Multimodality Management of Advanced Liver Cancer - Episode 8
Ghassan K. Abou-Alfa, MD, MBA: We’re going to wrap it up with a very important subject. And I’ll start with Catherine. Adjuvant therapy in regard to HCC [hepatocellular carcinoma] has not worked yet. We tried a gazillion things from the retinoic acid to the iodine radioembolization back in Hong Kong, etcetera. And sorafenib on top also was negative. So what’s the future there?
Catherine Frenette, MD, FAST, AGAF: I think that we’ve had some intriguing early studies that suggest adjuvant therapy and neoadjuvant therapy may be somewhat beneficial. Part of the concern about a TKI [tyrosine kinase inhibitor] as adjuvant therapy is the tolerability, and having a patient recover from a major surgery and then have to tolerate a TKI, I think was a little bit difficult for patients. When we’re thinking about potentially using the immune checkpoint inhibitors, they are a little bit better tolerated so that might be something that’s a little more acceptable for the patient, to give us an adjuvant therapy to mop up anything that might be left over.
Ghassan K. Abou-Alfa, MD, MBA: Fair enough. Tim, I think there are a few studies happening in regard to adjuvant therapy. I think there is an adjuvant nivolumab study and also an adjuvant durvalumab plus/minus bevacizumab study. Tell us about those.
Tim F. Greten, MD: Yes. Let me make 1 point. The bar is very high in the adjuvant setting. That’s something that we forget, if we to compare this with other tumors of the GI [gastrointestinal] tract, actually. Our surgical intervention colleagues have very good data. Patients have very good outcomes so the bar to improve this is very high.
Now, yes, coming back to your question, the immune checkpoint inhibitors are being evaluated. Again, we are following, as so often, other indications like melanoma, obviously, where this has already shown to be beneficial. And obviously, it’s an interesting question to see how to use these drugs as an adjuvant therapy. As you know, there is also the idea to use these drugs in the neoadjuvant, or perioperative, setting, and these are very early attempts. We have very few data about this, and only time will tell.
Ghassan K. Abou-Alfa, MD, MBA: Fair enough. Riccardo, back to you, and you are the expert here. TACE [transarterial chemoembolization]. How often can you do TACE?
Riccardo Lencioni, MD, FSIR, EBIR: Well, let me say that when deciding to do TACE, there are really 2 factors that need to be considered. One of course is the baseline liver function. The general status of the patient. And I think this is well understood. However, there is another factor, which sometimes is not given proper consideration, and this is the extent of the chemoembolization. This is something that we all consider for surgery, where everybody acknowledged that a small segmentectomy or subsegmentectomy is clearly a different scenario than a major hepatectomy. But the same applies also to chemoembolization. It’s not the same impact on the liver and the general condition of the patient if you truly do a good job with super or ultra-selective catherization of segmental or subsegmental arteries compared to just injecting in the right or left hepatic arteries.
The combination of these 2 factors is the main driver on the impact. And therefore, this is also the main driver for the opportunity to repeat the treatment as needed. This is extremely important, particularly because we know that this is not only a way to protect a normal liver, but also a way to maximize the anti-tumoral effect. The more you can go truly distally in the tumor-feeding artery, then of course, the higher the concentration of the drug, and the better the effect at the tumor level.
It’s a technology that has improved with advances in imaging and imaging guidance, and there must be a plan in place that has to be discussed at the tumor board, because not all the chemoembolizations are the same.
Ghassan K. Abou-Alfa, MD, MBA: Fair. Mike, back to you. I think I told you that story about how one of our colleagues one time called me and he was upset. He was not getting patients because they are stuck with Riccardo and his colleagues getting embolization after embolization. Do you feel frustrated about this? I need to give systemic therapy for this patient, but they are stuck in the TACE business.
Michael A. Morse, MD, MHS, FACP: Well, I think the point of having multidisciplinary boards provides the opportunity to discuss the appropriate patients to continue to have TACE versus having systemic therapy. Fortunately, we’re entering a realm where the combination is certainly in clinical trials as we pointed out, and this may be a historic issue and not one going forward where we have to worry about that. But for the short term, I personally feel that we sometimes see our patients have procedure after procedure, and it just seems like rapidly there’s a new lesion developing, or we’re treating people with extrahepatic disease locoregionally because the feeling is well, we need to manage the liver. We’re not so concerned about extrahepatic disease, but we should be. I think as a medical oncologist I would like to be treating these people earlier.
Ghassan K. Abou-Alfa, MD, MBA: Tim, you are the expert because if anything, you have beautiful data on some combination approaches. Act as if you are trying to be the great diplomatic mediator to bring those 2 guys together. Tell us more.
Tim F. Greten, MD: Yes. I think really the key is to have a good tumor board. You have to bring this together. And I can tell you when we first started this based on preclinical data, we tested the combination of immune checkpoint inhibitors initially with tremelimumab and then in combination with tremelimumab plus durvalumab.
One of the key moments, or special moments, that I still remember now at tumor board was one of the first patients who was treated with a transarterial chemoembolization. And just as Riccardo said, it was a very nicely done procedure that was directed to 1 side of the liver and the other side was left out. We had a follow-up scan and then the radiologist saw that the lesion in the non-TACE part of the liver actually started to regress. And our colleagues from IR [interventional radiology] were quite surprised because they noticed they had never been there. I think these are the moments where you really start to understand that, first of all, case by case, there are different scenarios, and that this combination of interventional procedures such as TACE and immune checkpoint inhibitors can be very fruitful. And that forms a base now for a number of large phase III studies being done, where this idea is being followed up, the use of TACE in combination with the immune checkpoint inhibitor. And I think that we’ll also take away a little bit of this tension, if there is any tension, about should the patient go to the interventional radiologist…?
Ghassan K. Abou-Alfa, MD, MBA: Figure of speech.
Tim F. Greten, MD: We have to do what’s best for the patient.
Transcript Edited for Clarity