Hepatocellular Carcinoma: Practical Implications of Emerging Data - Episode 12

Regorafenib or Cabozantinib for Second-Line HCC

, , , , ,


Richard S. Finn, MD: You mention the single-agent tremelimumab data. I think a study that many of us have overlooked that the first checkpoint inhibitor looked at in liver cancer was Bruno Sangro’s study with tremelimumab from several years go. There were some toxicity issues at that time, which I think now we might not get so concerned about. But at the time, we’re with our thinking, there were some issues with hepatitis and transaminitis. Katie, there’s RESORCE, there’s CELESTIAL. Tony introduced this idea of we’re going to these drugs now. What are your thoughts in the context of the data that we have from RESORCE and CELESTIAL and incorporating that into our current mindset?

R. Kate Kelley, MD: I think looking specifically at the regorafenib and cabozantinib choice in a second-line TKI context, I do think that it’s important to remember the regorafenib resource eligibility criterion of--requirement of a meaningful dose of sorafenib, at least 400 milligrams per day for 20 out of the last 28 days. I think we shouldn’t discount this key inclusion criteria because it does bear on patients’ risk of toxicity as well as potentially their susceptibility to that target pathway. I tend to use regorafenib really in patients who have had prior sorafenib, though again, I think there are cases where we might extrapolate to a different TKI. But I think that’s an extrapolation. I think in patients who haven’t had prior sorafenib, cabozantinib has the best level one evidence for its use in the second-line context. I think there’s also intriguing flexibility for cabozantinib in that the phase 3 trial included second- and third-line patients and patients with prior nivolumab, for example, so patients with prior IO therapy were included, admittedly a small subset. But their outcomes appeared to track with the overall population in a report from the post-nivolumab and post-sorafenib third-line population that was presented at the EASL Liver Cancer Summit this year in 2020. So, I think in that context, regorafenib is a drug best for patients who have had prior sorafenib. Cabozantinib is more flexible in the second- or third-line context, as well as a subset of patients with prior IO.

Transcript Edited for Clarity