Future of Unresectable HCC Management


Gastrointestinal oncology expert, Dr Ghassan K. Abou-Alfa, discusses future directions and promising novel approaches under investigation for the treatment of unresectable HCC.

Ghassan K. Abou-Alfa, MD, MBA: One might wonder: Where do you go from here? There are many things to do. Among them, the combination therapy approach is critical. We heard quite a bit about atezolizumab plus bevacizumab, which is like targeting the anti-VEGF, which is a driver to further entice the anti–PD-1 activity at the cell membrane level. But there are other, higher-level potential blockades that can further enhance that activity; among them, anti-FGF. Here is an example of the data that were presented in phase 1/2 for the combination of lenvatinib plus pembrolizumab. We’re waiting for the LEAP-002 study to see.

Ironically, that combination when we can look at anti-FGF plus anti–PD-1 has a lot of potential. Data have been shown beforehand in other diseases—I think it was in GU [genitourinary]—that a drop in Ki-67, killing the cells, increased CD3, and enhanced immunity can lead to improvement in survival, which in that phase 1b/2 was 22 months. The highest number we have for any survival in regard to HCC [hepatocellular carcinoma]. Within the context of a phase 1/2 study, you have to wait for the phase 3 trial.

Way above that, we also have the anti–CTLA-4 plus anti–PD-1 or PD-L1. It has been already tried. We have a conditional approval for ipilimumab plus nivolumab, understanding we have to be careful, because toxicity can be an issue in that regard. There’s another effort for it, which is still evaluating it in a study with only 1 dose of durvalumab to see where this might take us. For now, at least we know that the sequence of events and checkpoint inhibitors could be an important player. But our patient that we’re presenting was given lenvatinib as a second-line therapy, a checkpoint inhibitor. Pembrolizumab, which we now have full approval for in the second line, would be an appropriate option as well.

Transcript edited for clarity.

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