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The Future of Immunotherapy in HCC

Panelists:Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center; Richard S. Finn, MD, Geffen School of Medicine; Riccardo Lencioni, MD, Sylvester Comprehensive Cancer Center; Amit Singal, MD, UT Southwestern Medical Center
Published: Wednesday, Jul 13, 2016


Transcript:

Ghassan K. Abou-Alfa, MD:
Richard, what’s going on?

Richard Finn, MD: There’s no doubt that immunotherapy has been a hot topic in oncology, initially with the CTLA-4 (cytotoxic T lymphocyte–associated antigen 4)–targeted agent, ipilimumab, and then nivolumab and pembrolizumab in melanoma, lung cancer, bladder cancer, and the list is ongoing. These drugs are designed to make tumors accessible to the immune system. And when we think about liver cancer, there’s been a lot of data that suggest that liver cancer might be a good target for immunotherapy, given that it arises in an inflammatory environment. There was an early study with tremelimumab, a CTLA-4 antibody, that showed some activity, but this was several years ago before immunotherapy really took on.

But what has got people’s attention were data presented at the ASCO meeting last year, which was a phase I and phase I expansion study of nivolumab in patients who had prior treatment, looking at its safety and efficacy in patients with hepatitis C, hepatitis B, or no underlying viral etiology. And the data were somewhat impressive. Again, they were small numbers, single-arm, uncontrolled, but they had an impressive 1-year survival. There were patients who were ahead of significant shrinkage, not just 30%, but significantly higher than that, near CRs. And, as we’ve seen in other solid tumors, these responses were long-lasting. So, now there’s a frontline study that’s being launched of nivolumab versus sorafenib in the frontline setting, and soon to follow will be pembrolizumab in the second-line setting.

Ghassan K. Abou-Alfa, MD: And, of course, also, we are looking at tremelimumab plus MEDI4736 (durvalumab)—which is an anti–PD-L1 inhibitor being looked at—in the second-line setting in a three-arm study. So, as you can see, there’s quite a lot going on. If anything, we urge you—and this is something I would like to hear Richard say again—that please, it’s not necessary that you apply immunotherapy out of a clinical trial in that setting because we heard about value, we heard about cost. At the same time, these are great studies where we need to really show that we achieve a benefit, and there’s no other way of doing it except by having patients on trials. Is there any role for immunotherapy that you would think about it going on with the local therapies, Riccardo?

Riccardo Lencioni, MD: Absolutely! I mean, this is, actually, theoretically the area that I really would like to see explored because, to me, the combination of some form of local or local regional therapy that will address the visible disease, plus an immune agent that will prevent or delay recurrences, can truly be a change of paradigm.

Ghassan K. Abou-Alfa, MD: That’s very important because, after all, it’s not necessarily the environment of what we learned from the melanoma world. What we learned from the lung cancer world is that the metastatic setting, with multiple prior therapies, may be where the immunomodulation or the checkpoint inhibitors might be applied. But, actually, the environment of the locally advanced disease and all the inflammation—and all the immune activity that may be occurring—by itself might be a great environment for unlocking that checkpoint and really inhibiting it to allow for this activity to happen. But, of course, clinical trials are needed, and we stress again that this is really where a lot of the resources should occur in regard to allocating patients with the appropriate trials.

We covered a lot. It’s fascinating how much is going on, and, if anything, we have reviewed a lot in terms of what’s available for the treatment in HCC, what’s emerging, and what options look most promising for managing the disease down the road. Before we end the discussion, I would love very much to at least ask for final thoughts, and I’ll start with Dr. Finn.

Richard Finn, MD: Well, I think it’s very easy to become discouraged by all the negative data that has occurred over the past several years, but we owe it to our patients to continue trying to move forward. For the general community oncologist, they maybe see a handful of patients with liver cancer a year. This isn’t lung cancer, breast cancer, colon cancer. And so I think that it really behooves them to have a patient seen in a large transplant-based multidisciplinary setting. Even if the patient ends up coming back to them for care, really, the optimal approach would probably be developed in that setting, and it’s certainly a way to get them access to clinical trials.

Ghassan K. Abou-Alfa, MD: Very nicely said. Riccardo?

