Expert panelists consider which therapy they would use following failure of atezolizumab + bevacizumab in advanced hepatocellular carcinoma.
Tanios Bekaii-Saab, MD: Mark, let’s say the patient you just presented had Crohn disease that’s well controlled, not even on meds at this point, you have fantastic IBD [inflammatory bowel disease], a gastroenterologist who’s willing to work with you and you decided on atezo-bev [atezolizumab/bevacizumab] in the front line and the patient progresses, what do you do?
Mark Yarchoan, MD: That’s unfortunately a data-free zone. I think many of us in that setting are using a TKI [tyrosine kinase inhibitors] in the second line after atezo-bev because there’s good confidence that VEGF agents continue to show activity after prior VEGF agents, which TKI is most appropriate in that setting. Some folks would argue that a first-line TKI is appropriate, other people would argue if they’ve had a VEGF agent, bevacizumab is not sorafenib but it’s very reasonable to use a second- line TKI such as cabo [cabozantinib]. Unfortunately, without data there’s no single right answer here. The final thing I’ll say is, I think that CTLA-4 has activity in HCC [hepatocellular carcinoma] and ipilimumab-nivolumab is something that I have used in later lines of therapy after atezo-bev.
Tanios Bekaii-Saab, MD: We’ll get back to that because I want to have that discussion, but I want to stick to immediately post atezo-bev.
Mark Yarchoan, MD: Fair enough.
Tanios Bekaii-Saab, MD: So, your preferred TKI would be?
Mark Yarchoan, MD: I think either lenvatinib or cabozantinib, and there’s no right answer.
Tanios Bekaii-Saab, MD: How do you decide?
Mark Yarchoan, MD: I’ve used both.
Tanios Bekaii-Saab, MD: OK but when you use both, I’m sure you’re not flipping a coin.
Mark Yarchoan, MD: In this patient with Crohn, my own experience is lenvatinib has a little less diarrhea, so this patient would probably get lenvatinib.
Tanios Bekaii-Saab, MD: So, if you want to avoid diarrhea, you’re thinking I’ll go with lenvatinib. Anthony, I hear a lot about how atezo-bev is now line-minus-1, which I have no idea what that means but apparently it’s coined specially in the northeast, not necessarily in Baltimore. What does that mean? Do we reset the clock, we go with atezo-bev in the minus one line and then after that we forget we had it and we move to lenvatinib? Explain this to me, I’m always intrigued by that line.
Anthony El-Khoueiry, MD: We are limited by the absence of data and by the amount of extrapolation we’re doing. If I want to be a purist again, I agree with you that I would go with an agent that has shown activity in previously systemically treated patients such as cabozantinib. Even regorafenib, you would be extrapolating because that activity was post sorafenib, specifically.
Mark Yarchoan, MD: In Sorafenib-tolerated patients, which is a unique population.
Anthony El-Khoueiry, MD: That’s why cabozantinib, at least in my practice, has gained prominence post atezo-bev. Not that I have not used sorafenib or lenvatinib occasionally, and you’re going to ask me how I choose. It’s particularities of the patient at the moment, there’s not a lot of science.
Tanios Bekaii-Saab, MD: I agree with the two of you. If everything we do was just pure science, it’s boring. The art of medicine is real here, it’s how you apply the science. Cabozantinib would be your preferred agent. What dose do you typically start with?
Anthony El-Khoueiry, MD: In patients who have good performance status, good liver function, I’m starting at the full dose of 60 mg.
Tanios Bekaii-Saab, MD: You do?
Anthony El-Khoueiry, MD: Yes.
Tanios Bekaii-Saab, MD: Mark?
Mark Yarchoan, MD: Me too.
Tanios Bekaii-Saab, MD: Pierre?
Pierre Gholam, MD: I don’t but I tend to have patients who have Child-Pugh A that’s flirting with Child-Pugh B where drug availability is known to be higher and where the package insert to some extent recommends lower therapy, so I do tend to start with 40 mg.
Tanios Bekaii-Saab, MD: You start with 40 mg. Arndt?
Arndt Vogel, MD: I start with both 40 mg and 60 mg.
Tanios Bekaii-Saab, MD: What drives the decision?
Arndt Vogel, MD: Gut feeling. I don’t know. It’s difficult.
Tanios Bekaii-Saab, MD: The art or Arndt.
Pierre Gholam, MD: I would say to your point, about this line minus one. I’ve heard this mentioned many times and I call this the amnesia strategy. Basically, you treat somebody and say, I don’t know what happened, did we just treat the patient? Let’s start from scratch. I find that to be somewhat unscientific. I don’t know if that’s accurate but I find that to be internally inconsistent, I guess, is the best way to describe.
Tanios Bekaii-Saab, MD: It’s make-believe stuff.
Transcript edited for clarity.