Role of VEGF TKIs for Treatment of HCC

Richard S. Finn, MD: Amit, is every patient going to get ATEZO (atezolizumab)/BEV (bevacizumab)? I don’t think everybody is going to fit that profile, so there’s probably still a role for the TKIs (tyrosine kinase inhibitor) in the front line. Can you talk about that, how you choose which TKI, and who might not be the great patient for ATEZO/BEV in your opinion?

Amit Singal, MD: The IMBRAVE150 trial, as Richard mentioned, is a game changer and an exciting time for systemic therapy. All we have right now is the registration trial, which means that we have data in Child-Pugh A patients with a platelet count greater than 75,000 and who have an EGD (esophagogastroduodenoscopy) within 6 months, control of their varices, and no history of recent variceal bleeding. We don’t have safety data to extend that out to other patients.

Some of the “definite patient populations” that you would consider TKI-based therapy for are those patients where we don’t have data showing safety of ATEZO/BEV, i.e., patients with more advanced thrombocytopenia; patients with more advanced liver dysfunction; potentially Child-Pugh B7 or B8 patients; or patients with large varices or recent variceal bleed. These are patients in whom we would consider other therapies.

When we think of therapies that have data for Child-Pugh B, we think of 2 main agents. We think of sorafenib, where we have post-marketing data with GIDEON, and then we think of nivolumab, where we have a small amount of data that came out of CheckMate040 showing safety in Child-Pugh B patients. In that subgroup, you can consider 1 of those 2 agents.

There may be other patients who choose to get TKI-based therapy for other reasons. You want to say they don’t want fusions, etc, and that they want to be on oral therapy at home. In these patient subgroups, I think we’re really left with a choice of sorafenib versus lenvatinib in terms of the front line setting. Rich, you already mentioned the REFLECT trial, which compared sorafenib versus lenvatinib and showed noninferior differences in survival, as well as significant benefits in terms of secondary endpoints, including overall response rates and time to progression.

Overall, in terms of efficacy, you know the 2 are relatively similar, although, in some patients, you may want to get some benefit in terms of the response rates. In terms of safety, you see that the proportion of people who have an adverse event (AE) is similar between the 2 drugs, but the AE profile has some differences. With sorafenib, we see higher rates of hand-foot skin reaction. With lenvatinib, we see higher rates of anorexia, as well as hypertension and proteinuria.

For select patients, the way that I do it is I think through the AE profile where there may be patients who really are averse to that hand-foot skin reaction, or patients who are averse to having high blood pressure or proteinuria. I use the AE profile. Once again, there may be patients where you really want to get that objective response rate as the difference between the 2 TKI agents.

Transcript Edited for Clarity