Updates in Frontline Treatment of Metastatic Liver Cancer - Episode 2

Initiation of Systemic Therapy for mHCC

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Richard S. Finn, MD: Riad, you participate in a lot of tumor boards, and you’re recognized around the world as an intervention radiologist. Can you talk us through the role of locoregional therapies for intermediate stage liver cancer, or those that are multifocal—confined to the liver, not invading the blood vessels?

Riad Salem, MD: You heard Amit talking about the BCLC (Barcelona Clinic Liver Cancer) staging system, and that’s something we incorporate in our tumor board. With respect to BCLC stage B specifically, one of the recommendations from the BCLC is that intermediate stage disease is treated by chemoembolization. Radioembolization is a close competitor, and it’s based on studies from 2002, showing an improvement in survival when compared with best supportive care.

My role as an interventional radiologist is to make sure we can deliver this type of treatment in a safe manner using selective injections and proper patient selection—making sure we follow patients’ imaging and liver functions, as well as making sure patients can benefit from all available treatment options. One of the things that we have traditionally been limited by is that we have locoregional therapies for BCLC stage B and few treatments after that.

Now, with the advent of positive randomized clinical trials with better survival, we have the obligation to make sure that when we apply locoregional therapy, we do it in a careful manner. We review them at MDT (multidisciplinary tumor board), and we carefully make sure that we’re able to transition the patient to another treatment option from which the patient will potentially benefit in overall survival based on all the data we’ll be talking about today.

Richard S. Finn, MD: You bring up some important points. You know, some patients with intermediate stage disease may still be curable? That’s the importance of being seen at a large center, often a transplant center, for an opinion. Even though these patients might not stay there, the cure for transplants are a moving target. Some patients with intermediate disease are amenable to being downstaged as locoregional treatment, whether radioembolization or chemoembolization—things I generally defer to my interventional radiologist to choose. Then there’s a group of patients; they’ll probably be intermediate stage disease, and locoregional treatment is their definitive treatment.

We know patients will move between stages. Maybe they’ll start intermediate and, over time, if they’re not one of those curable patients, they might become advanced, Barcelona stage C. They might even stay Barcelona stage B but max out on what you can do as an interventional radiologist. Can you talk about those 2 scenarios, that group that is definitive Barcelona stage B, and the different ways they might progress?

Riad Salem, MD: There’s a wide range of patient presentation in BCLC stage B, and that’s one of the areas of controversy and discussion, that the BCLC stage B stage should probably be subcategorized even further. There are indeed those patients that are early stage B that get some form of locoregional therapy, and they start to progress. Those patients are still technically BCLC stage B but are failing locoregional therapy, and those patients should be transitioned to systemic therapy.

There’s another group of patients, on the other spectrum of the BCLC stage B, the advanced stage Bs as we call them, who clearly have multifocal bilobar disease when applying a locoregional therapy using the principles we all agree to: selective injection, careful injection, not treating the entire lobe or the liver at the same time. That is something we believe in and we’ve observed. Many of us in the universal radiology space believe there are those Bs that are best treated using systemic therapy. That’s an area of interest for future research. Again, they’re still technically Bs but are probably best served by some form of systemic therapy.

Richard S. Finn, MD: We have the good fortune of having experts on the line. Amit, in the context of an MDT (multi-drug therapy), how do you guys decide on these issues about refractory to TACE (transarterial chemoembolization)?

Amit Singal, MD: Rich, you and Riad bring up important points here, that not all stage Bs are created equal, and not all stage Bs are treated the same. As we had mentioned, you have these early stage Bs that can be adequately and aggressively treated, and those patients can be downstaged to transplant. That is a critical point because we have to remember that surgical therapies, resection or transplant, still are for the best long-term survival. This is the way patients can survive 5, 10, 20 years. That is a very critical thing for us to get patients to when possible. I’m sure this is something with the evolving landscape as a systemic space. We’re getting to see people who go from that advanced-stage group who can actually be downstaged all the way to their early stage and can even be considered for these surgical therapies.

As we had mentioned, you are going to see people who stage shift to the right, ie, going from locoregional to advanced stage. These decisions are best made in a group where you have all those disciplines coming together, looking at the imaging together, and actually talking about what the best therapy is to give at each individual state, at each individual timepoint—not only 1 timepoint but throughout the timepoints as patients progress along that path.

The important thing with HCC (hepatocellular carcinoma) is that this isn’t just a feel-good concept. This is a concept supported by data showing that appropriate treatment is given, you give more curative therapies, and survival is prolonged in the setting of a multidisciplinary program. This should be considered the standard of care for HCC in the United States.

Richard S. Finn, MD: That’s a good segue into a lot of the advances we’re seeing coming about in the liver cancer space. For those patients who are not curable, there are some things we can generally agree on: Patients who have extrahepatic spread; patients, as Riad described, who have bilobar disease that’s multifocal; large tumors with symptoms; and patients who typically have macrovascular invasion on imaging. You know, you do a scan, and they have invasion to the main portal vein or branch thereof; those patients are unlikely to be curable. Those patients have historically been included in clinical trials with systemic treatment. Look at phase 3 data. All of them have about 20% of patients who are still at Barcelona stage B but have progressed on locoregional treatments or may not have been a candidate upfront.

Transcript Edited for Clarity