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Liver-Directed Therapy +/- Sorafenib in HCC

Panelists: Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center; A. Ruth He, MD, PhD, Georgetown University Medical Center; Mark W. Karwal, MD, University of Iowa Health Care; Mark H. OHara, MD, Hospital of the University of Pennsylvania; Manish R. Sharma, MD, University of Chicago; Amit Singal, MD, UT Southwestern Medical Center
Published: Friday, Sep 28, 2018



Transcript: 

Ghassan K. Abou-Alfa, MD: Ruth, we already alluded to the question of chemoembolization followed by or given along with some form of systemic therapy. I think that most of the data probably come from the use of sorafenib in that regard. What are your thoughts on that?

A. Ruth He, MD, PhD: Multiple studies have been carried to really evaluate the combination of TACE plus sorafenib. Most of the studies have been negative and have not really generated better prolonged or significant survival with the combination.

Ghassan K. Abou-Alfa, MD: Absolutely. This is very true. What Dr He is referring to is the SPACE study by Dr Lencioni. The combination of TACE plus sorafenib did not show any improvements in outcome. Definitely, in that setting, the recommendation is not to use the combination of TACE plus sorafenib. Interestingly, Amit mentioned the use of the radioembolization (ie, yttrium 90–based therapy) plus sorafenib. This study, the SORAMIC study, is still ongoing. The other studies did not work.

This really brings up a very important discussion. BCLC stage B, which we are talking about right now with locally advanced disease, and BCLC stage C, which is the start of advanced or metastatic disease—these things are not necessarily clinging to each other. If anything, I think it’s got to be more of a marriage than a divorce. This is actually something that we wrote about in an editorial in the Journal of Clinical Oncology back in 2010, which is ultimately a combination of this.

So, what is the ultimate combination? At my institution, we use bland embolization. But interestingly, when it comes to a trial that we are currently doing, using nivolumab plus embolization, we’re using chemoembolization. Manish, can you tell us a little about the role of chemotherapy and the augmentation of the effect of the checkpoint inhibitors?

Manish R. Sharma, MD: Yes. You’re thinking about radiation?

Ghassan K. Abou-Alfa, MD: Yes.

Manish R. Sharma, MD: We have definitely explored that quite a bit at our institution. SBRT, or external beam radiation, is actually an underutilized modality in hepatocellular carcinoma. There are a lot of good data showing high local control rates comparable, in many ways, to some of the liver-directed therapies that we’ve already discussed—the embolization procedures. It’s really something that can be easily combined with systemic therapy quite well. And so, we have an ongoing trial at our institution where we’re combining SBRT with immunotherapy. I think this is similar to what you guys are doing with chemoembolization. I think this is the next frontier—figuring out how we can combine liver-directed therapies, whether it be radiation or embolization with systemic therapies, to sort of enhance the effects of these therapies, assuming that we can establish safety.

Ghassan K. Abou-Alfa, MD: Absolutely. If anything, the effect of the checkpoint inhibitors will probably be maximized with other interventions. There are some data on the use of radiation and the abscopal effect. But now it’s much more evolved than that. And, of course, the other story pertains to the use of chemotherapy.

I would like to ask 1 last question regarding locally advanced disease. Mark, you have a patient with a 5-cm lesion in the liver. It definitely looks amenable to embolization. It is not amenable to surgery. The patient also has a bone lesion in vertebral body L3. What would you do? Would you give systemic therapy or embolization?

Mark W. Karwal, MD: Systemic therapy. It doesn’t do any good to change 1 flat tire when you have got 4. The patient needs systemic therapy.

Ghassan K. Abou-Alfa, MD: Great. I’m very happy to hear that. This is very important. If anything, we originally had a misperception for a patient with a small disease of the lung or a small disease of the bone. I chose bone on purpose. Based on an article that was published in the Journal of the National Comprehensive Cancer Network, the chance for bone metastases in HCC is up to 30%. For a patient with a disease like this, by all means, I totally agree with using systemic therapy. Don’t let the big thing in the liver belittle the small things that could be happening in the lung, bone, or anywhere else. Whenever we initiate any interaction to local treatment, we are going to excite the angiogenic component. This is probably going to worsen the disease. Actually, this is a real story. I heard about this from somebody. It happened here in the United States. A patient went for embolization with that same scenario. The tumor in the vertebral body grew, caused cord compression, and it was missed. This is exactly what you don’t want to do.

