Hepatocellular Carcinoma: Practical Implications of Emerging Data - Episode 18

HCC: Emerging Therapies Under Investigation

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Richard S. Finn, MD: We have a lot of tools in our toolbox now, and we spent a lot of time talking about how best to use these. Obviously, there are still a fair number of data gaps, but let’s look to the future. We heard at ASCO about a new TKI actually 2 of them, but donafenib was a TKI that beat sorafenib. Apatinib is another VEGF multikinase inhibitor that had data from China showing that it improves survival versus placebo in the second-line after a population that had mostly chemotherapy in the frontline. Moving away from the TKIs and checkpoint inhibitors, we’re seeing an interest in cellular-based therapies now, certainly in liver cancer. There are modified T-cell approaches geared toward AFP, traditional CAR T-type approaches versus AFP and even glypican 3 [GPC3], another protein that’s expressed in liver cancer. Katie, what are your thoughts about the next 5 years? What’s the next big breakthrough? I won’t hold you to it.

R. Kate Kelley, MD: It’s really hard to project. Although I’m also excited to see the direction of these cellular therapies, they are a level of intensity in terms of the preparative regimen and the tissue requirements for profiling, and it’s particularly difficult for HCC given the comorbid liver disease and comorbid viral disease in some cases. It’s a higher bar than many other tumor types. So I’m eagerly awaiting the efficacy results. We’ll be paying attention to the toxicity in those studies and with close detail.

One of the game-changing results would be a biomarker of I/O monotherapy response because PD-1 or PD-L1 inhibition, there is a reproducible percentage of 15% of patients who have extraordinary responses to monotherapy. That would be the game changer that helps us in our sequencing and helps us interpret our combination data, because when you have this powerful undisclosed biomarker among your results, it makes it very difficult to compare studies and results apples to oranges. That’s the game changer I’d like to see us focus on, difficult though it may be.

Richard S. Finn, MD: There have been a lot of interesting data, right? There’s a whole story around beta-catenin mutations and their association with response to I/O. There are signatures that have been associated with various T-cell infiltrates or an immune “hot” liver cancer versus an immune “cold.” Those are all very exciting, but I am challenged because the melanoma group hasn’t come up with that. The lung cancer group doesn’t have a great story. Will liver cancer be able to leapfrog those areas that have been at it so much longer? Hopefully, yes.

The other thing is that in the next 5 years, hopefully we’ll see some of these systemic drugs moved into earlier-stage settings. There are a whole host of studies looking at chemoembolization in combination with doublets of I/O and singlets of I/O, as well as the traditional postresection adjuvant-type studies, using these after curative approaches. It’s a very exciting time. Still, we need to refer patients to clinical trials in all stages because, at the end of the day, clinical trial enrollment is always a challenge. The majority of patients in any disease are typically not clinical trial candidates. When we do see someone who’s fit—Child-Pugh A, minimal portal hypertension—it really behooves us to try to get them into a research program. Hopefully now, in the future, we’ll see the COVID-19 crisis settle down, and that will help us revamp our research priorities in patient care.

Transcript Edited for Clarity