Ghassan K. Abou-Alfa, MD, MBA: Let me take the scenario the other way around. You remember we were talking about ATEZO-BEV [atezolizumab-bevacizumab]. Now the patients come with ATEZO-BEV [atezolizumab-bevacizumab] and they do great. We can manage it. We looked at the endoscopies, and we managed everything as needed, but ultimately patients progressed.

Now the question goes back to if you have the patient, Anthony, on ATEZO-BEV [atezolizumab-bevacizumab] and they need second-line therapy. What are you going to do?

Anthony B. El-Khoueiry, MD: This is a challenging area with no data at this point. The best way to describe it is there are 2 schools of thought. One school of thought is to say, “OK, we started with ATEZO-BEV [atezolizumab-bevacizumab],” and then we reset the clock from there.

Ghassan K. Abou-Alfa, MD, MBA: You follow me on Twitter.

Anthony B. El-Khoueiry, MD: Exactly.

Ghassan K. Abou-Alfa, MD, MBA: Yeah, of course. By the way, I tweet quite a bit about HCC [hepatocellular carcinoma] @ghaboualfa.

Anthony B. El-Khoueiry, MD: As you said, then you would reset the clock and start with lenvatinib or sorafenib and continue from there with sequencing of the agents. Another school of thought says, well, let’s go from ATEZO-BEV [atezolizumab-bevacizumab] to the second- or third-line agents that have been tested already, such as CABO [cabozantinib], REGO [regorafenib], and ramucirumab.

As I alluded to earlier, it would not make sense, post ATEZO-BEV [atezolizumab-bevacizumab], to use the anti—PD-1 [programmed cell death protein 1] agents as single agents in second line.

Ghassan K. Abou-Alfa, MD, MBA: This is very intriguing, and those are 2 schools of thought. Ahmed, which school are you from?

Ahmed Kaseb, MD: I definitely would not challenge a patient who progressed on a checkpoint inhibitor, plus anti-VEGF, with a checkpoint inhibitor alone. But I thoroughly agree that the other targeted therapies are different. They have different mechanisms of action. Whoever progresses on bevacizumab, I think it is still OK to go to a tyrosine kinase inhibitor, multitargeted therapy. So there’s room for that. By the way, this is not peculiar to HCC. We’ve been through that road before in many other cancers where everything gets revamped again, as long as you’re using something with a different mechanism of action.

Ghassan K. Abou-Alfa, MD, MBA: Let me go back to what Anthony is mentioning. So ATEZO-BEV [atezolizumab-bevacizumab] in the first line. I agree with you. We’re not going to go ahead and challenge again with the checkpoint inhibitors, and this has yet to be discovered with data. But my question is, are we going backward with sorafenib? Or are we jumping to cabozantinib as second line?

Anthony B. El-Khoueiry, MD: In my practice I usually personalize this approach. There are some data from meta-analysis of multiple large phase III studies for sorafenib that showed a trend that there are benefits in hepatitis C. In hepatitis C, I usually use sorafenib. In hepatitis B there is a trend toward a better lenvatinib frontline and cabozantinib as well. So you personalize your approach in a way that is based on risk factors and demographics. I think the major transformation is going to happen when we have other combinations approved. In terms of lenvatinib, here you have checkpoint inhibitors plus TKI. You do that after ATEZO/BEV [atezolizumab-bevacizumab]. So this is going to be even more interesting to see.

Ghassan K. Abou-Alfa, MD, MBA: Peter, patients get ATEZO-BEV [atezolizumab-bevacizumab]? At the end I very much like the way Anthony described it. Do you go back to lenvatinib-sorafenib, or would you jump to second-line cabozantinib?

Pierre Gholam, MD: I have been thinking about this quite a bit in the absence of data. I would consider going back to first-line therapy options, an amnesia strategy, to basically convince yourself that nothing happened in the past however many months. And you reset the clock and start frontline therapy again.

I am not a medical oncologist. This is probably a good disclaimer to offer at this point. But in my mind it makes more sense to use established second-line treatments. Those would be cabozantinib and certainly regorafenib in the appropriate setting, as opposed to resetting the clock and using first-line therapy.

Ghassan K. Abou-Alfa, MD, MBA: I can definitely see the 2 lines.

Transcript Edited for Clarity