Patient Profile 2: A 70-Year-Old Man With Advanced HCC Treated With Durvalumab + Tremelimumab

Focusing on a second patient profile of advanced hepatocellular carcinoma, panelists consider the role of first-line tremelimumab + durvalumab.


Josep Llovet, MD: Let’s move to the second case. Kate?

Katie Kelley, MD: This patient came to me as a 70-year-old man. His weight was 68 kg, and he had past medical history notable for hepatitis C, which had been treated with antiviral therapy. He had cirrhosis with portal hypertension and a very large gastric varix—up to 2.5 cm—that was not amenable to gluing based on its size. He had some portal gastropathy. His baseline platelets were around 90,000 per mm3, and he also had some hypertension. He’d had 2 prior TACE [transarterial chemoembolization] treatments for multifocal [lesions], maybe 2 or 3 HCC [hepatocellular carcinoma] lesions.

When I met him, he’d had several LI-RADS [Liver Imaging Reporting and Data System]: 5 lesions in the liver, including 3 that were radiographically diagnosed. He’d also had extrahepatic disease in multiple metastatic lymph nodes that were measurable. We eventually did a biopsy to confirm HCC. His AFP [alpha-fetoprotein] was 889 ng/mL. He was a BCLC [Barcelona Clinic Liver Cancer] stage C and Child-Pugh A6 with portal hypertension. In this a picture you can see the TACE site in the middle and on either side. He had 2 areas of HCC recurrence with enhancement in washout. And here’s a picture of 1 of his lymph nodes with some central necrosis. This is pretreatment. At the time, this was before IMbrave150, but we had the option of a clinical trial of the STRIDE regimen, including a single dose of tremelimumab, which he received 300 mg times 1 followed by continuous durvalumab, 1500 mg every 4 weeks following the STRIDE regimen.

We can see at baseline that his liver tests were pretty stable. I mentioned the baseline thrombocytopenia grade 1 and the AFP. That’s when he started first-line [therapy]. You can see the AFP curve and then, within 1 month, his dramatic AFP drop. It went from 880 ng/mL to normal, and his AFP has remained less than 2 ng/mL since then. Early in treatment, he did have some adverse effects from immunotherapy. He had pronounced pruritus. We had to use gabapentin and some off-label treatments to deal with his itching at night. It was problematic for sleep, but there was minimal rash, patchy rash, grade 1 at most. That resolved after about 4 months. Bear in mind, he had just gotten tremelimumab on day 1 during the first treatment. That resolved after about 4 months.

Here’s what his imaging did. His AFP had normalized within the first month, and he had imaging after 2 months that showed a PR [partial response], and by 4 months it was a complete response [CR]. The lymph nodes were less than 1 cm in long dimension, and the tumors in the liver quickly became undetectable and nonenhancing. That was over 3 years ago. At month 36, which was this past April, we had a talk about how long to continue treatment. We decided based on the constellation of data from other immune checkpoint inhibitors and other tumor types that we would stop treatment after 3 years and watch him closely. Since then, he remains disease-free.

Josep Llovet, MD: Wow. That’s a very impressive case. You have 1 minute to challenge that, Andrea.

Andrea Casadei-Gardini, MD: This is an important case because in patients with large gastric varices, it’s possible to treat the patient with immunotherapy after the result of the … trial. We see a very good response with durvalumab. A longer response is typical of the patients on immunotherapy.

Josep Llovet, MD: Absolutely. Amit?

Amit Singal, MD: The interesting thing is that we always talk about esophageal varices, but the gastric varices are probably more scary. When you look at those bad bleeding events, they’re often gastric varices. For this type of thing, we have to make sure we think about that as well. You talked about not being amenable to glue—we do glue in very few cases. It’s something you can consider in some of these cases, but these gastric varices are the scary part of the bevacizumab. We’re thinking of that as well, in terms of a contraindication.

Not to say “transplant for everything,” but you’ve had a guy who’s responded very well. He started with metastatic disease, but you’re at an aggressive transplant center. Have you guys thought about referring this guy for a transplant evaluation? He would need a living donor, etc, but this case highlights how the exciting stuff you see with I/O [immuno-oncology] will bring in new questions.

Katie Kelley, MD: To what end? To play devil’s advocate, that’s my question. He’s got compensated Child-Pugh A6 liver disease. He had metastatic disease. I don’t if I’d want to immunosuppress him. He doesn’t have an indication for transplant without HCC. If we presume that there’s obviously a risk of second HCC, that’s not a transplant indication. He doesn’t have a good indication for transplant other than the prior HCC.

Amit Singal, MD: The downstaging.

Katie Kelley, MD: But then we have metastatic disease. If we immunosuppress him and it comes back…

Arndt Vogel, MD: You have the risk of rejection, right? I agree that it’s an interesting thought.

Amit Singal, MD: These are the cases that are going to present. We have a patient who once again, like your patient, had metastatic disease. He has a complete response for 3 years; he’s decompensated. Many of us feel—I don’t want to say comfortable, but you’re starting to see patients who get treated with I/O, with vascular invasion, where centers are thinking about listing them. The data have come out of Mount Sinai [Health System in New York, New York], in terms of at least some short-term safety in patients who received I/O product transplant. You’re going to start having these questions. From an oncology community perspective, you always have to ask if this patient needs to be referred for this multidisciplinary discussion or at least transplant consideration. These tough discussions are going to be happening in expert centers.

Katie Kelley, MD: With our long-term follow-up data of these CR patients, we’ll need to figure out the appropriate window of time. We’ve done transplant in 1 patient who had a CR for 5 years, and we consider that long enough. That was after nivolumab, and he just got transplanted. But what’s the window of time?

Amit Singal, MD: We’re listing our first patient with metastatic disease…

Katie Kelley, MD: That was metastatic.

Amit Singal, MD: Who responded to I/O. It just listed, so we don’t have any post-transplant outcomes, but this is going to be the fascinating thing that as a field we have to figure out.

Arndt Vogel, MD: Our first patient was transplanted after immunotherapy with a severe rejection and died from rejection. If you have a case where it works, you’re excited. If you have a case where it doesn’t work, you’re getting a little concerned. I completely agree that you need to balance the risk, and rejection is definitely something that’s on the table.

Amit Singal, MD: We have safety data coming out of Sinai. But to your point, there’s a publication bias. You know what I mean? If somebody has good outcomes, they’re like, “I’m going to publish this.” In cases where somebody doesn’t do so well, “I’m going to sweep that 1 under the rug.” There’s a publication bias, but this is something we have to figure out. What is the I/O? The immunosuppressive regimen. You put somebody on it after to prevent the rejection, [and there are] many questions that we don’t have the answers to.

Transcript edited for clarity.

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