Riccardo Lencioni, MD: Well, the point I will make is we heard about many options, really a broad spectrum for HCC, and sometimes we may have the feeling that there are competitors like surgery versus ablation, chemoembolization versus sorafenib. They are not competitors; they are complementary. And, actually, the best way to measure how a certain institution or medical center is doing well in HCC is to measure the level of consensus. In reality, when it comes to discussing individual patients, there is much more synergy and complementarity, rather than competition, among these different options. So, this is the key for the management of HCC: personalized decisions.

Ghassan K. Abou-Alfa, MD: Could not have been said better. And Dr. Singal. Amit?

Amit G. Singal, MD: I want to echo the thoughts that we just heard. I think the key thing is that HCC treatment is complex, with many treatment options. And so you really do get the best opinions and the best therapies when you’re referred in to a tertiary care center, where you have all of these subspecialties, you have multidisciplinary conferences, multidisciplinary clinics, as well as clinical trials. And then finally, from a hepatologist’s standpoint, I think the key thing to emphasize is that there’s a lot happening in terms of advanced disease and local regional therapy. But the best therapies are when you have cure, and then you can get a 5 year survival, 10-year survival. And we’re hoping we can get there with advanced therapies and locally regional therapies—but we’re not there yet. Really, the best way you can make yourself eligible for curative therapy is to be found early. So, your patients who have cirrhosis should be on a screening program, so we can find them early when they have curative therapies available.

Ghassan K. Abou-Alfa, MD: This is fascinating, what my colleagues just mentioned. If anything, despite all the great technology and despite all the scientific treatment that’s ongoing—which, definitely, we’re very thrilled about and we’re all part in witnessing, and I’m sure you do the same—it’s interesting. The collaborative effort that they’re bringing up is so critical to make sure we take care of patients with advanced HCC or even with localized HCC, to kind of forward the advancement of the cure. So, please, make sure you engage yourself in multidisciplinary meetings. There’s no reason at all to say you’re too busy not to go to the multidisciplinary meeting, no reason at all to not call your colleague, no reason at all to not check on clinical trials for your patients.

This has been a great discussion. Thank you very much, everybody. Thank you for joining us for this OncLive Peer Exchange.

Transcript Edited for Clarity
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Transcript:

Ghassan K. Abou-Alfa, MD:
Richard, what’s going on?

Richard Finn, MD: There’s no doubt that immunotherapy has been a hot topic in oncology, initially with the CTLA-4 (cytotoxic T lymphocyte–associated antigen 4)–targeted agent, ipilimumab, and then nivolumab and pembrolizumab in melanoma, lung cancer, bladder cancer, and the list is ongoing. These drugs are designed to make tumors accessible to the immune system. And when we think about liver cancer, there’s been a lot of data that suggest that liver cancer might be a good target for immunotherapy, given that it arises in an inflammatory environment. There was an early study with tremelimumab, a CTLA-4 antibody, that showed some activity, but this was several years ago before immunotherapy really took on.

But what has got people’s attention were data presented at the ASCO meeting last year, which was a phase I and phase I expansion study of nivolumab in patients who had prior treatment, looking at its safety and efficacy in patients with hepatitis C, hepatitis B, or no underlying viral etiology. And the data were somewhat impressive. Again, they were small numbers, single-arm, uncontrolled, but they had an impressive 1-year survival. There were patients who were ahead of significant shrinkage, not just 30%, but significantly higher than that, near CRs. And, as we’ve seen in other solid tumors, these responses were long-lasting. So, now there’s a frontline study that’s being launched of nivolumab versus sorafenib in the frontline setting, and soon to follow will be pembrolizumab in the second-line setting.

Ghassan K. Abou-Alfa, MD: And, of course, also, we are looking at tremelimumab plus MEDI4736 (durvalumab)—which is an anti–PD-L1 inhibitor being looked at—in the second-line setting in a three-arm study. So, as you can see, there’s quite a lot going on. If anything, we urge you—and this is something I would like to hear Richard say again—that please, it’s not necessary that you apply immunotherapy out of a clinical trial in that setting because we heard about value, we heard about cost. At the same time, these are great studies where we need to really show that we achieve a benefit, and there’s no other way of doing it except by having patients on trials. Is there any role for immunotherapy that you would think about it going on with the local therapies, Riccardo?

