Second-Line Treatment for Hepatocellular Carcinoma

Richard S. Finn, MD: The evolving landscape of liver cancer is just incredible to me, how fast things are changing and how well our patients have the potential to do now with all the available drugs. With the approval of lenvatinib in 2018, it left us with some unanswered questions, because at that time, we had several drugs approved in second-line, but that second-line data was all done after sorafenib. I think many of us have practiced that if a drug is approved second-line after sorafenib, and we choose lenvatinib in the front line, then we could go to cabozantinib second-line or regorafenib without necessarily having level 1 evidence that it would work, that the choice of frontline therapy, how well does that influence second-line therapy. But again, we didn’t have any strong data sets for all that. Now, we see more progress. I think the lack of data in certain scenarios does reflect progress. Now that we have atezolizumab and bevacizumab front line, essentially IO in the front line, and I think we have said that the majority of patients probably were eligible for systemic treatment. This will be the go-to regimen because of the efficacy data. But what does that do for all the molecules we have beyond that? What’s the new second line? Reena, can you put some of this into context? Certainly because many of the TKIs [tyrosine kinase inhibitors] are VEGF-plus, and even ramucirumab, which is approved second line for patients with elevated AFP is a monoclonal antibody to the VEGF receptor. What are your thoughts on how clinicians are going to integrate all this data?

Reena Salgia, MD: It’s a great question, and I think, Rich, it’s something that really remains for us all to determine what’s the new sequence or new algorithm going to look like. I certainly think that we can make some comments, one is that your point and Katie’s point earlier about the fact that there are other targets for these TKIs beyond just VEGF. When we think about second-line agents, and we look at regorafenib or cabozantinib, certainly thinking about the AXL and MET, or TAM pathways, or even FGF, there are certainly other targets beyond what atezolizumab and bevacizumab may necessarily cover entirely. I think there’s a role still for looking at those agents in the second line. Also, the question is, will some consider sorafenib or lenvatinib to be placed or shifted into being second line, even though that’s not where they were studied. And will we just shift our whole algorithm? I think the other part is the question of would you try a checkpoint inhibitor after a patient’s on atezolizumab and bevacizumab. And the question there, I think, is really what is the data?I don’t think we have that data per se, whereas in CELESTIAL, for example, we had at least a quarter of patients who have been previously on 2 lines of therapy before, and a very small percentage of patients on IO. We have a little bit of data there, but after atezo, how would you approach using another checkpoint inhibitor, I think, is a great question, and one that we can discuss as a group. I think if we look at the phase 1b RMF data, it was a little bit lackluster in terms of seeing just the single agent atezo response, and so the other options with TKIs would still be all on the table at this point.

Transcript Edited for Clarity