Novel Approaches to Treatment of Hepatocellular Carcinoma - Episode 3

Frontline Therapy for HCC: Optimizing Treatment Selection


Richard Finn, MD: We’ve seen data and we’re going to talk about sequencing these drugs. But both these studies—when I say both, I mean the development of sorafenib, the development of lenvatinib—were done in patients who had preserved liver function. There’s clinical research, which proves a concept that the drugs are active, that they change outcome, and then there’s clinical practice. And I think one of the things that us in the academic arena are concerned about is we’re getting all these new drugs, but are patients in the condition to maximize the benefit from them? And what do you do for patients who have diminished liver function? Are you offering them either drug? Does it weigh into your decision? Is it any treatment versus no treatment?

Anthony El-Khoueiry, MD: It’s a very difficult question, and a lot of clinical judgment is involved. When we say diminished liver function, there’s a whole range. There’s the patient, as I noted earlier, who has really decompensated cirrhosis with ascites requiring paracentesis, active encephalopathy, more in the BCLC-D [Barcelona Clinic Liver Cancer-stage D] category. And these patients should not have their cancer treated. At this point, we don’t know that any cancer therapy would be tolerable and that any cancer therapy is going to extend their survival in a meaningful fashion. Because their mortality is more likely to be driven by their underlying liver disease.

Patients in the intermediate liver dysfunction range, meaning patients who have slightly elevated bilirubin, low albumin, are manageable on diuretics, and do not require active paracentesis, are probably patients who may benefit from some cancer therapy. And this is where the extrapolation happens. Now, when we talk about sorafenib and lenvatinib in let’s say Child-Pugh B, I don’t think one can choose one or the other based on any scientific data. We have more experience with sorafenib so far with registries and some data in Child-Pugh B patients, not randomized data, but at least some safety data. With lenvatinib, hopefully that will emerge over time. But really it comes back to clinical judgment for these patients.

Richard Finn, MD: So, we have 2 drugs in frontline. We talked about the importance of getting patients in good shape before they’ve gone through extensive locoregional treatment. Yttrium-90 [Y-90], in closing on this frontline discussion, that’s another locoregional approach. It’s been looked at pretty extensively in intermediate disease, in the context of patients who are TACE [transarterial chemoembolization] appropriate. But, in the context of systemic treatment, there’s been a move by some to say, “Well, you progressed on TACE, and instead of going to first-line lenvatinib or sorafenib, I’m going to do another Y-90.” What can you sum up about the recent data with Y-90 versus systemic treatment?

Anthony El-Khoueiry, MD: I think we can go to the recently reported trials, the SARAH and the SIRveNIB studies, which both compared Y-90 versus sorafenib for patients with advanced disease in the liver, no extrahepatic metastases. And both of these studies were negative, both in the intent-to-treat, as well as the treated per protocol population. So, the studies were designed to show the superiority of Y-90 over sorafenib, and they were negative in that sense. Whereas, the danger a bit is in the interpretation that these studies may show that Y-90 is noninferior to sorafenib. But that was not the intention or the design of these trials. And I think that would be a misinterpretation of the data at this point.

Richard Finn, MD: So, in frontline, it’s exciting. We have options. Obviously, regarding how we decide which drug to use, I think we’re still evolving those paradigms, and we’ll look forward to further analyses to help guide us a little more rather than expert opinion but some data-driven approaches.

Anthony El-Khoueiry, MD: Absolutely.

Transcript Edited for Clarity