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HCC: Managing Patients on Frontline Systemic Therapy

Panelists: Richard S. Finn, MD, Geffen School of Medicine; Jordi Bruix, MD, Hospital Clinic University of Barcelona; Amit Singal, MD, MSCS, UT Southwestern Medical Center; Richard H. Marshall, MD, University Medical Center New Orleans; Arndt Vogel, MD, PhD, Hanover Medical School
Published: Monday, Aug 07, 2017



Transcript:

Richard S. Finn, MD: We now have a growing number of systemic treatment options for patients. For many years, we’ve had sorafenib, which has been proven to improve survival. To Dr. Bruix’s point, one of his seminal contributions, and now, even with second-line therapies, it has been said that to get patients a second-line therapy, you need to get them a first-line therapy. In order to get a first-line therapy, we need to have a robust patient. Arndt, can you comment about first-line treatments and the management of some of the side effects?

Arndt Vogel, MD, PhD: Yes. For first-line treatment in the past 10 years, we’ve had 1 drug available: sorafenib. This was clearly a positive trial, and we had good evidence and reasons to use sorafenib. At that time, there was no second-line option.

When we use sorafenib, we have to—of course, as we do in all other tumor types—manage side effects. So, indicating specifically with sorafenib, these patients are not used to systemic therapies. They have this underlying liver disease, they might be more sensitive to side effects, and they have additional problems through the tumor and through the liver disease. These are patients that need careful monitoring. And, in general, I think there is not good systemic treatment in these patients. We have to monitor them very closely, so you can’t give them the drug and say, “Come back in 3 months.”

Richard S. Finn, MD: That’s a great point, because drugs like sorafenib, and now regorafenib and lenvatinib, are oral drugs. They are not chemotherapy. They’re molecular-targeted therapeutics, but they’re anti-cancer drugs. You don’t just say, “Take this, and I’ll see you in a few months.”

Arndt Vogel, MD, PhD: Right. These are oral drugs, so the patient is not required to come into the hospital, but still, the side effects develop. We have set up some measures meant to monitor these patients very closely. When we start treatment, we see them after 2 weeks. Then we see them again after 4 weeks. We educate them about the side effects.

Richard S. Finn, MD: Specifically, what are you looking for?

Arndt Vogel, MD, PhD: Specifically, when we start treatment with sorafenib, we have fatigue, diarrhea, and hand-foot-skin reactions. And those are side effects we really would like to control very early on. We don’t want them to develop to grade 3 or 4. It’s critically important to make adjustments to the treatment very early and also to bring the patients through the treatment. That’s why we need to see them and discuss with them what kinds of side effects might occur. We need to monitor them and, if they occur, we need to do early dose adjustments—maybe to increase the dose again once the side effects have been resolved.

Richard S. Finn, MD: So, should we start a patient at 400 mg twice a day, which is the study dose, but they may need a dose reduction? And you’re saying that if things get controlled, you would even consider going back to them?

Arndt Vogel, MD, PhD: Yes. I think there are 2 ways to start treatment. We had this discussion, also, with regorafenib—whether you start with full dose or you start with a reduced dose. I think if you start with a reduced dose, you have to keep in mind that this was not looked at in a clinical trial. And, of course, you are not allowed to forget to increase the dose if there are no side effects. If you start with the full dose, you have to do early monitoring to see whether the patients develop any symptoms that might lead to a too-early stop of treatment. I think either way is possible. In general, with sorafenib, I would start the full dose and do all the monitoring and dose adjustments once side effects occur.

Richard S. Finn, MD: We’re monitoring for toxicity, right? Another important thing is monitoring for efficacy. We know, from numerous studies, that sorafenib consistently gives us a survival benefit, which, arguably, is the most important endpoint. But it doesn’t necessarily shrink tumors.

Arndt Vogel, MD, PhD: Yes.

Richard S. Finn, MD: It’s not chemotherapy. It’s not cytotoxic. How do we know the drug is working?

Arndt Vogel, MD, PhD: This is the point we have discussed before. With sorafenib, I think we can accept stable disease as a good and proficient outcome. As long as the patient has stable disease and the tumor has not grown, I think I feel good to continue with the treatment.

Within the trial, there was a composite endpoint and there was also clinical deterioration as a marker to, maybe, continue or stop sorafenib at a later point beyond radiological findings and progression. I, personally, am not sure whether this is the right way to go. My education is more from an oncology point of view. And if you do treat beyond progression, as we do in colorectal cancer, you need to prove in a clinical trial that treatment beyond progression is meaningful—if you have a second-line treatment available, of course.

If you do not have another treatment available, I think it justifies, in some cases, to continue therapy. But, again, even with sorafenib, we might harm the liver. So, here, careful monitoring of liver function is important and would need to also be considered when we decide to treat patients beyond progression. At the moment, we have a lot of clinical trials. We have an approved second-line drug, so there is no reason not to treat beyond progression.

