Hepatocellular Carcinoma - Episode 3

Case 1: Treatment Considerations for Recurrent mHCC

December 2, 2019


Ghassan Abou-Alfa, MD, MBA:As we heard, Farshid, ultimately and sadly, the patient recurs. The reality is that a lot of patients unfortunately recur. This is the nature of the disease, as Riad just mentioned. So now we have metastatic disease. What are you going to treat them with?

Farshid Dayyani, MD:As you know, for decades we had only 1 option in this schedule with sorafenib based on 2 randomized phase III trials, and it was really a graveyard for our medical oncology with 14 negative trials in first line and second line. More recently, lenvatinib for the first time was shown to be noninferior to sorafenib in a randomized clinical trial in the first-line setting based on the REFLECT trial, which was about a 1000-patient study randomized in first line to lenvatinib dosing based on weight, 8 mg or 12 mg, versus sorafenib. It’s primary end point was overall survival noninferiority.

But I think more importantly, there were secondary end points, such as a tumor response, progression-free survival, and time to progression. The trial met the primary end point. It was noninferior in terms of overall survival at 13.6 months for lenvatinib versus 12.3 months for sorafenib. But if you look at the pharmacodynamic outcomes, meaning progression-free survival and response rate, you see very significant improvements with lenvatinib. The cohort, their progression-free survival was almost doubled, 7.4 months versus 3.7 months in the sorafenib cohort with a ratio of 0.66. And importantly there was a 24% objective response rate based on resistance criteria of 1.1 versus 9% of the sorafenib cohort. And that translated into a longer time to progression, almost 9 months with lenvatinib versus sorafenib, which was around 3.7 months. Clearly the patient will be able to stay longer on treatment, first-line treatment, and get a meaningful benefit from first-line treatment if you look at the secondary end points for this patient.

Ghassan Abou-Alfa, MD, MBA:I can’t thank you enough. I’m really impressed that you know all those data, which are, by the way, fascinating data. If anything, I have to say, you clearly like lenvatinib. I can see that. And you know what, I’m not questioning you on that, because I like lenvatinib too. It’s a great drug. It’s an excellent drug. Let’s dissect 2 things, however. We go to lenvatinib, and we’ll go back to your data, but let’s go back to Amit for a second. We spoke a little in the beginning when you presented the case about the liver functionality and Child-Pugh. Let’s talk a little about what Child-Pugh is.

Amit Singal, MD:Child-Pugh is a way that we can assess liver function. It’s based on 3 variables, and it’s based on the presence of 2 things that are hepatically compensation. You can have hepatic encephalopathy, and you have ascites. The 3 lab variables are bilirubin, albumin, and INR [international normalized ratio]. Essentially, depending how normal or abnormal those are, you get anywhere from 1 to 3 points. You add them all up, and so that score goes 5 to 15.

But this is a simple way that we can all objectively speak about liver function and communicate with one another. And it’s like grade school: A is the best, and C is the worst. When you take a look at all these trials, these trials included people with good liver function, Child-Pugh A. The tough thing about clinical practice is not everyone has Child-Pugh A disease. You then have to extrapolate these data to people with not as healthy livers, Child-Pugh B or Child-Pugh C patients.

Ghassan Abou-Alfa, MD, MBA:I like the way Amit is describing it. It’s really the 5 parameters. There’s more or less a certain sequence of how they occur; it’s not hazard. It’s not that somebody starts with ascites or encephalopathy. But usually the albumin, bilirubin start moving in the beginning. Then this will be followed by probably the ascites. Then again, the encephalopathy and the PTR [proton transfer reaction] will be lost. This is really how the sequence is.

Again, bilirubin and albumin, ascites, encephalopathy, PT [proton transfer], INR. More importantly, even though it looks like a grading of A, B, and C, they are not linear. It’s not that A occurs at the same rate of B and C. People live on a really long, long, horizontal line of Child-Pugh A, then there’s a little of the curve of B, and then there is shoot of C. That’s why it’s really important to us to really focus on and try to catch patients very early in the game.

And I’ll go back to Riad here. There is 1 thing I would like to hear your comments on, to see if you agree with me. What I’m really impressed with in the case that Amit presented is that a patient was caught early with regard to the recurrence. Also, he was acknowledged and caught early with regard to the need for systemic therapy. The patient is still Child-Pugh A. Your thoughts on that?

Riad Salem, MD:Look, there’s no doubt that I as an interventional radiologist and we in the interventional radiology community recognize that first and foremost, all the data generated for advanced systemic therapy for HCC [hepatocellular carcinoma] are based on Child-Pugh A disease. We know that we have to be on the lookout for that. All the therapies that we have applied, the outcomes are based on Child-Pugh A. So we are actively communicating with medical oncology, with hepatology, and with surgery to make sure that in a continuous process, we’re looking at liver functions and making sure that we don’t overtreat with any type of therapy. Locoregional therapy included, of course.

The communication with the team starts from day 1. It doesn’t start after we’ve done multiple locoregional therapies, it starts from day 1. We’re working together, and there are some people who decompensate after 1 locoregional therapy; there are some who can tolerate 5, 6, or 7 of them. It depends, but we are actively involved in that, and we know that. We want to make sure that patients are able to benefit from all the treatments, the locoregional therapies, and also the systemic therapies.

Ghassan Abou-Alfa, MD, MBA:I like that. This is very important. If anything, it really reemphasizes the need for the multidisciplinary team. As you see, we’re from different disciplines, and we still are discussing the case. Because really this is what we do today. It’s very important is that you don’t hog a patient because of his certain specialty. Patients need to be seen by the different specialists: the hepatologist, the oncologist, the surgeon, the interventional radiologist, and many others as deemed necessary. By all means.

Transcript edited for clarity.