Update on Treatment of Advanced Liver Cancer - Episode 12
Transcript:Ghassan K. Abou-Alfa, MD: I have to admit that we all get excited, we all do clinical trials, and we’re all culprits here involved in many treatments and many clinical trials, the last of which, is a very important trial, which was reported at ASCO GI. CALGB 80802 was based on randomized data of doxorubicin plus sorafenib versus doxorubicin plus placebo at that time. There was an improvement in survival noted in regard to the doxorubicin/sorafenib that led to a large randomized phase III trial, which was the first NCI-sponsored phase III trial in HCC of doxorubicin plus sorafenib versus sorafenib. Unfortunately, that data did not reveal any improvement in survival. Quite a bit of disappointment for really a very academic, well-regimented exercise moving from a phase I to a phase II, to randomized phase II, and then to a randomized phase III, that didn’t really give us any hope in regard to the addition of doxorubicin in that setting.
However, the future is in front of us and there’s a lot going on, not necessarily in the treatment of the HCC per se, but even in supportive therapy. And, with this said, I would like to start by discussing what’s new, and what’s emerging in regard to the treatment of hepatitis C (HCV). Amit, please tell us.
Amit G. Singal, MD: I think it’s been an exciting time because the new hepatitis C treatments that we’ve seen come out are probably one of the greatest breakthroughs that we have in medicine over the last 10 to 20 years. We have a virus that we can, essentially, cure with 95% to 100% effectiveness, and this is not only seen in the large trials that have come out, but also in the clinical experience that we treat patients. These medications are expensive, but highly, highly effective. When we treat the hepatitis C and cure the hepatitis C, we see a significant reduction in the liver-related mortality, as well as the risk of HCC. In patients who do not already have cirrhosis, you can essentially almost universally prevent the progression of cirrhosis and prevent HCC. In those who have already developed cirrhosis, you have about a 75% reduction in the risk of developing future HCC as well as liver-related mortality. So, you can have a substantial benefit in reducing future HCC burden.
Ghassan K. Abou-Alfa, MD: That’s incredible. If anything, we just heard about probably one of the most important achievements in medicine in the last several years, which is that you can cure HCV by applying the antiviral therapy that we just heard about. And, in addition to that, we can definitely even consider a potential cure in patients with cirrhosis already on board. My question is, however, can you give that therapy for a patient with already established HCC?
Amit G. Singal, MD: Yes, sorry, that’s what I was going to add. I think that this is important not only for people who have not developed HCC, but also as prevention for those who have been treated for HCC. Now, in our practice, what we are doing is we are using this after curative therapy.
Ghassan K. Abou-Alfa, MD: After curative therapy. That’s very critical. Let’s talk about that.
Amit G. Singal, MD: We are treating some people while they are on the transplant list. And, if they are not eligible to be treated while on the transplant list, or have decompensated liver disease, etc., that will now allow them to be treated safely, then we will treat them post-transplant. Similarly, for anyone who’s been resected or undergone ablation with complete response, we wait about 3 months after the therapy, and then we’ll initiate them on hepatitis C therapy—once again, given the data that show that you significantly reduce the risk of future HCC developing. You can get a similar response from somebody who has chronic hepatitis B-related HCC. It’s important to also treat the underlying liver disease as it’s been associated with a reduction in HCC recurrence.
Ghassan K. Abou-Alfa, MD: Fair enough. Richard, I’m sure you’re getting that question in clinic. Patients who already have metastatic HCC, are you giving them or would you recommend treatment, or what do you discuss with your hepatologist regarding treatment of the hepatitis C?
Richard Finn, MD: I think it depends how they’re doing. We’ve had patients who have had advanced disease that seem to be doing well over months to a year. And I think, at that point, it’s a discussion you can have with the hepatologist. The question that is still unanswered is, if you treat their hepatitis C, are they going to live longer? But, at some time, you just give the patient the benefit of the doubt.
Ghassan K. Abou-Alfa, MD: Yes, I might have a little bit of a more careful opinion on that, but, nonetheless, this is a great discussion. We really don’t know, if anything, the right treatment or the right clinical trial that should be joining the proteasome inhibitors plus a sorafenib, for example, in patients with advanced HCC, and see what the outcome would be. Because, remember, that these therapies might have certain toxicities and, as such, might actually injure the liver, and that’s why we’ve got to be very, very careful with regard to that. At least I would give credit to my colleague here, Richard Finn, that maybe it’s a discussion that needs to be insured and make sure that we are approaching it in the correct way. Last word on that from Amit.
Amit G. Singal, MD: I think the key thing to keep in mind when you’re looking at this from a population standpoint is the cost. These medications are highly effective, but, unfortunately, also very expensive. So, these medications are on the order of around $50,000 to $70,000 per treatment. And, so, when you look at people who may not have a survival benefit, then you’re going to be spending a lot of money to do very little benefit.
I think that, traditionally, the way that we look at this is we will do this definitely in somebody who has a curative option. In people with localized disease that may be undergoing chemoembolization who appear to be responding, I think in those people maybe you can consider it. And people who have advanced disease who you’re talking about a median survival, that’s still around a little less than a year and maybe a little bit over a year in this select group with good response. I don’t know if you’re going to see a great benefit to doing HCV treatment in those.
Ghassan K. Abou-Alfa, MD: I try to be politically correct to my friend Richard Finn, but it seems I’m getting very, very well supported by Amit over here. I personally don’t give therapy and I don’t support therapy for HCV when there’s a patient with metastatic disease, understandably so. But there is a curative intent and, as you noticed, even they are very careful. They will wait 3 months at least before they might apply that therapy. So, something we definitely, very carefully, need to think about not only from the perspective of the patient but really from the healthcare risk, and benefit, and cost per se.
Transcript Edited for Clarity