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HCC: Evolution of Frontline Treatment

Insights From: Arndt Vogel, MD, Hannover Medical School; Oliver Waidmann, MD, Goethe-Universitat Frankfurt am Main
Published: Wednesday, Sep 27, 2017



Transcript: 

Oliver Waidmann, MD: The standard of care is sorafenib. It has been approved for more than 10 years now, and it is an effective drug. It was more or less the first active drug for systemic treatment in HCC. However, we know that only a subset of patients really benefit from the drug. Just a subset of patients can be treated more than 4 months with the drug. The others have to stop the drug because of side effects, and I think this is the biggest issue in patients with HCC. They have a lot of side effects from sorafenib. It’s why we need some drugs that are active and also that have less side effects. And the second issue is not only side effects, but we also do not have any response rate in patients with sorafenib. The overall response rate is less than 1%, so we cannot shrink the tumor.

Arndt Vogel, MD: At the moment, I can’t clearly predict how the availability of lenvatinib will impact the treatment landscape in HCC. First of all, sorafenib is a drug that has been used for 10 years. When we look at the use of systemic therapy in HCC, the BRIDGE study is a good example. So, the BRIDGE study is not perfect, but it analyzed the use of local therapies and systemic therapies in more than 15,000 patients. And what they found is that local therapies are most often used in patients with HCC and that only 15% to 20% of patients receive systemic therapies. Even sorafenib is available and other physicians do not use systemic therapies. Now, if we have more drugs available for systemic therapies, I really hope that we shift more patients from local therapies to systemic therapies.

Overall, I think there are 2 points. More patients need to receive systemic therapies. I think, at the moment, there are even some discussions about BRIDGE. There are patients who were included in clinical trials who were not included in this study. So, there are probably more patients than this 15% to 20% who are treated with systemic therapies. But still, the numbers are very low and we need treat more patients with systemic therapies. I’m really convinced about that.

Once we shift more patients to systemic therapies, we, of course, need to decide what is the best treatment. At the moment, we have sorafenib. We most likely will get lenvatinib. But also, the immunotherapies are very much on the horizon. So, we have different opportunities available most likely in the near future, and then it will really be the challenge to decide which one is the treatment we use first, what would be the best sequence. But again, these are interesting discussions, and these are discussions I really like to make because then patients are treated with systemic therapies. And it’s more important that we shift them really from local therapies to systemic therapies.

Oliver Waidmann, MD: Lenvatinib is similar to sorafenib. It’s a multikinase inhibitor, so it’s not targeting just 1 point of the tumor cell or just 1 receptor; it’s targeting several receptors. And lenvatinib is targeting VEGF signaling, FGF signaling, KIT, and also RET, so it’s really a multikinase inhibitor and similar to sorafenib. It’s a bit different. It has a different profile. But this is the mode of action, maybe that’s why it’s working, if it’s really targeting a lot of different ways. But, of course, that’s why you also have quite a lot of side effects.

Transcript Edited for Clarity 

Brought to you in part by Eisai 
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Transcript: 

Oliver Waidmann, MD: The standard of care is sorafenib. It has been approved for more than 10 years now, and it is an effective drug. It was more or less the first active drug for systemic treatment in HCC. However, we know that only a subset of patients really benefit from the drug. Just a subset of patients can be treated more than 4 months with the drug. The others have to stop the drug because of side effects, and I think this is the biggest issue in patients with HCC. They have a lot of side effects from sorafenib. It’s why we need some drugs that are active and also that have less side effects. And the second issue is not only side effects, but we also do not have any response rate in patients with sorafenib. The overall response rate is less than 1%, so we cannot shrink the tumor.

Arndt Vogel, MD: At the moment, I can’t clearly predict how the availability of lenvatinib will impact the treatment landscape in HCC. First of all, sorafenib is a drug that has been used for 10 years. When we look at the use of systemic therapy in HCC, the BRIDGE study is a good example. So, the BRIDGE study is not perfect, but it analyzed the use of local therapies and systemic therapies in more than 15,000 patients. And what they found is that local therapies are most often used in patients with HCC and that only 15% to 20% of patients receive systemic therapies. Even sorafenib is available and other physicians do not use systemic therapies. Now, if we have more drugs available for systemic therapies, I really hope that we shift more patients from local therapies to systemic therapies.

Overall, I think there are 2 points. More patients need to receive systemic therapies. I think, at the moment, there are even some discussions about BRIDGE. There are patients who were included in clinical trials who were not included in this study. So, there are probably more patients than this 15% to 20% who are treated with systemic therapies. But still, the numbers are very low and we need treat more patients with systemic therapies. I’m really convinced about that.

Once we shift more patients to systemic therapies, we, of course, need to decide what is the best treatment. At the moment, we have sorafenib. We most likely will get lenvatinib. But also, the immunotherapies are very much on the horizon. So, we have different opportunities available most likely in the near future, and then it will really be the challenge to decide which one is the treatment we use first, what would be the best sequence. But again, these are interesting discussions, and these are discussions I really like to make because then patients are treated with systemic therapies. And it’s more important that we shift them really from local therapies to systemic therapies.

Oliver Waidmann, MD: Lenvatinib is similar to sorafenib. It’s a multikinase inhibitor, so it’s not targeting just 1 point of the tumor cell or just 1 receptor; it’s targeting several receptors. And lenvatinib is targeting VEGF signaling, FGF signaling, KIT, and also RET, so it’s really a multikinase inhibitor and similar to sorafenib. It’s a bit different. It has a different profile. But this is the mode of action, maybe that’s why it’s working, if it’s really targeting a lot of different ways. But, of course, that’s why you also have quite a lot of side effects.

Transcript Edited for Clarity 

Brought to you in part by Eisai 
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TitleExpiration DateCME Credits
35th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow® Clinical Vignette SeriesJan 31, 20192.0
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