Multimodality Management of Advanced Liver Cancer - Episode 4

Optimal Use of Second-Line TKIs in Hepatocellular Carcinoma


Ghassan K. Abou-Alfa, MD, MBA: Now, this definitely brings in a busier field all together. Catherine, you mentioned the sorafenib requirement to get regorafenib afterward. Not to put you on the spot, but regorafenib or cabozantinib?

Catherine Frenette, MD, FAST, AGAF: That’s a very good question I think everyone is debating. The cabozantinib trial did not require that sorafenib pre-tolerance, so to speak. So we do have that ability to say, “Well, OK, the patients who didn’t tolerate sorafenib were still able to be treated with cabozantinib,” and that was, I think, very helpful. It also had a little bit broader overall inclusion in terms of the advancement of the disease and underlying patient characteristics. We also have some data in terms of how to dose cabozantinib in patients who have maybe liver function that isn’t perfect. So again, we are trying to maintain that liver function through all stages and allow them to receive multiple lines of therapy. We know with cabozantinib, we need to dose reduce in those Child-Pugh B cirrhotics up front, which I think will help with tolerance to maintain therapy.

Ghassan K. Abou-Alfa, MD, MBA: Fair enough. Tim, back to you. In regard to the cabozantinib specifically, are you having any trouble in regard to tolerance with patients? Your thoughts on that?

Tim F. Greten, MD: I think to be honest, the good thing is that we learned to work with TKIs [tyrosine kinase inhibitors] in HCC [hepatocellular carcinoma] in general. And if I may, I’m going to answer your question, but let me describe a general observation we made. Sorafenib was the first TKI.

Ghassan K. Abou-Alfa, MD, MBA: Correct.

Tim F. Greten, MD: Without going into all the details, when we now look at new studies coming out in the first-line setting and use sorafenib as the comparison arm, it’s actually amazing to see how this comparison arm with the sorafenib arm is getting better, and better, which makes it obviously more difficult for the other drugs to be better than sorafenib. But what I want to say is I think the physicians who treat patients with HCC are learning more and more how to deal with the TKIs.

Coming back to your question about cabozantinib, yes, you can treat them very well. I think you have to, as it was said before, keep in mind the liver function of these patients. In our day to day practice, I think there is a relatively low threshold to reduce a dose or to start at the lower dose and then titrate up over time to increase the tolerability. But I think overall, we have learned tremendously over the past 10 years since we started treating patients with HCC with TKIs.

Ghassan K. Abou-Alfa, MD, MBA: I totally agree. It remains a rather well tolerated drug. The dose is the standard 60 mg. That’s how the study was done. If we are required to bring it down to 40 mg, it’s definitely doable, but this would be mainly because of the potential fatigue. But patients will definitely do very well on cabozantinib. And as we just heard from Tim, the experience has been rather tremendous in that regard. Back to you Mike. Child-Pugh A, Child-Pugh B, Catherine was bringing it up in regard to cabozantinib.

Michael A. Morse, MD, MHS, FACP: The whole issue of what to do with a Child-Pugh B patient is very challenging. In our practice, they make up the majority of the second-line patients. And so unfortunately, almost all clinical trials require just Child-Pugh A, so there are very few data. Of course, you did work looking at sorafenib in Child-Pugh B, and there’s some information from some of the other drugs like nivolumab. But there is surprisingly little out there. Fortunately, at least from a dosing standpoint, as Catherine pointed out, we do know there’s a recommendation of starting 40 mg in Child-Pugh B patients. I would have to admit, at that dose it is tolerated.

Ghassan K. Abou-Alfa, MD, MBA: I absolutely agree. One more thing about the cabozantinib before we move on. The study required prior sorafenib exposure. Understandably, this is what was available at that time. But interestingly, there are data and it has been shown at a few places that it can work as second- and third-line therapy with a prior exposure to sorafenib. By all means, it’s something good to have as an asset.

Transcript Edited for Clarity