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Emerging Agents for Treatment of HCC

Panelists: Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center; Richard S. Finn, MD, Geffen School of Medicine at UCLA; Masatoshi Kudo, MD, PhD, Kindai University Faculty of Medicine; Arndt Vogel, MD, Hannover Medical School
Published: Tuesday, Oct 02, 2018



Transcript: 

Ghassan K. Abou-Alfa, MD: Rich, you mentioned something else about, like, a drug that has been tested and was evaluated. And until recently, there was a small piece of data coming in regard to bevacizumab plus atezolizumab. So, tell us that combination of a TKI plus a checkpoint inhibitor.

Richard S. Finn, MD: There’s this evolving story that altering the microenvironment changes the sensitivity to checkpoint inhibition. And I think many of us—and certainly I’m guilty of this—we’ve traditionally thought about a drug like bevacizumab or ramucirumab as just working on the endothelial cells. But as science has evolved, it looks like there’s more effect than that. Certainly, they just work on the endothelial cells, because that’s where the VEGF receptor or VEGF ligand works. But there are other effects downstream from blocking the VEGF receptor, and those are things that can affect antigen-presenting cells, immune effector cells.

And there are now data both with bevacizumab and atezolizumab, a PD-L1 antibody, as well as lenvatinib, a VEGF/FGF inhibitor, with pembrolizumab in diseases outside of liver cancer that show that these combinations are giving response rates much higher than anticipated with either drug alone. And now those data are spilling over into liver cancer, and there are data being presented at this meeting, actually, with both of those combinations. There are data being presented with the combination of atezolizumab and bevacizumab from a phase I and phase I expansion, as well as the similar data with pembrolizumab and lenvatinib. The IMbrave150 study has been launched. That’s a large global randomized phase III study of bevacizumab and atezolizumab versus sorafenib. That’s a very exciting idea of combining now 2 biologics.

Ghassan K. Abou-Alfa, MD: That’s incredible. If anything, we left all the drugs barely within the year that we’re able to add, and on top of it now we have all the new thoughts. It’s good that we are really so dynamically active and looking into new options as we speak. This is really incredible. We had a great time listening to all of you. It would be nice maybe to hear, like, final thoughts—maybe 1 word or 2 from Dr. Kudo. Your thoughts—anything, finally, you would like to tell us.

Masatoshi Kudo, MD, PhD: Compared with the past 10 years, now we and the patients are very happy to have a choice—the option—of 2 first-line and second-line drugs and sooner or later, 4, 5.

Ghassan K. Abou-Alfa, MD: Three, yes; maybe 4.

Masatoshi Kudo, MD, PhD: Now 3, 4. The I-O will be coming, and also, I’m very much expecting combinations—I-O plus I-O, I-O plus TKI, or I-O plus locoregional therapy—in the adjuvant setting.

Ghassan K. Abou-Alfa, MD: I’m glad to hear about your optimism. This is great. Arndt, any final thoughts?

Arndt Vogel, MD: Yes. So, I think I can just agree that times are really changing and have changed in the past 2 years. And we have now really a lot of drugs available. We have negative data for local therapies. So, it’s very clear that systemic therapy will have a much bigger impact on the treatment of HCC in the future. And I think it’s just at this point in time, and you already mentioned that we have all these interesting combinations coming. I think at the moment, the field is really moving so fast. It’s so exciting—in the data Rich had mentioned with the combination with lenvatinib and Avastin (bevacizumab) and combination with immunotherapy, really high response rates that we have not seen before for systemic therapy. So, I think these are really exciting times, and I think we are really moving forward very fast and will improve survival of our patients really in the future with these combinations.

Ghassan K. Abou-Alfa, MD: I’m glad to hear that optimism, as well, which is great. And Rich, final thoughts for you?

Richard S. Finn, MD: You said 2 words. So, I would say patient selection is very important in every intervention we do. It has to start with the early-stage patients. Because, again, we can have this great discussion about the exciting new systemic agents, but if the patients who are being treated by these new drugs are very sick and decompensated, they’re not going to do well. I don’t think that’s what we’re trying to do. We’re trying to select patients and triage them to the right treatments based on evidence.

