Switching from Locoregional to Systemic Therapy in HCC

Transcript:Arndt Vogel, MD: Whether to repeat TACE is a very difficult question, I think, because we had clinical trials that were performed at a time when we did not have any good therapeutic option, specifically in respect to systemic therapy. So, at that time, there was no sorafenib and the patients generally did not receive systemic therapy. Now, we have to see all these local therapies in respect to the options we also have for systemic therapy. We really have to decide when and how long should we, and can we, repeat TACE. We do not really have the prospective data that have told us how often we should repeat TACE. What we have are a lot of clinical scores that indicate if the liver function deteriorates, if we do not see a response—for example, if we do see more hepatitis, an increase in liver transaminases—these are most likely patients that have a poor survival and they are in a poor prognostic group. And most likely, they will not benefit from repeated TACE. But as I said, these are all data based on retrospective studies and nothing has really prospectively been evaluated so far.

In general, what we say is that if the patient responds to TACE, then we can repeat the procedure, specifically if they do not have any deterioration of liver function. More difficult is if we have a stable liver disease, no deterioration in the liver function, but we also do not really see a partial response or complete response after TACE and we also do not see progressive disease. These stable-disease patients are probably the most difficult group to think about. And here, it’s really important for the future that we develop clinical trials in which we will evaluate how often should, and can, we repeat TACE and still get an overall survival benefit, and what would be the best time to stop TACE.

And also, there are some retrospective studies that indicate that switching early to systemic therapy might actually lead to better overall survival. But, again, these are only retrospective data and have never been shown in prospective trials. This is something I’m really looking forward to, that we have trials in which we compare both approaches and define clear, clear reasons to stop TACE and switch to systemic therapy compared to continuation of TACE.

The optimal time to start sorafenib is so far not well defined, and this goes back a little bit to the questions we have discussed before: how often should we repeat TACE and when should we stop TACE? What is very clear from the clinical trials, like the STORM study, is we mainly use sorafenib systemic therapy in patients with extrahepatic disease, vascular invasion, and good liver function. This is what we have been doing in the last 10 years. But now. I think the most important question—this is the question about timing—is when should we switch from TACE or Y-90 to systemic therapy and start sorafenib? And I think it’s really important that the liver function is not too impaired in our patients, that they are still in a good performance status, because these are the patients that will benefit the most. If they have poor performance status, too advanced liver disease—it could even be early Child-Pugh B cirrhosis—the benefit of sorafenib might be really small. So, I think in terms of timing, it’s important to not start too late with systemic therapy.

Transcript Edited for Clarity