2021: The Year of Advances in Unresectable HCC? - Episode 2

First-line Locoregional Therapies in Advanced HCC

February 24, 2021
Amit Singal, MD, UT Southwestern Medical Center

Masatoshi Kudo, MD, PhD, Kindai University

Stephan L. Chan, MD, The Chinese University of Hong Kong

Amit Singal, MD, MS, and Masatoshi Kudo, MD, PhD, discuss the benefit/risk ratio of first-line locoregional therapies in advanced hepatocellular carcinoma.

Amit Singal, MD, MS: When we think of the debate between locoregional therapies and systemic therapy for patients with advanced stage HCC [hepatocellular carcinoma], it’s important to remember that this debate is not only informed by cohort studies, but 2 large, randomized controlled trials [RCTs] that have compared TARE [transarterial radioembolization] versus systemic therapy for patients with limited advanced stage disease. Both of those trials failed to show a benefit of radioembolization over systemic therapy for these patients with vascular invasion.

Now the interesting thing is that there are limitations to these trials, and there have been advances in both settings, not only the systemic therapy space, but also potential advances in terms of our approach with radioembolization. We’ve seen, for example, the DOSISPHERE study, which suggests a benefit of boosting the radiation dose to that tumor, which can improve responses as well as potentially improve survival for those patients. And we’ve had clear advances in terms of the systemic therapy space, not to mention inherent limitations in terms of the way radioembolization was delivered in those 2 RCTs.

When we think about this debate between locoregional therapy versus systemic therapy, although this is informed by evidence, one can argue that that evidence is maybe suboptimal in the current landscape of therapeutic options we have for these patients. I think that’s why we continue to see different treatment approaches for these patients who have vascular invasion, where the debate comes up between locoregional therapy and systemic therapy.

Now, like any debate, I think this is informed by benefits and harm. When we think of benefits, it’s informed by, for example, responses, progression-free survival [PFS], and overall survival [OS], which I think both of these therapies can offer, but it’s really the differential benefit of giving a survival benefit. Then, of course, the harm is in terms of any risk of liver injury. We know specifically whenever we do locoregional therapies, although they can be effective in terms of inducing responses, there’s always that concomitant risk of having some degree of liver injury from the chemoembolization or radioembolization in those patients.

Masatoshi Kudo, MD, PhD: There are 3 first-line agents, but the first choice of first-line regimen is atezolizumab plus bevacizumab combination therapy. There is a slight risk regarding immune-related adverse events; the risks are few in this combination, but benefit is very high. This is the first positive study that was superior to sorafenib, the standard of care for advanced HCC for nearly 10 years. After the first interim analysis, the OS hazard ratio was around 0.58 and PFS hazard ratio was 0.59, which are very good results. Patients reported that QOL [quality of life] is good and adverse events are few, so this is now the first choice of first-line agents worldwide. Most of the clinical practice guidelines for HCC were updated to show that this combination is a first-line agent.

Other agents are sorafenib and lenvatinib. With sorafenib we can obtain stable disease. We’re used to managing the adverse events, so now it’s easy to use. Response rates are very low, and there are relatively high adverse events, such as hand-foot skin reaction or diarrhea. In the case of lenvatinib, lenvatinib has a very high response rate, 40.6% by mRECIST [modified RECIST], and a very good PFS. That’s a very good point. Diarrhea or hand-foot skin reaction are less frequent than with sorafenib, but fatigue or appetite loss are slightly more frequent than with sorafenib.

We have not only physicians, but also the nurses, pharmacologists—we have a team taking care of the patients by phone or in separate rooms, taking care of the adverse events. The adverse event care team is very important for patients taking systemic therapy.

Amit Singal, MD, MS: When we think of HCC, we’re really talking about a broad landscape with multiple providers involved, ranging from hepatologists, surgical oncologists, transplant surgeons, interventional radiologists, medical oncologists, and radiation oncologists. This is the direct medical provider team, this doesn’t include other key people, such as nurses, nurse navigators, social workers, pathologists, or radiologists, who also play a key role in terms of our multidisciplinary team.

When you look at this many people being at a table or a conference deciding on the optimal treatment plan for a patient, communication is critical. This isn’t just a nice concept when we’re caring for patients with HCC, but a paradigm that has been shown to improve outcomes. There have been multiple studies that show that patients who are treated with multidisciplinary care not only have more curative treatments, better time to treatment, but most notably have improved OS. When you look at the totality of the evidence supporting multidisciplinary care, I think this isn’t just a nice concept, but should be regarded as standard of care to improve outcomes for patients with HCC.

Transcript Edited for Clarity