Ghassan K. Abou-Alfa, MD: Great thoughts. Well, if anything, thank you all for your contributions to this discussion. And on behalf of our panel, we thank you for joining us, and we hope you found the OncLive® Peer Exchange® to be useful and informative.

Transcript Edited for Clarity 

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Transcript: 

Ghassan K. Abou-Alfa, MD: Rich, you mentioned something else about, like, a drug that has been tested and was evaluated. And until recently, there was a small piece of data coming in regard to bevacizumab plus atezolizumab. So, tell us that combination of a TKI plus a checkpoint inhibitor.

Richard S. Finn, MD: There’s this evolving story that altering the microenvironment changes the sensitivity to checkpoint inhibition. And I think many of us—and certainly I’m guilty of this—we’ve traditionally thought about a drug like bevacizumab or ramucirumab as just working on the endothelial cells. But as science has evolved, it looks like there’s more effect than that. Certainly, they just work on the endothelial cells, because that’s where the VEGF receptor or VEGF ligand works. But there are other effects downstream from blocking the VEGF receptor, and those are things that can affect antigen-presenting cells, immune effector cells.

And there are now data both with bevacizumab and atezolizumab, a PD-L1 antibody, as well as lenvatinib, a VEGF/FGF inhibitor, with pembrolizumab in diseases outside of liver cancer that show that these combinations are giving response rates much higher than anticipated with either drug alone. And now those data are spilling over into liver cancer, and there are data being presented at this meeting, actually, with both of those combinations. There are data being presented with the combination of atezolizumab and bevacizumab from a phase I and phase I expansion, as well as the similar data with pembrolizumab and lenvatinib. The IMbrave150 study has been launched. That’s a large global randomized phase III study of bevacizumab and atezolizumab versus sorafenib. That’s a very exciting idea of combining now 2 biologics.

Ghassan K. Abou-Alfa, MD: That’s incredible. If anything, we left all the drugs barely within the year that we’re able to add, and on top of it now we have all the new thoughts. It’s good that we are really so dynamically active and looking into new options as we speak. This is really incredible. We had a great time listening to all of you. It would be nice maybe to hear, like, final thoughts—maybe 1 word or 2 from Dr. Kudo. Your thoughts—anything, finally, you would like to tell us.

Masatoshi Kudo, MD, PhD: Compared with the past 10 years, now we and the patients are very happy to have a choice—the option—of 2 first-line and second-line drugs and sooner or later, 4, 5.

Ghassan K. Abou-Alfa, MD: Three, yes; maybe 4.

Masatoshi Kudo, MD, PhD: Now 3, 4. The I-O will be coming, and also, I’m very much expecting combinations—I-O plus I-O, I-O plus TKI, or I-O plus locoregional therapy—in the adjuvant setting.

Ghassan K. Abou-Alfa, MD: I’m glad to hear about your optimism. This is great. Arndt, any final thoughts?

Arndt Vogel, MD: Yes. So, I think I can just agree that times are really changing and have changed in the past 2 years. And we have now really a lot of drugs available. We have negative data for local therapies. So, it’s very clear that systemic therapy will have a much bigger impact on the treatment of HCC in the future. And I think it’s just at this point in time, and you already mentioned that we have all these interesting combinations coming. I think at the moment, the field is really moving so fast. It’s so exciting—in the data Rich had mentioned with the combination with lenvatinib and Avastin (bevacizumab) and combination with immunotherapy, really high response rates that we have not seen before for systemic therapy. So, I think these are really exciting times, and I think we are really moving forward very fast and will improve survival of our patients really in the future with these combinations.

Ghassan K. Abou-Alfa, MD: I’m glad to hear that optimism, as well, which is great. And Rich, final thoughts for you?

Richard S. Finn, MD: You said 2 words. So, I would say patient selection is very important in every intervention we do. It has to start with the early-stage patients. Because, again, we can have this great discussion about the exciting new systemic agents, but if the patients who are being treated by these new drugs are very sick and decompensated, they’re not going to do well. I don’t think that’s what we’re trying to do. We’re trying to select patients and triage them to the right treatments based on evidence.

Ghassan K. Abou-Alfa, MD: Great thoughts. Well, if anything, thank you all for your contributions to this discussion. And on behalf of our panel, we thank you for joining us, and we hope you found the OncLive® Peer Exchange® to be useful and informative.

Transcript Edited for Clarity 
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