Hepatocellular Carcinoma Treatment Advances - Episode 2

Case 1: Role of TARE in Unresectable Hepatocellular Carcinoma

, , ,

Expert perspectives on the role of transarterial radioembolization in unresectable hepatocellular carcinoma following FDA approval.


Ghassan K. Abou-Alfa, MD: Going back to our patient, a 60-year-old man who is Asian has hepatitis B and a tumor in multiple sites. The question is, how can we treat the patient? Dr Salem, you’ve got the story. Teach us.

Riad Salem, MD, MBA: If you think about what this patient received, he received 1 of the major arterial therapies, the locoregional therapies or chemoembolization, which involves accessing the hepatic artery via the groin or the risk, placing a catheter and injecting various combinations of chemotherapeutics. That’s still a little controversial. The idea is that you instill a high dose of chemotherapy and slow down the blood flow by injecting some particles, effectively causing ischemic necrosis, chemical necrosis, etc, as a mode of treatment. It’s the gold standard for BCLC [Barcelona Clinic Liver Cancer] B disease. This person had C disease, but it was based only on performance status, so I can understand why chemoembolization was performed. Effectively, it’s a method of trying to control the disease, get a response, and maybe even downstage in some settings and, obviously, prolong life.

Ghassan K. Abou-Alfa, MD: Perfect. Along that line, Dr Salem, I’m going to put on the screen the FDA approval of TARE [transarterial radioembolization]. Tell us a little more about that.

Riad Salem, MD, MBA: As I was mentioning, chemoembolization is in the family of the arterial LRTs [locoregional therapies]. In the family is gland embolization and also radioembolization. I used to say that’s a relative newcomer, but I don’t think it’s a newcomer anymore; it’s been around for about 15 years. The technical principle is the same: you access the hepatic artery. But in this case, instead of injecting some chemotherapeutic or particle that will starve the tumor, you’re injecting a very high-dose radiotherapy. That basically means that the activity and the dose you can give in that area is very localized. It’s focused, it’s surgically precise, and it’s very well tolerated because you’re effectively radiating a very small portion of the liver where the tumor is held within that vascular territory. The biggest advantage, if you think about TARE over chemoembolization, is probably the adverse event profile. It’s very well tolerated, it’s done on an outpatient basis, and the response rate is very high. The quality of life is clearly 1 reason why the development of TARE was advocated.

Ghassan K. Abou-Alfa, MD: That’s very important information. I especially like that you brought up this last point because we all have to remember that the approval for procedural interventions is totally different from the approval for therapeutics. As Dr Salem just discussed, it’s about the safety component, or at least the effectiveness of it. It’s not necessarily required to have a randomization or a comparison. That’s what differs from what we do in systemic therapy, which we’re going to talk about in a second. Before we go there, we’ll go to Dr Yarchoan. Mark, have you seen any change in regard to the use of TARE with this approval, compared with TACE [transarterial chemoembolization], which has been the standard for more than 20 years?

Mark Yarchoan, MD: As a medical oncologist, I often defer decisions about best local therapy to others at our multidisciplinary tumor board. It’s wonderful to have this option; clearly some end points appear to be better with TARE. It’s important to remember that the LEGACY study was not a randomized study; it showed very nice local control rates. It did seem like patients did better if they went on to surgery, which suggests that maybe the pathologic response rates are not perfect with this modality. But we’re seeing more use of TARE, and it’s great to have this option.

Ghassan K. Abou-Alfa, MD: Thanks so much for that, Mark. Dr Singal, I have a question for you as well. Within the context of TARE and TACE, especially TARE, please tell us about the hepatology concerns and perspective. Of course, you can add what you like.

Amit Singal, MD: There are a couple of things that I’d add. As we had said, TARE has been around for a long time. Even though the approval just happened, you’ve seen use of TARE in many academic centers for years. As Mark was saying, you see some increase. I don’t think it went from 5% to 50%. It’s worth putting in perspective that this has been a long road. We point to the LEGACY study, but LEGACY was the straw that broke the camel’s back in terms of getting this through the door. It wasn’t just 1 study. It wasn’t like SHARP, and it wasn’t like IMbrave150 in terms of it being 1 trial and then it happens. There have been years of investigation showing that TARE is safe and effective, and much was led by Riad in the Northwestern group. You’ve seen slow adoption of this over many years. To Riad’s point, this is because of longer time to progression and better tolerance but also a higher safety profile.

Compared with chemoembolization, where you see postembolization syndrome, you can see the LFTs [liver function tests] increase in many patients. With TARE, you can be highly selective. You can do a radiation segmentectomy. You can do this very safely. From a hepatologic standpoint, you can do this with less degradation in liver function over time if done in an expert and selective manner. From a hepatology perspective, in well-selected patients, when done by experts, it’s a very well tolerated therapy. It’s important not to expand use to a broad selection of patients just because it’s well tolerated in general. If patients are a Child-Pugh B9, have uncontrolled ascites, uncontrolled encephalopathy, a large shunt fraction, etc, then they shouldn’t undergo radioembolization. Patient selection is important. This is a very helpful therapy for us to have in our armamentarium, but it’s not like it went from 5% to 50%. This has been increasingly adopted over time.

Ghassan K. Abou-Alfa, MD: Thanks so much for that, Dr Singal.

Transcript edited for clarity.