Managing Toxicities in Advanced HCC

Transcript:Ghassan K. Abou-Alfa, MD: However, no question, that one of our challenges is the Child-Pugh B patient, and if we can give them sorafenib or not. Richard, I would like to hear your experience on that.

Richard Finn, MD: So, this goes back to something we talked about in the context of local ablation and earlier therapies. There’s two questions: can you give it, and does it make a difference? The concern with the Child-Pugh B patients is, is there liver dysfunction? Regardless of their cancer, is their liver dysfunction what’s going to cause them to get sick and ultimately die of their disease? And I think when we’re looking at Child-Pugh B, we know they don’t do as well as Child-Pugh A. But, it is a fairly heterogeneous group of patients because Child-Pugh is not designed, as you discussed earlier, to assess patients for clinical oncology interventions. It was designed for portal systemic shunting. So, the Child-Pugh B patients are heterogeneous, and I would say if someone can come to the clinic and make follow-up appointments, then I’m comfortable giving them a trial of sorafenib. I have had patients who tolerate it well within that group of patients. I think the work you’ve done in the initial phase II looked at Child-Pugh B patients, and showed that they can tolerate it. There is an increased incidence of some of the toxicities but, again, applying the same approach to the Child-Pugh A, seeing them frequently, monitoring them, we can give them a trial of the drug.

Ghassan K. Abou-Alfa, MD: Fair enough. Yes, please go ahead, Amit.

Amit G. Singal, MD: I was going to say I think Richard hit on a major point. Child-Pugh B is a heterogeneous group, just like intermediate stage HCC is a heterogeneous group. You could have a couple lesions or you could have 50 lesions or 20 lesions. I think Child-Pugh B goes from a score of 7 to 9, and so you can have patients who are a Child-Pugh B with some mild ascites and mildly low albumen. And that patient is dramatically different than the Child-Pugh B patient who has massive ascites and a bilirubin of 2.9. I think it’s really a matter of taking a look at which side of that Child-Pugh B, because it’s a big bucket.

Richard Finn, MD: And, to add on that, what’s very important, not only in liver cancer, but other oncology indications as well—but, especially, liver cancer—is performance status. And, I think performance status and Child-Pugh are likely intimately related. But, if someone, as I said, has a performance status of 1, even though their Child-Pugh score is 8 or 7, that patient probably deserves a trial of treatment.

Ghassan K. Abou-Alfa, MD: Fair enough. To summarize that, there has been phase II data in regard to Child-Pugh reported as retrospective work in JCO on sorafenib. But later on, there was a CALGB study—60301, first author Anthony Miller from Wake Forest—that looked specifically in patients with organ dysfunction and the use of sorafenib. And that population, which was close to about 130 patients or so, had an ample number of patients with HCC, I believe 30 or more. And we noticed that bilirubin below 1.5, upper limit of normal, you pretty much give the full dose; bilirubin 1.5-3, upper limit of normal, you probably give half the dose (i.e., 400 mg daily as a total dose). For bilirubin of 3, probably there is a safety concern here not to apply the drug. And, for an albumen which is less than 2.8, probably 200 mg daily. And that definitely is a good guidance one way or the other to help you out in managing patients. But, again, it does not mean—and we heard it from the experts—that you should give up on the patients the minute they hit a Child-Pugh B. Because, first, as we heard from Dr. Singal, this might apply different things, and second, the data has shown that you probably can apply certain adjusted doses of sorafenib in that specific population.

With this said, we spoke about prognostic markers, we spoke about radiologic markers with Riccardo. Interestingly, and you recall we know this from some other data in different cancers, but, Richard, if a patient has some side effects like hand-foot syndrome or develop hypertension on sorafenib, does it mean they’re going to respond better?

Richard Finn, MD: From my experience, I would say no. I think there’s not a lot of strong literature that suggests that. There was an abstract at the GI ASCO meeting this past year that, from a single center, seemed to suggest that maybe if they did develop those toxicities, they might do better. That is more of a biomarker or a pharmacodynamic effect. It doesn’t tell us for the patient sitting in front of us, will they or will they not respond to sorafenib. So, that type of data I don’t know how useful it is. Again, based on all the clinical data we’ve had for a patient who walks into clinic with advanced disease, sorafenib is indicated. Whether or not a month later they develop hand-foot-skin reaction, that wouldn’t be a reason not to continue if they’re doing well. I mean, I think there’s probably a certain bias that the patients who don’t develop those side effects actually stay on a drug longer, and they tolerate it better. I don’t think that that type of data is ready for prime-time.

Ghassan K. Abou-Alfa, MD: If anything, these data probably just suggest to us that yes, we are eager to know how people might respond or expect them to respond. But, if anything, it reminds us that patients who have side effects, of course, we have to manage the side effects, we have to take care of them. But, at the same time, we should not give up on them as being not necessarily doing well after we manage the side effects of the treatment.

Transcript Edited for Clarity