Case 2: 67-Year-Old Woman With Refractory HCC



Farshid Dayyani, MD:Our second case is a 67-year-old woman who presented with a new onset of abdominal pain and was referred for further laboratory tests and imaging studies.AFPwas found to be elevated at 540 IU/mL. She had multiphasic contrast MRI [magnetic resonance imaging] of the abdomen, which unfortunately showed the 8-cm encapsulated mass in the left hepatic lobe showing hypervascularity on the arterial phase and washout in the venous phase. She had more staging studies with chest, abdomen, and pelvis imaging, which showed no metastatic disease. Based on the imaging, she was diagnosed with unresectable hepatocellular carcinoma [HCC].

In terms of her underlying liver function, given the portal hypertension, platelet count was 75,000 mm3. She was categorized as Child-Pugh A6 score for chronic liver disease, based on a bilirubin of 1.8 mg/dL; albumin a little bit low, at 2.9 g/dL; and INR [international normalized ratio] of 1.5. The platelet count we talked about was 75,000 mm3. She had no encephalopathy or ascites at the presentation.

With unresectable disease, she underwent trans-arterial chemoembolization [TACE] X2, and follow-up imaging at 1 month unfortunately showed progressive disease with a risingAFPof 720 IU/mL. Based on that and based on the data we discussed from the REFLECT trial, she was started on lenvatinib, 12 mg once daily, with stable disease at 3 months. Ultimately at 9 months the MRI showed now progression in the liver, a new adrenal lesion, extrahepatic disease, andAFPthat went back up to 650 IU/mL.

Ghassan Abou-Alfa, MD, MBA:Thanks so much, Farshid. If anything, this case is quite fascinating, especially because from the beginning—and I think you mentioned this, if I understood from you—the tumor was deemed unresectable because of vascular involvement. Ultimately the dissection of the data reflected Child-Pugh A, despite being on the edge with albumin, was not our favorite. Bilirubin was a little high, and a lot of it got embolized. Riad, for you, after embolization that many times, what do you think?

Riad Salem, MD:Well, a couple of things. I just wanted to highlight again, these are solitary lesions, large, and technically BCLCA [Barcelona Clinic Liver Cancer stage A], right? All solitary tumors are BCLCA, and this is another example of the state of migration concept when you can’t fit the recommendation at that time and then you migrate to the next treatment. In this case, locoregional therapy; in this case, chemoembolization.

There’s always a lot of talk about, how many times can you chemoembolize someone? And the narrative of 2 chemoembolizations is really something that has stood the test of time. I actually think that’s reasonable. I think there are some data out there that show that you sometimes need the second locoregional therapy, the second chemoembolization, to augment the first response. You don’t declare failure until you do it twice.

As I mentioned before in the other case, you have to be careful how many times you do that because different patients will tolerate the number of chemoembolizations differently. This is a multidisciplinary team, so we review the follow-ups in tumor board. There’s no such thing as the patients just being seen in IR [interventional radiology] and disappearing for 3 months, disappearing from hepatology, disappearing from oncology. Everybody is reviewed, and we make sure we follow their liver function tests. In this case, I think there were 2 chemoembolizations. The left side is very reasonable, and there was some response here. I assume this was after the second chemoembolization. And I think that was following protocol.

Ghassan Abou-Alfa, MD, MBA:Fair enough. Amit, this setup of the Child-Pugh A was not like, “Wow.” It was, “OK, but on the edge,” and with the platelet count of 75,000 mm3, do you think that it was pushed a little more than needed in regard to local therapy?

Amit Singal, MD:Yes, I think you’re right. This patient once again technically is Child-Pugh A. So they get an extra point for their albumin. As you said, the bilirubin is 1.8 mg/dL. It goes up just slightly, and they get an extra point for that. Albumin is close to the edge. If it goes down a little, they get an extra point, and then they’re a solid Child-Pugh B. And you’re looking at a completely different story. I think this goes back to Riad’s point. It’s not as if you hand off the patient and you do multiple chemoembolizations without reassessment. I think you would do the first chemoembolization. You’d probably get imaging as well as a reassessment of liver function. And if you find that the liver function is starting to decline, that’s another avenue of TACE failure, you may then consider a transition to systemic therapy. I think close monitoring of response as well as liver function as you go through this process is critical.

Of course, what we have here is that we say that the patient underwent 2 chemoembolizations without a lot of detail about what happened between those 2 chemoembolizations. I assume this patient was being followed in a multidisciplinary setting, and I assume the patient’s liver function was stable. I think the devil is always in the details, and these patients are always different. It’s a matter of how selective you can be. It’s the type of thing where if you treat selectively with the chemoembolization, you’re able to treat the HCC and have very few off-target affects, and the liver functions naturally remain stable despite being on the edge.

Ghassan Abou-Alfa, MD, MBA:Would you have thought differently, Farshid? It’s your case, but would you have loved to start the systemic therapy anytime earlier?

Farshid Dayyani, MD:I think we would need a little more information. I agree with Amit on this. Maybe I think in the future, it would be more likely when we have more of the robust data showing that treating the patients earlier will improve outcomes with more output in systemic treatments. I think the answer will be in the future. It’s probably much more likely than today on this case.

Ghassan Abou-Alfa, MD, MBA:Yes, if anything, interestingly, for us in the United States we don’t have such data, but no doubt our colleagues in Japan have delineated for themselves a certain regimen. How many embolizations? What’s the sequence? What’s the time between embolization to be sure people are not pushed to the edge before they get into systemic therapy? Anyway, in that case here, the patient ultimately, as you mentioned, got on systemic therapy, got lenvatinib—and we spoke plenty about lenvatinib. We like very much, as we said, the noninferiority for sorafenib. We definitely are happy to see that the progression-free survival is almost 3 times higher than for sorafenib. We like the response rate of 26% very much by RECIST 1.1 and 41% by modified RECIST.

But at the end of the day, despite all this good material—and this is an amazing drug, and people can stay quite well on it for a long time—then people are going to progress. The same as your patient over here.

Transcript edited for clarity.

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