Hepatocellular Carcinoma: Practical Implications of Emerging Data - Episode 4

Locoregional and Systemic Therapy for HCC

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Richard S. Finn, MD: Reena, we want to find liver cancer early because presumably it’s the most curable—resection, transplant, even radiofrequency ablation in small tumors. How do we think about the clinical aspect of liver cancer, specifically staging? Can you speak to Barcelona [Clinic Liver Cancer staging system]? Because I think that’s probably what people hear the most now. It’s used the most, the BCLC.

Reena Salgia, MD: Yeah, that’s correct. Most commonly, we’ll use the Barcelona Clinic Liver Cancer staging system, or BCLC. And through the multidisciplinary liver tumor boards that I think most of us participate in on this panel, that’s really where we tend to link the staging with treatment options for patients. The advantage of BCLC being that it’s combining not just the tumor burden, but also the specific liver function as judged by the Child-Pugh status of the patient, knowing that most of these patients have a background of chronic liver disease or cirrhosis, and then also integrating the performance status, so all 3 parts, and then being able to further subdivide them into the options for treatment and prognosis.

Richard S. Finn, MD: Probably the most common group of patients we see at presentation are patients with intermediate liver cancer. If anyone thinks otherwise, please let me know. Certainly, we see all stages. And hopefully, as we have earlier diagnosis, we’re seeing more patients with stage 0 or stage A, which is curable. But a lot of them are stage B, which are intermediate. These are patients who generally have well-compensated liver disease and multifocal tumor in the liver but do not have extrahepatic disease and do not have invasion to the vasculature. Historically, the standard of care for these patients has been locoregional treatment, such as chemoembolization and increasingly radioembolization with Y-90 [yttrium-90]. Some of these patients will be considered for transplant, they can be down-staged to transplant. I think this is a whole other discussion beyond the scope today, but I think highlights the point that these patients should be seen at a multidisciplinary program for an evaluation because of the importance of surgery and interventional radiology expertise. As compared to those patients who we’re talking about who are advanced, a lot of those patients would get systemic treatment, who have symptomatic disease, they have extrahepatic spread, or they have vascular invasion into the blood vessels of the liver. Certainly, a patient can stage-migrate. Someone with intermediate disease can progress beyond TACE [transarterial chemoembolization], or locoregional treatment, and become truly advanced, or even a patient who has [BCLC] stage B intermediate disease without vascular invasion or extrahepatic spread might be a patient for systemic treatment.

So Katie, all of us here see a lot of these patients, and we rattle these terms off pretty easily. But I think in clinical practice, as we have evolved into so many more treatment options, it’s going to be very important for the people in the trenches in the front line in the liver cancer space in oncology clinics, and hepatology clinics and GI [gastrointestinal] clinics, to have an understanding of this. Could you build out the multidisciplinary platform and stage migration and treatment decisions?

R. Kate Kelley, MD: I think this is a great area of discussion, and it’s important to reiterate the historical context here to remember that really, from 2007 until 2017, we had but 1 treatment available for systemic therapy, which was sorafenib. After that, there were clinical trials certainly, but very limited options for the majority of patients. That led to the evolution of locoregional therapy as the predominant mainstay of therapy for intermediate and sometimes even early advanced stages of HCC [hepatocellular carcinoma], and it’s really incumbent upon us now to reexamine the data, both for liver drug therapies, but also place it into context of the new systemic therapies. I think it’s important for us to remember that we do have limited prospective data for liver-directed therapies, particularly in the more advanced BCLC stage B space where the patients are having more than 3 to 5 lesions or getting more than 1 or 2 TACE procedures. Beyond those thresholds, we don’t have randomized trial data to confirm outcome benefit in large prospective trials. Likewise, we know from radioembolization trials that patients with more advanced stages of disease really do better with sorafenib, where there is no survival benefit to radioembolization in randomized trials compared to sorafenib in more advanced patients.

I think now that we have level 1 survival benefit in patients with unresectable, incurable HCC, including BCLC B or intermediate-stage patients, we need to be very careful about the use of locoregional therapies in patients who might have a survival benefit preferentially from systemic therapy. There are tools at our disposal to use, not all of them as well-validated as we may like, but for example, the prospective hepatic arterial embolization prognosis score that can help stratify patients according to their likelihood of benefit from TACE procedures, or patients who have already had a TACE procedure to look at toxicity and response such as the ART [Assessment for Retreatment with TACE] score. Those can help us potentially triage patients to switch over to systemic therapy, depending on their performance and their scoring. Now, all of this is complicated and absolutely enhances the importance of the multidisciplinary tumor board contexts, because these are complex decisions and lots of variables, including not only tumor response, but also liver function or deterioration thereof. I think that with this increase in options for systemic therapies, it requires us in medical oncology to become more present in the multidisciplinary tumor board setting to help guide and educate on the multiple therapies that we now have available.

Richard S. Finn, MD: You bring up some very important points. One of the concerns I think in continuing locoregional treatment beyond progression is that it could affect liver function. Amit, I know you’ve done some of these analyses. Continued locoregional treatment, while it’s very focused, very targeted, can you comment on its effect on the liver function over time?

Amit Singal, MD: Yes, what we see is that as Katie mentioned these scores, you can see that some people, when you go through locoregional therapy, you start to see basically off-target effects. You see some degree of injury to the background liver, and when you do this over and over again, just like any chronic injury, you can have deterioration of liver function. The most important reason that we have to consider this is because essentially, if somebody has worse liver function, then we may not be able to actually use these systemic therapies. I think that’s why we’re all becoming much more cognizant in terms of this appropriate time to transition and trying to maximize not only the benefit of locoregional therapy, but also maximizing the benefit and the availability of these systemic therapies.

Transcript Edited for Clarity