Multimodality Management of Advanced Liver Cancer - Episode 9

Hepatocellular Carcinoma: Future Directions in Care


Ghassan K. Abou-Alfa, MD, MBA: Riccardo, back to you, you’ve been amazing in regard to all of your career, the connectivity with the oncologist and trying to build the relationships. TACE [transarterial chemoembolization] plus, as you said, you were the first to do the SPACE study, sorafenib didn’t work. And you remember in the beginning we spoke about how we’re going to hold that thought in regard to what to combine the TACE with. Tell us about the checkpoint inhibitors, your thoughts.

Riccardo Lencioni, MD, FSIR, EBIR: Well, as I say, there are several studies that essentially are exploring the different combinations using different locoregional therapies, particularly TACE but also Y-90 [yttrium-90] radioembolization. And then with either concurrent or sequential use of checkpoint inhibitors, plus/minus additional drugs, such as the VEGF inhibitors. In particular there is one phase III study that has already been started, it’s the first phase III investigating in particular patients with intermediate-stage HCC [hepatocellular carcinoma], so those who are candidates for TACE. TACE is the standard of care for this patient population. The study will have TACE and placebo, TACE plus durvalumab, and TACE plus durvalumab followed by bevacizumab. So we will have an understanding I think in terms of how we can truly jump to a brand new level in terms of survival. Because this, unfortunately, has not been the case. As I said before, despite all this technological improvement and the ability to do better TACE, the bottom line in terms of survival has remained relatively unchanged over the years. Yes, there has been an improvement, but we aim for more.

Ghassan K. Abou-Alfa, MD, MBA: Fair enough. What Riccardo just said is critical because we did realize and we did prove that TACE plus a TKI [tyrosine kinase inhibitor] did not work. On the other hand, TACE plus a checkpoint inhibitor is being worked up, I like very much the idea that Riccardo brought up about TACE plus a checkpoint inhibitor also with an antiangiogenic, which is the durvalumab plus bevacizumab plus TACE. The EMERALD-2 study actually is going to be very intriguing.

This brings us to the point, which is quite critical, are all the TKIs being understood as also being anti-VEGF, or is there a certain particularity about the bevacizumab and durvalumab plus TACE such that we get a little bit more advantage? Time will tell, we’ll just have to wait and see. With this said, I would like to go back to another point by everybody, and I will ask Mike. Please, just 1 sentence so we can wrap it up. And I will pick up the subject with you of your choice of TKIs in second line. One sentence.

Michael A. Morse, MD, MHS, FACP: One sentence. It’s good to have choice, and that’s what I present to patients, there are choices.

Ghassan K. Abou-Alfa, MD, MBA: Fair enough, I totally agree, and it’s good that you have that many choices. I would say that the conditional 2 things of regorafenib with prior sorafenib and ramucirumab with the AFP [alpha-fetoprotein] interestingly give a little bit of an open highway for cabozantinib anyway. For you, Catherine, the question is, in regard to the checkpoint inhibitors, what do we need to understand about the immunity of the liver to begin with? PD-1 [programmed cell death protein 1], PD-L1 [programmed death-ligand 1], or a combination with CTLA-4 [cytotoxic t-lymphocyte—associated protein 4]?

Catherine Frenette, MD, FAST, AGAF: I think that we’re going to end up with a combination as the best response, but we also need to protect the liver during all of this. And I think the most important thing is, again, taking it back to the multidisciplinary tumor board and making sure that the patient’s liver function stays good enough to have access to all the different lines of therapy that we have.

Ghassan K. Abou-Alfa, MD, MBA: Absolutely. That’s what is quite intriguing, and we just have to wait until we see more of the data of the nivolumab versus sorafenib, as well as wait for the critical data that we will get on the durvalumab plus tremelimumab. Tim, adjuvant therapy. I didn’t ask about that yet. One sentence about the prospect in regard to an adjuvant checkpoint inhibitor.

Tim F. Greten, MD: Well, as I said, I think it’s a very interesting approach and obviously we will get to answer all the other questions you asked way earlier, and it will take just some time to figure this out. But I’m looking very much forward to those data.

Ghassan K. Abou-Alfa, MD, MBA: Absolutely. And lastly Riccardo, tell us one more time, I’d love to hear it from you, TACE plus the durvalumab plus bevacizumab. Your thoughts?

Riccardo Lencioni, MD, FSIR, EBIR: Well, if I can say something more general, at this point I think for hepatocellular carcinoma, clearly having multiple options is extremely important. And we have seen progress with this. Let’s say in the past for early tumors, everybody was going to resection, and resection didn’t really have outstanding outcomes. With the advent of interventional therapies, then patients are better selected, and this is I think a major improvement. Now I see something similar, for instance, in the intermediate stage where because of the availability of effective systemic drugs, we can better select patients who will go toward the TACE.

Ghassan K. Abou-Alfa, MD, MBA: Absolutely. I totally agree with you on that, this is quite intriguing. I agree with you, we just have to wait for the durvalumab plus TACE data. With this said, amazing. Thank you for being here. Thank you all for your contributions to the discussion. On behalf of our panel we thank you for joining us, and we hope you found this Peer Exchange discussion to be useful and informative, and we wish you a great day. Thank you very much.

Transcript Edited for Clarity