DR GROTHEY: The question comes up about “TACE versus sorafenib or TACE plus sorafenib.” And so, coming back to what TACE is. TACE is chemoembolization. It’s a locoregional therapy for patients with multifocal, nonresectable HCC, liver-dominant or liver-exclusive disease and no distant metastasis and goes back several decades and was very poorly tested in randomized trials, but kind of more K series than meta-analysis, et cetera, et cetera.
So I do believe, eventually, when you look at the bottom line, TACE does influence survival. It can be beneficial for patients who have multifocal disease. And there’s clearly some overlap in terms of the patient population that is a candidate for TACE and a candidate for sorafenib. So it really goes down to the question of sometimes who sees the patient first. What’s the flow of patients within an institution, et cetera.
And so the question came up: Does it make sense to combine TACE plus sorafenib? And actually, there’s an intriguing biological hypothesis that TACE induces hypoxia, at least in tumor tissue, which upregulates pro-angiogenic factors. So could you use a VEGF inhibitor, which sorafenib is, among other things, to block this angiogenic rebound that can occur and actually make the effect of TACE better.
Now, the question is: Should we use sorafenib or any TKI earlier or kind of start patients on sorafenib and then do an embolization and then continue sorafenib to really address this presumed rebound or kind of acceleration of pro-angiogenic factors after TACE?
This is actually being studied right now in 2 trials. One of them is led by ECOG, an Intergroup trial, 1208, which really only stops sorafenib for the time of embolization but tries to keep patients on continued sorafenib to not have this gap between TACE and initiation of sorafenib. And I think this is probably a more biologically sound approach. So the trial is currently accruing. It’s not accruing as well as we thought it would be — about a third of patients have been accrued, according to what I saw.
So I do believe this is an interesting question, TACE plus or minus sorafenib. And I can see that this turf war between interventional radiology and medical oncology for this patient population, where there’s a clear overlap in indication, will not be resolved unless we have a prospective trial.
DR LOVE: Bert, how do you approach this question in your own practice?
DR O'NEIL: I’m fortunate to, like Axel, practice in a place where we have a multidisciplinary team that evaluates these patients. So, unlike other places, we don’t have this turf battle. We all evaluate them together and make a decision.
We will use regional therapies when they’re appropriate. We tend, still, to favor chemoembolization, but some subsets of patients we’ll treat with radioembolization, such as people with portal vein thrombosis, people we can’t treat with standard embolization. At this point, I think that there are really 2 essentially negative studies of combining sorafenib and TACE at the same time or either sequentially or concurrently. There was another trial presented at the ASCO GI symposium this year called the SPACE trial, which was a Phase II study, but it was essentially negative. It didn’t provide much of a signal for sorafenib in this setting.
So, to me, if you’re going to proceed with a regional therapy strategy, you stick with that strategy until the patient has shown signs of failing that strategy, meaning they’ve progressed on therapy, before switching over to sorafenib.
DR LOVE: Can you talk a little bit more, you talked about if local therapy is indicated. In your mind, what is an indication? And specifically, do you see TACE as a way to debulk the disease?
DR O'NEIL: Yes. I mean, in some ways, TACE is very similar to giving chemotherapy.
We give chemotherapy to try and shrink disease or delay progression, and that’s essentially what TACE does. Add in this case we're just doing it in a disease that tends to remain confined to the liver.
I think the ideal candidates for TACE are people with medium-sized tumors too big to ablate, people who aren’t surgical candidates, no vascular involvement. Some of those patients can respond to TACE literally for years. So that’s really the ideal candidate. Where we start to have questions are tumors that are larger yet, say, 7-, 8-, 9-cm tumors, tumors with vascular involvement, those are a gray area. And then you start to get beyond that and I think you’re in an area where systemic therapy is more appropriate.