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Catherine T. Frenette, MD: Darren, I had mentioned earlier in this section about doing repeated TACE [transarterial chemoembolization] procedures and how it’s sometimes difficult to decide when is the right time to do a repeated TACE or another chemoembolization or another ablation is not the right thing for the patient. We need to move to systemic therapy. When are your thoughts on when is that right time?
Darren S. Sigal, MD: And like so much in medicine, it’s more of an art than a science. But there’s various factors that I think about in collaboration with you as well and the multidisciplinary team—underlying comorbidities, liver dysfunction, the status of the tumor. If additional localized therapies are possible, my preference is localized therapy because you’re not committing the patient to ongoing systemic therapy with potential toxicities. But clearly at some point, in an incurable disease, there will be progression and that progression, when local therapies are exhausted, would necessitate systemic therapy if the patient wishes additional therapy.
Currently, systemic therapy has been shown to prolong survival. First, it was shown in the SHARP study, which was the first large randomized trial showing improvement in overall survival in patients with advanced, both unresectable and extrahepatic spread, hepatocellular carcinoma using sorafenib, which is a small-molecule tyrosine kinase inhibitor. Improvement in overall survival was 10.7 months versus 7.9 months, and that’s actually a very significant improvement. And what we find is that that’s just a median improvement in overall survival, so there are clearly a lot of patients who are going to live longer than that median survival. And we’ve seen that there are certain people who can live multiple years on sorafenib alone. So, I think that at some point, and that measure may be a variable, a patient being treated exclusively with localized therapy is going to certainly transition into systemic therapy.
Catherine T. Frenette, MD: We hope. There is that patient who we see that they get so many local therapies that now their performance status and their liver function no longer allows them to get systemic therapy. And that’s really where we don’t want to take our patients to. It’s funny because for a long time, it was, “Oh, just put them on sorafenib.” It almost seemed like systemic therapy was akin to best supportive care for liver cancer. And I think that we’ve shown that. We have lots of systemic therapy options that we’re going to talk more about, but this is really an excellent treatment choice that we need to make sure that our patients have the opportunity to receive.
Darren S. Sigal, MD: Correct.
Transcript Edited for Clarity