MHCC Combination Therapies: Selection and Differentiation



Ghassan K. Abou-Alfa, MD, MBA: Let’s stick to the systemic therapy for our colleagues who are listening. Pierre, if I were to summarize what Anthony has brought up, if I were to summarize it into 3 categories, we have a checkpoint inhibitor being mostly anti—PD-1 [programmed cell death protein 1] and anti–PD-L1 [programmed death-ligand 1], plus an antiangiogenic. Then we have a checkpoint inhibitor again—anti–PD-1, anti–PD-L1 plus a TKI [tyrosine kinase inhibitor]. Lastly we have anti–PD-L1 plus anti-CTLA4. Basic question: are we talking about the same thing here? Or will there be differences in that regard, and what will be the difference?

Pierre Gholam, MD: I think only time will tell if safety and efficacy turn out in a stellar manner. One important point that we don’t often bring up but probably should is patient convenience. If all these treatments tend to be more or less equivalent in terms of safety and efficacy, my patients favor a more intermittent schedule in which they receive treatment intravenously as opposed to having to adhere to the daily rigors of taking pills. Obviously that becomes not nearly as important if there’s a differential improvement in efficacy based on hard end points like overall survival.

Are we doing the same thing, and are we targeting the same potential pathways just with different assets? You could say that, but it remains to be seen whether the outcomes in combination will end up being significant.

Ghassan K. Abou-Alfa, MD, MBA: I think from the practicality component, it’s important. Catherine, biologically this is intriguing in regard to the antiangiogenic plus the checkpoint inhibitors, TKI plus checkpoint inhibitors, or as we heard the checkpoint plus checkpoint inhibitors, like anti—PD-L1 plus anti-CTLA4.

Catherine T. Frenette, MD: They all have their own benefits. Scientifically, for instance, some of the TKIs can make some immunomodulatory changes that may help the immunotherapy work a little better.

Ghassan K. Abou-Alfa, MD, MBA: I like that. For example, the PEMBRO [pembrolizumab]—lenvatinib regimen.

Catherine T. Frenette, MD: Exactly. So that is very intriguing in terms of, is there something we can do to really boost the efficacy of the immunotherapy specifically? The dual immunotherapy checkpoint inhibition is very interesting. That is balanced, as we said, with toxicity. We just have to remember that when we’re thinking about which therapies we’re going to use, but they all have pluses and minuses.

Ghassan K. Abou-Alfa, MD, MBA: Fair enough.

Transcript Edited for Clarity

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