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The Future of HCC Management

Insights From: Richard S. Finn, MD, Geffen School of Medicine;Arndt Vogel, MD, Hannover Medical School
Published: Friday, Dec 30, 2016


Transcript:

Richard Finn, MD:
For the past decade or so, we’ve only had one drug for liver cancer, and that’s been sorafenib. I would say there are still significant unmet needs in the frontline setting. We want to improve on this 10-month median survival. To date, we’ve tried several times, but, I think, it is possible if we have the right drug in the right patient population. With the approval of regorafenib in second line, that’s a huge step forward; again, giving patients and doctors options. But, I think, there’s still room for improvement. Hopefully, some of the ongoing studies will clarify that. We still have a large group of patients who have intermediate-stage liver cancer who do eventually progress to advanced disease. If we could figure out a drug in a population of patients with intermediate disease that could work in cooperation with chemoembolization, or adjuvant to chemoembolization, or some sequence that would improve survival, that would be great. It’s a difficult population to study. And, even in patients who are potentially cured with RFA or with surgery, since the recurrence rate is very high, to get an effective drug in the adjuvant setting would be a true advance. There’s still a lot of work to be done. Hopefully, as we see more agents that are active in the advanced setting, we’ll figure out how to use them in earlier-stage disease. Novel combinations in the frontline setting—I think a lot of us are excited to see that happen, too.

Arndt Vogel, MD: How does the future for patients with HCC look like? This is, I think, a very good and important question. If you look back, we had a couple of treatment options available, which we have used now for more than 10 to 15 years, and there was not a significant change. We had a couple of trials, many of them failed, and the treatment option did not really improve. Now, we have the first clinical trial in second line with significant improvement in overall survival. We have some interesting drugs like ramucirumab and tivantinib that could work in specific subgroups. And, with the checkpoint inhibitors, we have another group of drugs that appear to also be effective in HCC, not in all patients, but in a subgroup of patients. And, I think, this is the future of HCC. We most likely will not have 1 drug that fits all patients. Even with regorafenib, which has been positive in the RESORCE study, we have a subgroup of patients, patients who are tolerant to sorafenib, not all-comers. And, therefore, I think, in the future, first of all, the treatment might get more individualized so that we have specific clinical, maybe molecular, markers on which we decide our treatment. And the other point would be that, so far, we were not really successful to combine systemic therapy with local therapies. So, this is something with the new drugs, specifically with the checkpoint inhibitors, that we have here as a way to combine local therapies and systemic therapy. I think this is very interesting.

And, the third point is, and we have mentioned this before, when should we switch from local therapies to systemic therapies? At the moment, we only have 2 drugs available, if you are honest, but we have a lot of clinical trials. And this brings the question more into the focus, when should we stop local therapies? Specifically, if we think about studies like the BRIDGE studies, which highlighted TACE, for example, most often used in first-line treatment for patients with HCC. We do not have really clear data when to stop TACE. But now, with these more successful clinical trials, more treatment options available, and most likely approved in most countries, these are really the important points to consider.

Transcripts Edited for Clarity 
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Transcript:

Richard Finn, MD:
For the past decade or so, we’ve only had one drug for liver cancer, and that’s been sorafenib. I would say there are still significant unmet needs in the frontline setting. We want to improve on this 10-month median survival. To date, we’ve tried several times, but, I think, it is possible if we have the right drug in the right patient population. With the approval of regorafenib in second line, that’s a huge step forward; again, giving patients and doctors options. But, I think, there’s still room for improvement. Hopefully, some of the ongoing studies will clarify that. We still have a large group of patients who have intermediate-stage liver cancer who do eventually progress to advanced disease. If we could figure out a drug in a population of patients with intermediate disease that could work in cooperation with chemoembolization, or adjuvant to chemoembolization, or some sequence that would improve survival, that would be great. It’s a difficult population to study. And, even in patients who are potentially cured with RFA or with surgery, since the recurrence rate is very high, to get an effective drug in the adjuvant setting would be a true advance. There’s still a lot of work to be done. Hopefully, as we see more agents that are active in the advanced setting, we’ll figure out how to use them in earlier-stage disease. Novel combinations in the frontline setting—I think a lot of us are excited to see that happen, too.

Arndt Vogel, MD: How does the future for patients with HCC look like? This is, I think, a very good and important question. If you look back, we had a couple of treatment options available, which we have used now for more than 10 to 15 years, and there was not a significant change. We had a couple of trials, many of them failed, and the treatment option did not really improve. Now, we have the first clinical trial in second line with significant improvement in overall survival. We have some interesting drugs like ramucirumab and tivantinib that could work in specific subgroups. And, with the checkpoint inhibitors, we have another group of drugs that appear to also be effective in HCC, not in all patients, but in a subgroup of patients. And, I think, this is the future of HCC. We most likely will not have 1 drug that fits all patients. Even with regorafenib, which has been positive in the RESORCE study, we have a subgroup of patients, patients who are tolerant to sorafenib, not all-comers. And, therefore, I think, in the future, first of all, the treatment might get more individualized so that we have specific clinical, maybe molecular, markers on which we decide our treatment. And the other point would be that, so far, we were not really successful to combine systemic therapy with local therapies. So, this is something with the new drugs, specifically with the checkpoint inhibitors, that we have here as a way to combine local therapies and systemic therapy. I think this is very interesting.

And, the third point is, and we have mentioned this before, when should we switch from local therapies to systemic therapies? At the moment, we only have 2 drugs available, if you are honest, but we have a lot of clinical trials. And this brings the question more into the focus, when should we stop local therapies? Specifically, if we think about studies like the BRIDGE studies, which highlighted TACE, for example, most often used in first-line treatment for patients with HCC. We do not have really clear data when to stop TACE. But now, with these more successful clinical trials, more treatment options available, and most likely approved in most countries, these are really the important points to consider.

Transcripts Edited for Clarity 
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