When to Consider Systemic Therapy in HCC

Transcript:Richard Finn, MD: When we see a patient with liver cancer, we’re assessing both their underlying liver physiology and their tumor burden. When we’re talking about a patient with advanced liver cancer, someone who’s a candidate for systemic therapy, obviously they need to be able to come to clinic, they need to be functional, and they should have relatively preserved liver function—Child-Pugh A or Child-Pugh B that’s under control. Right now, we’ve had one agent that’s been shown to improve survival in advanced liver cancer, that’s sorafenib. That survival benefit has been maintained over almost a full decade now, and its survival benefit is proven in the Child-Pugh A group. The tumor characteristics of these patients are patients who have disease outside the liver, metastatic disease, patients who have multifocal tumor in the liver that is not amenable to chemoembolization or progressed after chemoembolization, or patients who have liver-confined disease and on imaging have evidence of tumor thrombus or tumor invasion into the portal vein or branches of the portal vein. All these patients would be considered for systemic treatment, either with sorafenib or even with a clinical trial. These are all characteristics of a patient with advanced disease who should receive systemic treatment.

Arndt Vogel, MD: When we think about systemic therapy, we first have to acknowledge that HCC is very chemotherapy-resistant tumors. And, for a long time, we did not have any systemic therapy available at all. Only with sorafenib, we had the first clinical trial in which we were able to achieve a survival benefit for patients with more advanced HCC, an increasing median overall survival of almost 3 months, which is quite okay, I think. And, with that, this is the standard of care for patients with advanced disease. When we think about the clinical trials that have been done, both in Caucasian and in Asian patients, these were also selected patients, and specifically in respect to the underlying liver disease.

So, in these trials, only patients with a good liver function were included based on the Child-Pugh criteria, and only Child-Pugh A patients were included. I think this is the main and most important point today. In Germany, for example, we could also use sorafenib in patients with more advanced disease, in Child-Pugh B stage, for example. But, the evidence we have is for patients with Child-Pugh A cirrhosis. This is important because if the patients have more advanced disease, liver function is bad and the survival itself of the patient due to this poor liver function might also be impaired. And we do not really know whether we increase survival when we treat our patients with sorafenib. When we think about systemic therapy, the most important point for our patients is that they are fit, that they are in a good performance status, and that the liver function is adequate, which means they should be in Child-Pugh A cirrhosis.

Richard Finn, MD: For a patient who has intermediate stage liver cancer—liver cancer that’s confined to the liver, they have a good performance status, their liver function is preserved—local regional therapies play a major role in controlling their disease. It’s not a cure, but patients can live longer. It has been shown to improve survival, at least with chemoembolization. With radioembolization, there are no randomized data that shows that it does improve survival, just single-arm phase II studies. But, since they’re not cured with chemoembolization, almost every patient, if they live long enough, will develop advanced disease. That is to say, they’ll develop disease outside the liver or they’ll have a recurrence shortly after chemoembolization. It’s important for us to recognize that transition point from what we would call Barcelona stage B to Barcelona stage C, and that’s that change from intermediate disease to advanced disease where we transition from local regional therapy to systemic therapy. And the cues for that are, as I mentioned, development of disease outside the liver or, even more commonly, development of multifocal disease within the liver, or vascular invasion in the liver. I think that because the disease is still in the liver, there’s a bias to still treat it with liver-directed therapy. But, we need to recognize that the data supporting that, as far as high level of evidence in those scenarios, do not necessarily exist for local regional therapies, and the data do exist for systemic therapy.

Transcript Edited for Clarity