Ghassan K. Abou-Alfa, MD: As we are hearing, nowadays, in regard to local therapies, there are different options. We heard from Riad that chemoembolization and radioembolization are almost equal based on some of the data that were reported from Memorial Sloan Kettering. On the other hand, the favored approach across the world, because of level 1 evidence, is chemoembolization. We heard quite a bit about the radioembolization approach. It may be something that we didn’t touch on, but there is a certain understanding that patients with vascular involvement may be more prone for embolization as well. Then we touched on a more debatable subject.
One effort that has been brought up with regard to the use of systemic therapy is the use of sorafenib with chemoembolization. The first efforts were actually not in favor, and there was a debate saying that they waited too long until they started sorafenib after embolization. This was circumvented by other trials, among the TACE 2 study. And we saw the SPACE study. We still did not really see the benefit. And then, as Peter said, there was the advent of the approach of the checkpoint inhibitors with embolization, which is relatively new. First-reported data appear to be exciting and inviting, with regard to potential. But of course we need to further analyze it.
This leads to some questions. If we go back to sorafenib, the story was that the embolization might cause a certain angiogenic drive, exactly as a colleague has told us for years, regarding what we do to the tumor and how we excite the tumor. There was the idea that it may really intercept. On the other hand, we consider the alteration to the immune system that the embolization will do, let alone the fact that the tumor by itself is immunogenic to that environment. As such, the checkpoint inhibitors might do the job. Amit, the question is, do you think it’s going to really be about the checkpoint inhibitors, or do you think we’re going to go back to the drawing table and bring back the TKIs [tyrosine kinase inhibitors]? Maybe we’re going to put everything together—like embolization plus checkpoint inhibitors plus TKI therapy?
Amit Singal, MD: That’s an interesting question. I think this goes back to Peter’s point. You have to weigh any kind of efficacy against the toxicity. So the more and more drugs you add, the more and more toxic your combinations are going to be. I hope that we don’t end up combining all 3. I’m hoping that we do this in some kind of thoughtful fashion. Right now, with the excitement with the checkpoint inhibitors, in terms of the mechanism of why they may work, I think that would be the next-best study—to combine a checkpoint inhibitor with TACE [transcatheter arterial chemoembolization]. Then we can see how the other combinations tend to work together and go from there. But I think that if you throw the kitchen sink at an intermediate-stage tumor, you’re going to invite a lot of toxicity for, probably, little benefit.
Transcript Edited for Clarity