versus or against.

R. Kate Kelley, MD: Absolutely.

Ghassan K. Abou-Alfa, MD: Fair enough. We move on from the curative intent, and I think we add to this our phase I. And let’s move a little bit to a more indiscretion at the moment, the local disease. Rich, for locally advanced disease that we cannot technically cure, what are the options?

Richard S. Finn, MD: Certainly, this disease is very complex, and I think we’ve established that. It’s liver disease; it’s malignancy; there’s a role for surgery, interventional radiology. And I think it’s very important that patients are assessed at a large center, because the rules for transplant and resection—they’re changing rapidly. But the population that you’re talking about are patients who have a tumor burden that’s confined to the liver. It probably is not spread outside the liver and probably is not invading into the vasculature of the liver by the Barcelona Clinic Liver Cancer criteria, or BCLC. We’re talking about the B population, and this is a group of patients who are unresectable because of the tumor burden. The liver function is still preserved. It could be A or B, and these are patients who have clearly gotten a benefit from a locoregional treatment like chemoembolization.

Ghassan K. Abou-Alfa, MD: Sure. And along that line with the chemoembolization, Andrew, we saw at this meeting, at GI ASCO 2019 [Gastrointestinal Cancers Symposium], Dr Ahmed Kaseb from The University of Texas MD Anderson Cancer Center, our colleague, present some quite intriguing data with regard to perioperative, and he called it a perioperative phase II of nivolumab alone versus nivo plus ipi [ipilimumab] in patients with a resectable HCC. They went for surgery, and then they followed after that on the treatment, per se. And if I do recall, and I’m reading it here as we speak, the point that really impressed them the most was that there was—because, of course, they treated their resection, so they have the tissue—a complete response of 37.5%, with regard to the pretreated patients who got to the resection, per se. I know that there’s quite a bit of intrigue about checkpoint inhibitors with regard to adjuvant therapy, and you’ve been heavily involved in that arena. So what do you make out of this perioperative use of checkpoint inhibitors prior to surgery and with those results that I mentioned with the complete response?

Andrew X. Zhu, MD, PhD: Yeah. I think, Ghassan, this is a very intriguing and innovative approach, in my opinion. I think we’ve been gaining most of the experience of PD-1 [programmed cell death protein 1]–like molecules in the advanced stage. We know the drug is probably working in about 15% to 20% of the patient population. We have a very, very limited understanding of why this drug works in the selected population. We have actually tried to improve the outcome in the adjuvant setting with the targeted agents over the years and without any success. So I think with the emerging data of the checkpoint inhibitor in the advanced stage, I think 1 natural question is, can you move these drugs earlier? And also, more importantly, what is the drug actually doing to the tumor microenvironment, both to the tumor as well as the surrounding liver?

So you can imagine if you have a perioperative approach in a very well-conducted small study, you can actually address those questions. You actually have the luxury of looking at patients who are getting exposed to the drug and look at the surgical specimen. So I think mechanistically it’s a very, very interesting study. On the practical side, you can look at how this is actually going to be incorporated into the adjuvant or neoadjuvant setting, and there’s no doubt in my mind right now we’re not quite there yet. We have to see how the data is evolving in the adjuvant setting. I think to move directly to the neoadjuvant setting, I think we’re not quite there yet. But I think as an exploratory study, to look at the potential mechanism of action of this class of agents, I think this is a very innovative approach.

Transcript Edited for Clarity
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