Hepatocellular Carcinoma: A Rapidly Evolving Treatment Landscape - Episode 8
Richard S. Finn, MD: Bleeding has become a big issue now that we have atezolizumab/bevacizumab. We never really thought of it so much with the TKIs [tyrosine kinase inhibitors], with lenvatinib or sorafenib, though theoretically it’s a VEGF class effect. Though it may be more common with bevacizumab, we thought. Does every patient with newly diagnosed liver cancer need an endoscopy? What’s your thought, Pierre? I’ll be honest, in clinic, we can write a prescription for lenvatinib or sorafenib, it gets filled within a week, and then get started on therapy. Now we’re thinking, “I want to start on atezolizumab/bevacizumab. It’s more active, and it improves survival, but is it going to take me 3 weeks to get an endoscopy?”
Pierre Gholam, MD: That would probably be one of the top 2 or 3 most asked questions when it comes to atezolizumab/bevacizumab therapy. How might one manage or mitigate the risk of bleeding in the setting of cirrhosis? An important thing to remember and consider is that the risk of having varices, or perhaps more importantly, large varices, which are those that are at-risk for bleeding, increases as the Child-Pugh score increases. Someone with Child-Pugh score C is much more likely to have large varices than patients with Child-Pugh B, and they are much more likely to have varices than patients with Child-Pugh A.
The other important point to understand, especially for a medical oncology audience, is that the risk of progression from small to intermediate to large varices per unit of time, let’s say per year, is somewhere around 7% to 10%. If you had someone who had no varices at one point, it would be very unlikely unless their disease progressed rapidly, such as is the case with uncontrolled alcohol use disorders or things like that; it would be quite likely for that patient to suddenly have large varices. There are some rational ways to address this in someone and to not delay therapy too much to mitigate the risk of bleeding.
It is certainly well established that bevacizumab can increase the risk of bleeding, and that includes life-limiting or life-threatening variceal bleeding. Would I be well-advised to screen a patient for the presence of large varices if they’ve never had screening like you’re doing, Rich? Absolutely, I would do that. If it were going to take me 3 weeks to do it? It doesn’t take me 3 weeks to do it when I do it myself.
Richard S. Finn, MD: Yes, of course. I was just saying.
Pierre Gholam, MD: I can schedule someone to have this done tomorrow, and it’ll take me 5 minutes to do it.
Richard S. Finn, MD: After their COVID-19 [coronavirus disease 2019] testing, of course.
Pierre Gholam, MD: Yes, with the COVID-19 test, sure. You’re at this prestigious medical institution, UCLA [the University of California-Los Angeles Health], you should probably not need 3 weeks to schedule this for your patients either. I would invest in the effort to do that in a patient who has never been screened or surveyed for varices. It is different for someone who may have had an endoscopy a year ago that showed no varices or small varices, so-called trace varices. I’d be comfortable starting that patient on therapy and perhaps scheduling an endoscopy at some time in the future. That would be a common-sense, rational way to approach this as opposed to getting stuck on the notion that I need to have an endoscopy right now or within 6 months to set up that procedure.
Richard S. Finn, MD: That’s a good point because getting it scheduled is variable depending on where you practice. Even still, starting 1 dose and then go on and get your endoscopy a few days later. We need to get away from this idea that bevacizumab is heparin or an anticoagulant or something with some sort of biologic effect.
Katie Kelley, MD: Can I ask a quick question for Pierre?
Pierre Gholam, MD: Sure.
Katie Kelley, MD: You mentioned the rapidly progressive liver disease. My concern in this context may be the patient who, a year ago had small varices, but now has a new main portal vein tumor thrombus and rapidly progressive portal hypertension. We in oncology have to remember those patients. Correct me and weigh in on this: those patients probably merit a new endoscopy at the decision point.
Pierre Gholam, MD: Yes. That’s an interesting wrinkle in all this. If someone has no portal vein thrombosis burden and suddenly develops a tumor thrombus, a massive portal vein thrombosis, might one expect this sudden rise in portal pressure to lead to the development of large varices? Believe it or not, the literature is not entirely clear on that. There is some indication that acute inclusion in the portal vein can perhaps, in animal models or other settings, cause a rapid rise in HVPG [hepatic venous pressure gradient] and subsequently develop varices. In patients who have had chronic liver disease with a low-flow state in the portal vein to begin with, the impact may not be as dramatic as one might think. Your point is well taken, though. Let’s say someone has no portal vein thrombosis, not even partial portal vein thrombosis, and they suddenly get the classic centripetal expansion of the portal vein with an enhancing portal vein clot. Yes, I would absolutely invest in an EGD [esophagogastroduodenoscopy] in that patient.
Transcript edited for clarity.