Transcript Edited for Clarity 

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Transcript: 

Ghassan K. Abou-Alfa, MD: Ruth, we already alluded to the question of chemoembolization followed by or given along with some form of systemic therapy. I think that most of the data probably come from the use of sorafenib in that regard. What are your thoughts on that?

A. Ruth He, MD, PhD: Multiple studies have been carried to really evaluate the combination of TACE plus sorafenib. Most of the studies have been negative and have not really generated better prolonged or significant survival with the combination.

Ghassan K. Abou-Alfa, MD: Absolutely. This is very true. What Dr He is referring to is the SPACE study by Dr Lencioni. The combination of TACE plus sorafenib did not show any improvements in outcome. Definitely, in that setting, the recommendation is not to use the combination of TACE plus sorafenib. Interestingly, Amit mentioned the use of the radioembolization (ie, yttrium 90–based therapy) plus sorafenib. This study, the SORAMIC study, is still ongoing. The other studies did not work.

This really brings up a very important discussion. BCLC stage B, which we are talking about right now with locally advanced disease, and BCLC stage C, which is the start of advanced or metastatic disease—these things are not necessarily clinging to each other. If anything, I think it’s got to be more of a marriage than a divorce. This is actually something that we wrote about in an editorial in the Journal of Clinical Oncology back in 2010, which is ultimately a combination of this.

So, what is the ultimate combination? At my institution, we use bland embolization. But interestingly, when it comes to a trial that we are currently doing, using nivolumab plus embolization, we’re using chemoembolization. Manish, can you tell us a little about the role of chemotherapy and the augmentation of the effect of the checkpoint inhibitors?

Manish R. Sharma, MD: Yes. You’re thinking about radiation?

Ghassan K. Abou-Alfa, MD: Yes.

Manish R. Sharma, MD: We have definitely explored that quite a bit at our institution. SBRT, or external beam radiation, is actually an underutilized modality in hepatocellular carcinoma. There are a lot of good data showing high local control rates comparable, in many ways, to some of the liver-directed therapies that we’ve already discussed—the embolization procedures. It’s really something that can be easily combined with systemic therapy quite well. And so, we have an ongoing trial at our institution where we’re combining SBRT with immunotherapy. I think this is similar to what you guys are doing with chemoembolization. I think this is the next frontier—figuring out how we can combine liver-directed therapies, whether it be radiation or embolization with systemic therapies, to sort of enhance the effects of these therapies, assuming that we can establish safety.

Ghassan K. Abou-Alfa, MD: Absolutely. If anything, the effect of the checkpoint inhibitors will probably be maximized with other interventions. There are some data on the use of radiation and the abscopal effect. But now it’s much more evolved than that. And, of course, the other story pertains to the use of chemotherapy.

I would like to ask 1 last question regarding locally advanced disease. Mark, you have a patient with a 5-cm lesion in the liver. It definitely looks amenable to embolization. It is not amenable to surgery. The patient also has a bone lesion in vertebral body L3. What would you do? Would you give systemic therapy or embolization?

Mark W. Karwal, MD: Systemic therapy. It doesn’t do any good to change 1 flat tire when you have got 4. The patient needs systemic therapy.

Ghassan K. Abou-Alfa, MD: Great. I’m very happy to hear that. This is very important. If anything, we originally had a misperception for a patient with a small disease of the lung or a small disease of the bone. I chose bone on purpose. Based on an article that was published in the Journal of the National Comprehensive Cancer Network, the chance for bone metastases in HCC is up to 30%. For a patient with a disease like this, by all means, I totally agree with using systemic therapy. Don’t let the big thing in the liver belittle the small things that could be happening in the lung, bone, or anywhere else. Whenever we initiate any interaction to local treatment, we are going to excite the angiogenic component. This is probably going to worsen the disease. Actually, this is a real story. I heard about this from somebody. It happened here in the United States. A patient went for embolization with that same scenario. The tumor in the vertebral body grew, caused cord compression, and it was missed. This is exactly what you don’t want to do.

Transcript Edited for Clarity 
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