Hepatocellular Carcinoma: A Rapidly Evolving Treatment Landscape - Episode 4

The TACE Approach for Intermediate-Stage Disease

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Richard S. Finn, MD: That’s a good transition into the approach for the intermediate group, which is a large group of patients. These are patients who have liver-confined disease and well-preserved liver function. Historically, local-regional treatments were the backbone. Peter, you’ve been very active in this space. Can you give us some background about the ideal TACE [transarterial chemoembolization] patient? It is important to recognize that TACE is not curative and that we are transitioning those patients to the next step in their treatment.

Peter Galle, MD: The situation in the intermediate stage is a peculiar 1. Let’s go 20 years back, which was when TACE was defined. There have been many trials that have not been able to demonstrate the beneficial effect of TACE. We then had 2 randomized controlled trials and a meta-analysis providing the background for TACE as the standard of care in patients in the intermediate stage. Why were they successful? First of all, at that time they had no competitor. There was no systemic therapy around.

This is something we should not forget: They were running against nothing. The trials were then positive. There were 2 trials because they were concentrating on a very recused tumor burden and on patients with sufficiently good liver function. They selected very carefully, and in this particular setting, the efficacy of TACE was demonstrated. What is happening afterward is that TACE is spread out. Everybody gets TACE, even patients with very large tumors, which are precisely those who have never been tested in clinical trials and those with poor liver function. In addition, what we have in these days is an armamentarium of many systemic therapeutic options. We have to reconsider whether TACE is the appropriate therapy, and we still have to consider to whom TACE is and is not applied.

What has happened has been nicely demonstrated in noninterventional trials, such as the BRIDGE trial. It was interesting to see that in a time when the standard of care in advanced-stage disease was defined by sorafenib. With the BRIDGE trial, which was a worldwide observational trial, it was becoming obvious that most patients—even those with advanced-stage disease—were treated by TACE. The availability and the lessons learned 20 years ago were being maintained, and that needs to be challenged today. I’m not saying that there is nobody who, in a perfect way, is suited for TACE. There are still patients suited for TACE: those with a limited tumor burden, and what should also not be neglected are cases where the tumor is accessible. If there is a nicely feeding artery and superselective approach, then this is a good patient for TACE.

If it is a diffuse, large tumor, and if this is not superselectively targetable, and if this is coming at the price of loss of liver function, this is precisely why we have to stop or never get started. In a good patient progressing on TACE or not benefiting from TACE, we need to make decisions in times of availability of systemic therapy. If there is no objective response, let’s say after 2 cycles of TACE in a situation where TACE can be appropriately done, then we need to switch. This is where the multidisciplinary team steps in. This is exactly what we all have to discuss: What is the best measure? What is the best therapeutic option for the patient? How can we switch on time?

That has been neglected, but I’m happy to see that, in the field, the term overexhaustive TACE is being discussed. Experts are acknowledging more and more that TACE is not for everybody and that it is time to end our endless cycles. Systemic therapy needs to define its role, and we will see next year’s trials challenging TACE in terms of intermediate-stage treatment, and systemic therapy will shift the BCLC [Barcelona Clinic Liver Cancer] scheme to the left.

Richard S. Finn, MD: You bring up some important points. One thing to remember is that, with liver cancer, you can have advanced liver cancer or someone who is appropriate for systemic treatment even though they don’t have extrahepatic spread, even though they don’t have metastases. There can be disease within the liver that makes a patient a candidate for systemic treatment. That would mean vascular invasion, meaning the tumors invading blood vessels. That’s a marker of patients who don’t do well with local-regional treatment. As you had commented, these are patients who have repeated procedures, and we’re not controlling their tumor.

Every time you reimage them, they still have residual tumor or tumor that is progressing despite repeated TACE. That’s when we should be bringing these cases to the multidisciplinary team. Before we had systemic treatments that were really improving survival, TACE filled that void. We had nothing else to offer patients. In 2008, sorafenib was approved vs placebo; it improves survival without a significant response rate. Even with that data, it still took time to convince multidisciplinary teams that systemic treatment plays a role in the management of patients who progress on TACE. For that matter, some centers use radioembolization or Y 90, but the issues are the same: These aren’t curative approaches. Patients will progress.

Transcript edited for clarity.