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Locoregional Approaches in Hepatocellular Carcinoma

Insights From: Josep Llovet, MD, Mount Sinai School of Medicine; Riccardo Lencioni, MD, University of Miami Miller School of Medicine
Published: Wednesday, Feb 21, 2018



Transcript: 

Riccardo Lencioni, MD: There were several studies presented at ASCO GI 2018 on different uses of locoregional therapies, many new data. An interesting presentation was delivered by Masatoshi Kudo on a Japanese phase II study that combined TACE [transarterial chemoembolization] and sorafenib versus TACE plus placebo. Now, an important consideration here is that the use of TACE in Japan is different than the use of TACE in the West and in the rest of the Asia-Pacific region. This is a very important point to understand, because TACE in Japan is also used as a curative therapy in patients with early-stage HCC, which is not really the case in other areas.

This is reflected, for instance, even in the trial presented by Dr. Kudo, called the TACTICS trial, in the TTP. The TTP in the placebo arm was 13.5 months, which has more than doubled with respect to what we reported for the placebo arm of the SPACE trial, which had an identical design: TACE plus sorafenib versus TACE plus placebo. But that was a global trial with patients from the United States, Europe, and the Asia-Pacific region. So, one important point is that we are talking about a different patient population, as shown by 30% or so of patients in the TACTICS trial who were, in fact, in early stages rather than intermediate stages of HCC.

The other important point is the duration of therapy. This is probably critical. In SPACE, we’ve already seen a signal that duration of therapy was an important factor in that there’s a synergy between TACE and drugs, particularly TACE and sorafenib. So, the duration of therapy was much longer in tactics than in previous studies. This can explain the significant effect that has been shown for improving PFS and TTP. That being said, the question is still how meaningful this improvement is for overall survival. In this regard, we need the data to mature to be able to understand what the actual impact is on overall survival of this potential combination.

Another study presented on a very small sample size randomized something like 90 patients to receive radiation plus TACE versus sorafenib. We are talking about patients with advanced-stage HCC and macrovascular portal vein invasion. This study suggested that may be a signal that should be further investigated concerning the combination of radiation and TACE. Again, it’s a particularly small-scale study, and we need to see more mature data to be able to come to a conclusion that it may have an impact for the clinical decision-making process in our practice.

Josep Llovet, MD: There are other local regional therapies that are very popular in the field, particularly Y-90 embolization. This radioembolization with Y-90 has been tested in intermediate and in advanced HCC. In intermediate HCC, it has been tested mostly in phase II studies with relevant promising results, but we certainly need phase III trials comparing it to chemoembolization to understand if it has a niche in the treatment strategy for HCC.

This year, there have certainly been 2 publications assessing radioembolization versus sorafenib head to head. These 2 trials were negative. This came as a surprise, particularly for those interventional radiologists very engaged in this type of treatments, because, particularly in the United States, there are a lot of centers treating patients with Y-90. And certainly as a result of these 2 trials, we can conclude that Y-90 as a single-agent treatment is not recommended for the management of advanced HCC, and therefore, it will not be included in the guidelines. We are waiting for the 2 trials that are ongoing at this point with Y-90 plus sorafenib to understand if they have synergistic effect.

Transcript Edited for Clarity 
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Transcript: 

Riccardo Lencioni, MD: There were several studies presented at ASCO GI 2018 on different uses of locoregional therapies, many new data. An interesting presentation was delivered by Masatoshi Kudo on a Japanese phase II study that combined TACE [transarterial chemoembolization] and sorafenib versus TACE plus placebo. Now, an important consideration here is that the use of TACE in Japan is different than the use of TACE in the West and in the rest of the Asia-Pacific region. This is a very important point to understand, because TACE in Japan is also used as a curative therapy in patients with early-stage HCC, which is not really the case in other areas.

This is reflected, for instance, even in the trial presented by Dr. Kudo, called the TACTICS trial, in the TTP. The TTP in the placebo arm was 13.5 months, which has more than doubled with respect to what we reported for the placebo arm of the SPACE trial, which had an identical design: TACE plus sorafenib versus TACE plus placebo. But that was a global trial with patients from the United States, Europe, and the Asia-Pacific region. So, one important point is that we are talking about a different patient population, as shown by 30% or so of patients in the TACTICS trial who were, in fact, in early stages rather than intermediate stages of HCC.

The other important point is the duration of therapy. This is probably critical. In SPACE, we’ve already seen a signal that duration of therapy was an important factor in that there’s a synergy between TACE and drugs, particularly TACE and sorafenib. So, the duration of therapy was much longer in tactics than in previous studies. This can explain the significant effect that has been shown for improving PFS and TTP. That being said, the question is still how meaningful this improvement is for overall survival. In this regard, we need the data to mature to be able to understand what the actual impact is on overall survival of this potential combination.

Another study presented on a very small sample size randomized something like 90 patients to receive radiation plus TACE versus sorafenib. We are talking about patients with advanced-stage HCC and macrovascular portal vein invasion. This study suggested that may be a signal that should be further investigated concerning the combination of radiation and TACE. Again, it’s a particularly small-scale study, and we need to see more mature data to be able to come to a conclusion that it may have an impact for the clinical decision-making process in our practice.

Josep Llovet, MD: There are other local regional therapies that are very popular in the field, particularly Y-90 embolization. This radioembolization with Y-90 has been tested in intermediate and in advanced HCC. In intermediate HCC, it has been tested mostly in phase II studies with relevant promising results, but we certainly need phase III trials comparing it to chemoembolization to understand if it has a niche in the treatment strategy for HCC.

This year, there have certainly been 2 publications assessing radioembolization versus sorafenib head to head. These 2 trials were negative. This came as a surprise, particularly for those interventional radiologists very engaged in this type of treatments, because, particularly in the United States, there are a lot of centers treating patients with Y-90. And certainly as a result of these 2 trials, we can conclude that Y-90 as a single-agent treatment is not recommended for the management of advanced HCC, and therefore, it will not be included in the guidelines. We are waiting for the 2 trials that are ongoing at this point with Y-90 plus sorafenib to understand if they have synergistic effect.

Transcript Edited for Clarity 
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