Future of Frontline Combination Therapy in Advanced HCC

Transcript: Andrew Zhu, MD, PhD: If any of these combination treatments will improve the overall survival, Nik, how would you envision moving forward? How will you treat advanced hepatocellular carcinoma?

Nikolaos Pyrsopoulos, MD, PhD: Andrew, I’m a transplant hepatologist. Ultimately, if we reach the point where we can get the disease under control, especially for patients with unresectable nonmetastatic hepatocellular carcinoma, this will be the optimal idea for me. I’m sure you are targeting the same things, because there are different downstaging protocols or bridging therapy to transplant. Also, we’re trying to get to the point at which the overall survival is increased, even for patients, but they’re not deemed to be transplant candidates. This is a wonderful opportunity for the patients and their families. Of course, tied up with the adverse-event profile, that is not so serious, and patients can tolerate the treatment so they will have a good quality of life. This will be optimal.

Apparently, we are at the stage where there are compounds, there are monotherapies, but what we have been taught in the past was that combination and especially combination of compounds that act synergistically without competing against one another for the same target, will be the way to go. I will not be surprised if I will see 2 and 3 compounds as first-line therapy in the future.

Andrew Zhu, MD, PhD: Very interesting that you mention that.

Nikolaos Pyrsopoulos, MD, PhD: Because definitely we have 2 different categories of immuno-oncology agents, and we have tyrosine kinase inhibitors [TKIs] that might have a different action. Even within the same category of TKIs, there is a different panel of tyrosine kinases inhibitor. You see that 1 is inhibiting the FGF [fibroblast growth factor]; the other 1 is c-MET, as we will be discussing later.

Andrew Zhu, MD, PhD: Very nice, Nik. I definitely like your enthusiasm. I think as we will see, with the improvement of the combination treatment, we’re already talking about downstaging potentially. Some of these patients may even potentially convert from the unresectable setting to resectable setting. Also this concept of applying this active systemic regimen in the adjuvant setting is being investigated. This is a very great investigation in an area of unmet medical need, in my opinion. I also like your enthusiasm of even considering even more active agents, bringing a 3-drug combination in down the road. Obviously, we have to see if whether these drugs can be combinable, whether the safety profile is acceptable.

Transcript Edited for Clarity