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Considering Adverse Events in Hepatocellular Carcinoma

Insights From: Anthony El-Khoueiry, MD, USC Keck School of Medicine; Richard Finn, MD, UCLA Geffen School of Medicine
Published: Friday, Mar 22, 2019



Transcript: 

Richard Finn, MD: That also comes up to adverse effects, right? Do you see a lot of adverse effects with the I-O [immune-oncology] agents in liver cancer? We talked about their underlying liver disease. Do you have special concerns using these drugs in a population with underlying liver diseases?

Anthony El-Khoueiry, MD: I think at a high level one can say that the adverse event profile of nivolumab and pembrolizumab in HCC [hepatocellular carcinoma] was no different than the adverse event profile of these agents in other tumor types. So that’s actually important to mention. There is particular concern about liver function, again, in patients with HCC. So one has to pay attention to AST [aspartate aminotransferase], LFT [liver function test] elevations, bilirubin elevations, and make a judgment whether this could be potentially autoimmune driven where an intervention would be needed with initiation of steroids. So, generally, what we try to do is make sure that this is not due to the elevation of the liver enzymes or bilirubin, is not due to progression or other external factors. And, if not, one has to assume that there may be an autoimmune process that’s driving this, and steroids may be indicated for grade 3 events.

Richard Finn, MD: So another reason to involve the multidisciplinary approach, not necessarily only for treatment decisions, but managing toxicity, right?

Anthony El-Khoueiry, MD: Absolutely. And also one has to watch for other known autoimmune complications with these I-O agents, which could occur in the setting of HCC as well.

Richard Finn, MD: Thyroid disease, diabetes. As long as we’re talking about toxicity, with regorafenib, I think its adverse effect profile, for those of us who have worked with sorafenib for so long, we’re probably pretty comfortable managing that. There’s a little more hypertension, but hypertension with the TKIs [tyrosine kinase inhibitors] tends to be manageable either with calcium channel blockers or ACE [angiotensin-converting enzyme] inhibitors, things like that, diuretics even for the liver population. You participated in the cabozantinib studies. Do you have any insight to that or the fact that it overlaps with sorafenib and regorafenib? It’s generally a similar adverse effect profile?

Anthony El-Khoueiry, MD: It’s largely a similar adverse effect profile. And I think the message is consistent with all these TKIs. I think practitioners have to be good at educating their patients about the potential toxicities, practice a lot of what I would refer to as maybe prevention or early intervention. You have topical urea creams for hand-foot skin reaction, education about diarrhea, diet changes, loperamide initiation.

Richard Finn, MD: You see them frequently.

Anthony El-Khoueiry, MD: I see them frequently.

Richard Finn, MD: These are oral anticancer drugs. Especially for people who aren’t used to working with these drugs, you can’t just give them a prescription and say, “I’ll see you back in 3 months.”

Anthony El-Khoueiry, MD: Absolutely.

Richard Finn, MD: They need active monitoring so early interventions can prevent them.

Transcript Edited for Clarity
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Transcript: 

Richard Finn, MD: That also comes up to adverse effects, right? Do you see a lot of adverse effects with the I-O [immune-oncology] agents in liver cancer? We talked about their underlying liver disease. Do you have special concerns using these drugs in a population with underlying liver diseases?

Anthony El-Khoueiry, MD: I think at a high level one can say that the adverse event profile of nivolumab and pembrolizumab in HCC [hepatocellular carcinoma] was no different than the adverse event profile of these agents in other tumor types. So that’s actually important to mention. There is particular concern about liver function, again, in patients with HCC. So one has to pay attention to AST [aspartate aminotransferase], LFT [liver function test] elevations, bilirubin elevations, and make a judgment whether this could be potentially autoimmune driven where an intervention would be needed with initiation of steroids. So, generally, what we try to do is make sure that this is not due to the elevation of the liver enzymes or bilirubin, is not due to progression or other external factors. And, if not, one has to assume that there may be an autoimmune process that’s driving this, and steroids may be indicated for grade 3 events.

Richard Finn, MD: So another reason to involve the multidisciplinary approach, not necessarily only for treatment decisions, but managing toxicity, right?

Anthony El-Khoueiry, MD: Absolutely. And also one has to watch for other known autoimmune complications with these I-O agents, which could occur in the setting of HCC as well.

Richard Finn, MD: Thyroid disease, diabetes. As long as we’re talking about toxicity, with regorafenib, I think its adverse effect profile, for those of us who have worked with sorafenib for so long, we’re probably pretty comfortable managing that. There’s a little more hypertension, but hypertension with the TKIs [tyrosine kinase inhibitors] tends to be manageable either with calcium channel blockers or ACE [angiotensin-converting enzyme] inhibitors, things like that, diuretics even for the liver population. You participated in the cabozantinib studies. Do you have any insight to that or the fact that it overlaps with sorafenib and regorafenib? It’s generally a similar adverse effect profile?

Anthony El-Khoueiry, MD: It’s largely a similar adverse effect profile. And I think the message is consistent with all these TKIs. I think practitioners have to be good at educating their patients about the potential toxicities, practice a lot of what I would refer to as maybe prevention or early intervention. You have topical urea creams for hand-foot skin reaction, education about diarrhea, diet changes, loperamide initiation.

Richard Finn, MD: You see them frequently.

Anthony El-Khoueiry, MD: I see them frequently.

Richard Finn, MD: These are oral anticancer drugs. Especially for people who aren’t used to working with these drugs, you can’t just give them a prescription and say, “I’ll see you back in 3 months.”

Anthony El-Khoueiry, MD: Absolutely.

Richard Finn, MD: They need active monitoring so early interventions can prevent them.

Transcript Edited for Clarity
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