DR O'NEIL: Unfortunately, we know relatively little. Our biggest data set is GIDEON. And if you look at the entire group of Child-Pugh B patients, the median survival — obviously, all treated with sorafenib, is 4.5 months. To me, that suggests that this is just a patient population that does poorly. And even if there’s some benefit of sorafenib, and a median survival of 4.5 months suggested, it can’t be that big a benefit.
Now, that said, the Child-Pugh B population actually is a spectrum in and of itself with scores of 7, 8 and 9 on the Child-Pugh scale. And really, the 7s behave much differently than the 9s in terms of how high are their bilirubins, how much ascites do they have, how sick are they, and they probably have, individually, different prognoses.
So I don’t tend to exclude patients from getting sorafenib just for Child B, but if a patient’s a B-9 I’m much more likely to tell them that I think the chance of them benefiting from the drug, in terms of survival, is very low compared to, say, a B-7.
DR LOVE: What about the issue of dose of sorafenib? This was mentioned already. And there are, again, a lot of questions about this. How do you approach it? How do you approach it in the older patient? If you are going to treat a Child-Pugh B, do you change the dose?
DR BEKAII-SAAB: There was a liver dysfunction study, the CALGB study, actually, that looked at various degrees of liver dysfunction.
And it is obvious that with more liver dysfunction, which, essentially, is what Child-Pugh B measures, you probably would be better off starting at a lower dose, although this was not clearly the experience in GIDEON. It seems that most patients started at the regular dose. In actual practice, it is an incredibly tough drug to give for this patient population.
And for those specific patients, at least the Child-Pugh 7 and 8, Child-Pugh 9, actually B-9 I treat like Child-Pugh C, which means they get no treatment. But for the 7 and 8, I tend to start with a lower dose, 400 milligrams, and, in fact, for some of the Child-Pugh A patients, even 200 milligrams a day and I consider escalating if they tolerate the dose well.