Hepatocellular Carcinoma: Switching to Systemic Therapy
Insights From: R. Kate Kelley, MD, UCSF Helen Diller Family Comprehensive Cancer Center; Josep Llovet, MD, PhD, Icahn School of Medicine at Mount Sinai; Masatoshi Kudo, MD, PhD, Kindai University; Arndt Vogel, MD, PhD, Hannover Medical School
Josep Llovet, MD, PhD: There was always a question on how many treatments a patient should receive or when we should have a signal to switch the patient to systemic therapies, and this has been in the field for a while. So, when you check the trials, the phase III trials with assessing chemoembolization, at the end, the median number of sessions is 2.3, 2.5, 2.8, 3—so it’s between 2 and 3. It’s not that you are thinking about 5 treatments, 6 treatments; it’s either 2 or 3 treatments. This is the median number of treatments in the trials, and this is the reality. So beyond that, generally, you are not providing benefit to the patient. If you don’t get the benefit in 2 or 3 treatments, this is over.
The more difficult question is when to switch to systemic therapy. And this in the period of time where only sorafenib was in the field; then, certainly, the physicians were pushing a lot of chemoembolization. And when the patient was at a truly advanced stage, then they switched to sorafenib. And there was a need to start sorafenib early on, but this was not happening. Now I think this will be a natural thing, because you have 6 potential treatments that are effective. So, therefore, physicians are more comfortable switching to systemic therapy because you have frontline lenvatinib/sorafenib, then you’re moving to second-line regorafenib, then you always may have checkpoint inhibitors. So the physician will be more comfortable offering different options to the patients, and then the switch that generally should happen when there is no response at all or progression of the disease will happen early on—I envision that.
Arndt Vogel, MD, PhD: I think there are different triggers for systemic therapies. First of all, it depends on the tumor burden. If you have big tumors, bulky disease, vascular infiltration, extrahepatic disease, they would all trigger systemic therapies right away. In contrast, if you have smaller tumors and if these are candidates that are in BCLC [Barcelona clinic liver cancer] stage B, we usually would start with local therapy such as TACE [transarterial chemoembolization]. And then the question is, how long can we do it and how often can we repeat TACE right now, then? And I think this is a very important point, because in the past—and what we are doing in general in oncology—what we would do is accept stable disease as an outcome that is sufficient. But this is different for local therapy such as TACE in HCC, because with all these therapies we are applying, we can also damage the liver and we can deteriorate liver function.
So we now have some data that patients that respond to TACE have a very good outcome. In contrast, if they have only stable disease and if they do not have deep responses after, for example, 2 TACE treatments, I think this should be a trigger to consider systemic therapies, and these patients should not be treated repeatedly with TACE or other local therapies such as Y90.
Masatoshi Kudo, MD, PhD: Metastatic disease, which is an extrahepatic spread, means locoregional therapy is not effective. So as soon as there’s metastatic disease or metastatic disease diagnosis, we introduce systemic therapy.