Dr Michael Morse on Managing Toxicities During HCC Treatment

Managing toxicities in the changing hepatocellular carcinoma treatment landscape is key to ensuring patients have the best possible outcomes in the front line and beyond, Michael Morse, MD, FACP, MHS, professor of medicine at Duke University School of Medicine and medical oncologist at Duke Cancer Center, explained. And as novel therapies are utilized, oncologists should educate patients on the potential toxicities of different systemic therapies.

Transcript

How do you manage toxicities when treating patients with hepatocellular carcinoma, and are there any special considerations with novel therapies?

For somebody that focuses on this area, this is a rapid learning curve, because for a long time, we've been used to managing the kinase inhibitor toxicities—the hypertension, proteinuria, hand-foot syndrome, oral lesions, diarrhea, and fatigue—and our staff has gotten pretty good at that. And we use these drugs in a lot of other cancers, so I think oncologists at large have a way of managing them. We're not perfect, and people still often need dose reductions, but we can often keep people on therapy, and that's likely to be how they're going to get the greatest benefit.

With the checkpoint blockade, the immune therapies, there's a whole new group of toxicities that we're having to consider now. Of course, we do have experience across a variety of other cancers where we're using these drugs, so I think many oncologists are comfortable with them. But we do need to educate patients that just because they go to an emergency room and have severe diarrhea, for example, that may not be the tyrosine kinase inhibitor. Diarrhea, with immune checkpoint inhibitors, they can persist, they can get quite severe, they can require hospitalization, they can be lethal. It depends, but you sometimes have to be more aggressive and think about the immune-mediated toxicities that you see differently than the toxicities that we're seeing with the tyrosine kinase inhibitors.

The other thing it's bringing up is sometimes people need to have additional testing done before they are going to start on a therapy. Immune therapies, you obviously want to take into account other comorbidities as well. Do they have underlying autoimmune disease? Have they had a transplant? Are they being considered for transplant? But with the additional drugs we're adding on—for example, an anti-VEGF antibody—that can cause bleeding as a risk. And so now we have to make sure that people are getting endoscopies done before they get that anti-VEGF antibody like bevacizumab. And then when people are on therapy, we have to be attuned to the fact that they might have a higher bleeding risk with that combination. If they're getting a dual checkpoint, they're at higher risk of getting an immune-mediated toxicity, but not so much the bleeding.

So yes, it's important to know how to manage all these—and then through multiple lines, because obviously, if people get multiple lines of therapy, they have the longest survival. And if somebody has toxicity that they're just unwilling to take another line of therapy because of concern about what happened to them before, that may be a disservice. They may benefit from something that they just don't feel that they can take. I think we also have to realize that just because somebody didn't tolerate a particular therapy does not mean they won't tolerate others, so you can certainly get multiple lines with different mechanisms of action—sometimes the same mechanism of action, but it's just a different drug. Just because you didn't tolerate one type of TKI [tyrosine kinase inhibitor], you might tolerate a different one later.