Riccardo Lencioni, MD: Absolutely! I mean, this is, actually, theoretically the area that I really would like to see explored because, to me, the combination of some form of local or local regional therapy that will address the visible disease, plus an immune agent that will prevent or delay recurrences, can truly be a change of paradigm.

Ghassan K. Abou-Alfa, MD: That’s very important because, after all, it’s not necessarily the environment of what we learned from the melanoma world. What we learned from the lung cancer world is that the metastatic setting, with multiple prior therapies, may be where the immunomodulation or the checkpoint inhibitors might be applied. But, actually, the environment of the locally advanced disease and all the inflammation—and all the immune activity that may be occurring—by itself might be a great environment for unlocking that checkpoint and really inhibiting it to allow for this activity to happen. But, of course, clinical trials are needed, and we stress again that this is really where a lot of the resources should occur in regard to allocating patients with the appropriate trials.

We covered a lot. It’s fascinating how much is going on, and, if anything, we have reviewed a lot in terms of what’s available for the treatment in HCC, what’s emerging, and what options look most promising for managing the disease down the road. Before we end the discussion, I would love very much to at least ask for final thoughts, and I’ll start with Dr. Finn.

Richard Finn, MD: Well, I think it’s very easy to become discouraged by all the negative data that has occurred over the past several years, but we owe it to our patients to continue trying to move forward. For the general community oncologist, they maybe see a handful of patients with liver cancer a year. This isn’t lung cancer, breast cancer, colon cancer. And so I think that it really behooves them to have a patient seen in a large transplant-based multidisciplinary setting. Even if the patient ends up coming back to them for care, really, the optimal approach would probably be developed in that setting, and it’s certainly a way to get them access to clinical trials.

Ghassan K. Abou-Alfa, MD: Very nicely said. Riccardo?

Riccardo Lencioni, MD: Well, the point I will make is we heard about many options, really a broad spectrum for HCC, and sometimes we may have the feeling that there are competitors like surgery versus ablation, chemoembolization versus sorafenib. They are not competitors; they are complementary. And, actually, the best way to measure how a certain institution or medical center is doing well in HCC is to measure the level of consensus. In reality, when it comes to discussing individual patients, there is much more synergy and complementarity, rather than competition, among these different options. So, this is the key for the management of HCC: personalized decisions.

Ghassan K. Abou-Alfa, MD: Could not have been said better. And Dr. Singal. Amit?

Amit G. Singal, MD: I want to echo the thoughts that we just heard. I think the key thing is that HCC treatment is complex, with many treatment options. And so you really do get the best opinions and the best therapies when you’re referred in to a tertiary care center, where you have all of these subspecialties, you have multidisciplinary conferences, multidisciplinary clinics, as well as clinical trials. And then finally, from a hepatologist’s standpoint, I think the key thing to emphasize is that there’s a lot happening in terms of advanced disease and local regional therapy. But the best therapies are when you have cure, and then you can get a 5 year survival, 10-year survival. And we’re hoping we can get there with advanced therapies and locally regional therapies—but we’re not there yet. Really, the best way you can make yourself eligible for curative therapy is to be found early. So, your patients who have cirrhosis should be on a screening program, so we can find them early when they have curative therapies available.

Ghassan K. Abou-Alfa, MD: This is fascinating, what my colleagues just mentioned. If anything, despite all the great technology and despite all the scientific treatment that’s ongoing—which, definitely, we’re very thrilled about and we’re all part in witnessing, and I’m sure you do the same—it’s interesting. The collaborative effort that they’re bringing up is so critical to make sure we take care of patients with advanced HCC or even with localized HCC, to kind of forward the advancement of the cure. So, please, make sure you engage yourself in multidisciplinary meetings. There’s no reason at all to say you’re too busy not to go to the multidisciplinary meeting, no reason at all to not call your colleague, no reason at all to not check on clinical trials for your patients.

This has been a great discussion. Thank you very much, everybody. Thank you for joining us for this OncLive Peer Exchange.

Transcript Edited for Clarity
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