Ghassan K. Abou-Alfa, MD: Let’s carry on a little bit further on TACE. You brought up very important points and among which were those that were done in a very exclusive fashion. If I’m not mistaken, I think the median size in the 2 TACE studies that were positive was, like, about 3 cm or 4 cm, no more than that.
Richard S. Finn, MD: No more than 5 cm, but still.
Ghassan K. Abou-Alfa, MD: Fair enough. But nowadays with TACE, is there a limit for how big of a tumor it is to TACE it?
Richard S. Finn, MD: Well, this goes back to our discussion about staging. You can say that a tumor is intermediate stage, but are the data necessarily linking an intervention with improving an outcome? So, the TACE studies that were originally done were in the late ’90s, early 2000s showed that TACE versus placebo—so no treatment in this group of patients—improved survival. And, again, there was no drug approved until 2007 for advanced liver cancer or unresectable, we should even say, and unresectable includes both B and C. But TACE has filled a void for those patients. And the question isn’t, can I do a TACE? The question is, will doing a TACE be effective? And that’s a very important question that you need to ask your interventionalist and at your tumor boards.
Ghassan K. Abou-Alfa, MD: What’s the perception of patients in Germany in regard to TACE? Is this something sought after, that they look for?
Arndt Vogel, MD: So, I think TACE is clearly also in Germany the most frequently used first-line treatment in HCC. But I think it’s really important, since we have no more systemic treatments available, that we really look at the evidence we have for TACE. And we always say that we have level 1 evidence for TACE, but I think that we shouldn’t forget that there are a couple of trials; many of them are negative, and we basically just have 2 positive trials.
Ghassan K. Abou-Alfa, MD: Fourteen negative.
Arndt Vogel, MD: Right, even more. So, we have 2 positive trials, and the 1 positive trial—and you mentioned it—it was a highly selected patient group. They treat 950 patients, and in the final analysis, there were less than 100 patients, 45 and 50. And then I think it’s also important to look at the numbers. Overall survival in this selected group of patients was 28 months. I think that with cross-trial comparison, although that’s difficult, we need to remember these numbers. Even in this highly selected patient population, we have 28 months, which is obviously the best we can get. In this trial, in the control group without any effective treatment, median overall survival was 18 months, which kind of indicates that we have a selection of patients with a good prognosis. Still, it’s a significant survival benefit.
Now, there have been a number of trials and there have been meta-analyses of studies that have been performed sometimes with more than 10,000 patients. And from these trials, the median overall survival for TACE is around 19 months. This is real-life what you can expect from TACE—19 months. You can say the glass is half full or half empty. First of all, you need to reach 19 months with any other treatment you have available. But on the other hand, I think we should not, like, be overexcited about TACE. It’s still a limited time frame we can achieve with TACE. And now, having more systemic therapies available, I think it’s really critically important that we still use TACE but that we do not overuse it, and that we have a really clear focus on liver function. That would be most important—that we treat patients, but we shouldn’t deteriorate liver function with the treatment.
Ghassan K. Abou-Alfa, MD: I definitely agree on that. And, if anything, yes, we do treat with TACE until there’s no tomorrow—however, with 1 exception. We understand in Japan that you have certain decisions made, that you agreed among all the experts in Japan in regard to how many TACE and when would you stop TACE, based on what’s the frequency of the TACE. Teach us a little bit about what are your guidelines.
Masatoshi Kudo, MD, PhD: Yes. JSH, or Japan Society of Hepatology, guidelines define that TACE failure or refractoriness is when we perform repeated TACE sometimes more than 10 times. In Japan, because of the surveillance system, fewer and smaller tumors are found. So, we perform superselected TACE, even though there is a multifocal disease. Then, that way, we can obtain a nearly complete response without liver damage. So, as far as the superselected cases possible, we will repeat TACE. But sooner or later, that kind of TACE procedure will not be effective. That means that maybe first, second, third, fourth TACE, and then fifth TACE. After fifth TACE, there is some recurrence, or it does not respond well; in that case, bilobar multifocal disease. So, in that case, we cannot perform superselectively. Then the right lobe and left lobe—in other words, whole liver TACE can be performed. That way, response is low and liver damage deteriorated. So, after 2 consecutive TACE, if a new lesion or original tumor recurs 1 month later, that we define as TACE failure. At that point, even though technically, TACE is possible, we recommend switching to the next line of treatment, which means systemic therapy.
Ghassan K. Abou-Alfa, MD: That’s fascinating. Actually, if anything, we are well aware of the system in Japan that they came to agree upon, which is, like, how many TACE? How is the frequency between the TACE to make sure that patients benefit from it? Because, as we noticed, if we’re going to turn that superselective TACE into a broad TACE, that might actually be rather ineffective and might also hurt the liver per se. That’s definitely very valuable, but admittedly, we don’t have it all over.
Transcript Edited for Clarity
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