Richard S. Finn, MD: Frequently, do you image patients?

Arndt Vogel, MD, PhD: If they are not within a clinical trial, we do it every 3 months.

Transcript Edited for Clarity

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Transcript:

Richard S. Finn, MD: We now have a growing number of systemic treatment options for patients. For many years, we’ve had sorafenib, which has been proven to improve survival. To Dr. Bruix’s point, one of his seminal contributions, and now, even with second-line therapies, it has been said that to get patients a second-line therapy, you need to get them a first-line therapy. In order to get a first-line therapy, we need to have a robust patient. Arndt, can you comment about first-line treatments and the management of some of the side effects?

Arndt Vogel, MD, PhD: Yes. For first-line treatment in the past 10 years, we’ve had 1 drug available: sorafenib. This was clearly a positive trial, and we had good evidence and reasons to use sorafenib. At that time, there was no second-line option.

When we use sorafenib, we have to—of course, as we do in all other tumor types—manage side effects. So, indicating specifically with sorafenib, these patients are not used to systemic therapies. They have this underlying liver disease, they might be more sensitive to side effects, and they have additional problems through the tumor and through the liver disease. These are patients that need careful monitoring. And, in general, I think there is not good systemic treatment in these patients. We have to monitor them very closely, so you can’t give them the drug and say, “Come back in 3 months.”

Richard S. Finn, MD: That’s a great point, because drugs like sorafenib, and now regorafenib and lenvatinib, are oral drugs. They are not chemotherapy. They’re molecular-targeted therapeutics, but they’re anti-cancer drugs. You don’t just say, “Take this, and I’ll see you in a few months.”

Arndt Vogel, MD, PhD: Right. These are oral drugs, so the patient is not required to come into the hospital, but still, the side effects develop. We have set up some measures meant to monitor these patients very closely. When we start treatment, we see them after 2 weeks. Then we see them again after 4 weeks. We educate them about the side effects.

Richard S. Finn, MD: Specifically, what are you looking for?

Arndt Vogel, MD, PhD: Specifically, when we start treatment with sorafenib, we have fatigue, diarrhea, and hand-foot-skin reactions. And those are side effects we really would like to control very early on. We don’t want them to develop to grade 3 or 4. It’s critically important to make adjustments to the treatment very early and also to bring the patients through the treatment. That’s why we need to see them and discuss with them what kinds of side effects might occur. We need to monitor them and, if they occur, we need to do early dose adjustments—maybe to increase the dose again once the side effects have been resolved.

Richard S. Finn, MD: So, should we start a patient at 400 mg twice a day, which is the study dose, but they may need a dose reduction? And you’re saying that if things get controlled, you would even consider going back to them?

Arndt Vogel, MD, PhD: Yes. I think there are 2 ways to start treatment. We had this discussion, also, with regorafenib—whether you start with full dose or you start with a reduced dose. I think if you start with a reduced dose, you have to keep in mind that this was not looked at in a clinical trial. And, of course, you are not allowed to forget to increase the dose if there are no side effects. If you start with the full dose, you have to do early monitoring to see whether the patients develop any symptoms that might lead to a too-early stop of treatment. I think either way is possible. In general, with sorafenib, I would start the full dose and do all the monitoring and dose adjustments once side effects occur.

Richard S. Finn, MD: We’re monitoring for toxicity, right? Another important thing is monitoring for efficacy. We know, from numerous studies, that sorafenib consistently gives us a survival benefit, which, arguably, is the most important endpoint. But it doesn’t necessarily shrink tumors.

Arndt Vogel, MD, PhD: Yes.

Richard S. Finn, MD: It’s not chemotherapy. It’s not cytotoxic. How do we know the drug is working?

Arndt Vogel, MD, PhD: This is the point we have discussed before. With sorafenib, I think we can accept stable disease as a good and proficient outcome. As long as the patient has stable disease and the tumor has not grown, I think I feel good to continue with the treatment.

Within the trial, there was a composite endpoint and there was also clinical deterioration as a marker to, maybe, continue or stop sorafenib at a later point beyond radiological findings and progression. I, personally, am not sure whether this is the right way to go. My education is more from an oncology point of view. And if you do treat beyond progression, as we do in colorectal cancer, you need to prove in a clinical trial that treatment beyond progression is meaningful—if you have a second-line treatment available, of course.

If you do not have another treatment available, I think it justifies, in some cases, to continue therapy. But, again, even with sorafenib, we might harm the liver. So, here, careful monitoring of liver function is important and would need to also be considered when we decide to treat patients beyond progression. At the moment, we have a lot of clinical trials. We have an approved second-line drug, so there is no reason not to treat beyond progression.

Richard S. Finn, MD: Frequently, do you image patients?

Arndt Vogel, MD, PhD: If they are not within a clinical trial, we do it every 3 months.

Transcript Edited for Clarity
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