DR LLOVET: What is the rationale to treat this patient at advanced stage with sorafenib? Here you have the New England paper where we were comparing sorafenib versus placebo, around 600 patients randomized 1 to 1. And the median survival for sorafenib was roughly 11 months. It was 10.8 months. And for placebo it was 7.8 months. So we identified a 3-month survival difference for these patients if they received sorafenib.

And in the left-hand side, you have here the actual recommendation. Sorafenib is the standard systemic therapy for HCC. And it is indicated in patients with preserved liver function, Child-Pugh A class. That is the case of this patient. And with advanced tumors, BCLC C, this patient has this stage because you have portal vein invasion and you have ECOG performance status 1, or tumors progressing to local-regional therapies, such as the case of the patient that is progressing to chemoembolization. So this provides the rationale to treat the patient with sorafenib.

So the question then was, okay, you have this patient with advanced stage, portal branch invasion, and the question is, what survival can you expect in this patient? And in this subgroup analysis paper, it was pretty clear that patients with what we call macrovascular invasion on sorafenib, the median survival is around 8 months, as opposed to 4.9 or 5 months for patients with treatment allocated to the placebo arm. So this is the subgroup analysis of, effectively, the patient we are talking about. We are talking about the patient with macrovascular invasion. So we are expecting, with sorafenib, 8-month median survival as opposed to 5-month for placebo. Also, in terms of ECOG performance status, we’re expecting around 9 months for sorafenib and around 5.6 months for placebo.

So one alternative that has been proposed, particularly by some surgeons, is that you can treat macrovascular invasion in HCC with surgical resection. I’m showing here some of the studies. All these studies are small studies, retrospective analyses, underpowered, with selection bias — they are only reporting the ones that survive. And there is no intention-to-treat analysis. So it’s hypothesis generating.

I’m showing the best study on the left-hand side with a median survival of 13 months, but of course this cannot be accepted as a standard of care and we need randomized studies.

DR LOVE: So essentially — is this looking essentially at palliative surgical resection?

DR LLOVET: That’s right, yes. You are removing the tumor and you are removing the macrovascular invasion. And despite of that, you have 13-month median survival. But if this was the case for all the patients, it’s something that you may consider. However, when reporting this type of patients, of course you are not reporting the ones that are not candidates, so there is lack of intention to treat. And the studies, if you check the number of patients included in some of the studies, these are really underpowered, these studies. Next slide.

Another alternative is to keep maintaining chemoembolization. There are a few studies, and the outcome is not very good, as you can see: 5, 3, 6-month median survival. So there are some physicians, particularly in Asia, that consider that you can keep doing chemoembolization when you have portal invasion. But this is hypothesis generating, but there is no strong data. Next slide.

And then the most appealing treatment beyond systemic therapy with sorafenib is internal radiation with yttrium-90. There are some prospective studies that I’m showing in this slide, in the upper side, where you can achieve, in a small series, around 10 to 11-month median survival for patients with vascular invasion, branch portal vein invasion. So this is hypothesis generating, may compete with sorafenib. What we have to do? Randomized studies.

In the bottom of this slide I’m showing the table of the 4 randomized controlled trials that we have ongoing at this point, comparing sorafenib with yttrium-90. And we will have the results by late this year in almost all of them. So we will know whether yttrium-90 as a stand-alone treatment is better, or not, than sorafenib, or yttrium-90 plus sorafenib is better than sorafenib. And we will have an answer to this question. So as per now the standard of care is only sorafenib.

DR LOVE: Could you talk about what actually happened to this patient?

DR LLOVET: Yes. This patient, at the end, progressed. And now he’s still in progression with sorafenib, but still alive.

DR LOVE: So he’s on sorafenib now and he’s —

DR LLOVET: No. He was on sorafenib for a period of time, and then we switched the patient because upon progression you have different alternatives that I can explain to you. At that time point, we include the patient in a trial.

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