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Sequencing With Cabozantinib in Advanced HCC

Panelists: Ghassan K. Abou-Alfa, MD, Weill Cornell Medical College; Peter Galle, MD, PhD Johannes Gutenberg University, Mainz; Riad Salem, MD, Northwestern University; Amit Singal, MD UT Southwestern Medical Center
Published: Thursday, Jan 03, 2019



Transcript: 

Ghassan K. Abou-Alfa, MD: I’ll start here with the story of the c-Met inhibition. If you recall, c-Met inhibition was actually something that was very hot after sorafenib in 2007, as we heard from Peter. Then there was a lot of excitement about c-Met. Tivantinib came into play. Actually, the tivantinib randomized trial was negative, while the cabozantinib data was positive. Amit, why?

Amit Singal, MD: I think there are a couple of things that come up. The first is that tivantinib probably was not as selective of a c-Met inhibitor as we thought it was going to be. The second is that cabozantinib probably actually hits c-Met as well as some other pathways. That may be part of the reason why this is positive. But at the end of the day, it’s nice because cabozantinib adds another therapy to the list of the options that we can use as second-line therapy.

Ghassan K. Abou-Alfa, MD: I totally agree. If anything, the phase II trial suggested that the patients who will benefit the most from the outcomes are the ones who have 50% 3+ to 4+ expression of c-Met activity on their tumor immunostains. As such, it was maybe overunderstood or overinterpreted that tivantinib, at the end of the day, is a c-Met inhibitor, but it’s a tyrosine kinase inhibitor.

Amit mentioned that cabozantinib is really multi-targeted. Actually, both are multi-targeted options. As such, interestingly, probably when we did the cabozantinib study that published in the New England Journal of Medicine back in July, we said we would like to have it for every patient. There was actually a discussion with the sponsor. We pushed for taking the study and offering this drug for everybody, regardless of c-Met expression. We didn’t know how much c-Met expression was needed and how many of the other targets, as Amit mentioned, were necessary, per se. The sponsor really contributed to ensure that cabozantinib will carry on. And, of course, we ended up with a positive study.

Transcript Edited for Clarity

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Transcript: 

Ghassan K. Abou-Alfa, MD: I’ll start here with the story of the c-Met inhibition. If you recall, c-Met inhibition was actually something that was very hot after sorafenib in 2007, as we heard from Peter. Then there was a lot of excitement about c-Met. Tivantinib came into play. Actually, the tivantinib randomized trial was negative, while the cabozantinib data was positive. Amit, why?

Amit Singal, MD: I think there are a couple of things that come up. The first is that tivantinib probably was not as selective of a c-Met inhibitor as we thought it was going to be. The second is that cabozantinib probably actually hits c-Met as well as some other pathways. That may be part of the reason why this is positive. But at the end of the day, it’s nice because cabozantinib adds another therapy to the list of the options that we can use as second-line therapy.

Ghassan K. Abou-Alfa, MD: I totally agree. If anything, the phase II trial suggested that the patients who will benefit the most from the outcomes are the ones who have 50% 3+ to 4+ expression of c-Met activity on their tumor immunostains. As such, it was maybe overunderstood or overinterpreted that tivantinib, at the end of the day, is a c-Met inhibitor, but it’s a tyrosine kinase inhibitor.

Amit mentioned that cabozantinib is really multi-targeted. Actually, both are multi-targeted options. As such, interestingly, probably when we did the cabozantinib study that published in the New England Journal of Medicine back in July, we said we would like to have it for every patient. There was actually a discussion with the sponsor. We pushed for taking the study and offering this drug for everybody, regardless of c-Met expression. We didn’t know how much c-Met expression was needed and how many of the other targets, as Amit mentioned, were necessary, per se. The sponsor really contributed to ensure that cabozantinib will carry on. And, of course, we ended up with a positive study.

Transcript Edited for Clarity
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