Assessing Response to Sorafenib in Liver Cancers

Transcript:Ghassan K. Abou-Alfa, MD: I’ve got to go back to the same challenge that we actually faced in regard to the local therapy. Now, we have a patient started on sorafenib. Dose probably was ongoing at 400 mg twice daily, doing very well—maybe at some point some grade 1 hand-foot syndrome developed. Hold the drug for a week, restart it at the same dose, and then maybe later on, maybe 400 mg daily simply because of further grade 2 hand-foot syndrome. But the patient is doing well, CAT scans are repeating themselves. And, then, we look at the scan, and you’re going to see a little bit of more of that stable disease or maybe a little bit of growth, and the patient is not necessarily happy. They like to see tumor shrinkage. So, I’m going to go back to Riccardo, and from your perspective, as an interventional radiologist and as a radiologist, how do you assess sorafenib response? You have experience with this study and many others. How do we assess that? How can I assure the patient we are doing okay?

Riccardo Lencioni, MD: Well, I think the first thing is that you really need the expert radiologist in assessing those scans because interpreting HCC in cirrhosis in patients receiving different forms of therapy is not like the kind of bread and butter for any general radiologist. So, the first thing is to make sure that even the diagnostic radiologist is in the loop of the liver tumor board, and is engaged in this. Having said that, we do not really aim with sorafenib for any shrinkage of the tumor or any response in the classic term. There are responses, there are objective responses that have been measured. Some series have reported up to 10%, 20% of responders, but that’s not really the goal of the therapy. I would say that the lack of progression is what you typically consider as a sign that the treatment is efficacious. Although, there are studies that suggest that even in front of progression, no two progressions are the same, and the patient may still have some benefit from sorafenib even beyond progression. Actually, in some of the studies like the SHARP trial, treatment was continued beyond radiological progression. So, it’s an open question. I think as radiologists we can provide a fair assessment of response, recognizing the limitation of imaging in this area. I would say that probably this will be truly an area for more and more investigation. We still use alpha-fetoprotein. I was expecting the hepatologist to be more supportive of the alfa-fetoprotein, but this was a start.

Ghassan K. Abou-Alfa, MD: Well, in all fairness, it was for screening purposes.

Riccardo Lencioni, MD: Yes, for screening. You really have a cutoff or a percentage decrease that you would consider as the target. But, again, as the comprehensive assessment of the patient—in that context—having, let’s say, information from radiological imaging and alpha-fetoprotein combined can tell you how the patient is doing. Of course, as we discussed before, given that sorafenib is the only approved treatment for HCC at this point of time, this question is applying less pressure on the clinician than if it would be with more drugs available. I’m speaking about you guys.

Ghassan K. Abou-Alfa, MD: Well, if anything, please listen very carefully to what Dr. Lencioni said. This is very, very important! If you recall, when you go into the clinic and you look at the patient, you’re going to look them in the eyes, you’re going to examine them, and you’re going to be able to tell if they’re doing well or not. That’s a very critical component to see if patients are doing well on sorafenib or not. If anything, it was a component of the treatment on the SHARP trial, the CAT scan as well. Please look for yourself. This CAT scan can be very revealing and, if anything, talk to your radiologist, explain what form of therapy you’re applying here. This is an anti-angiogenic therapy. This class of drug has shown in multiple sites and multiple diseases that it can cause some form of “necrosis,” i.e., the tumor might still be there, it might even increase a little bit in size—as we heard from Riccardo—but still the treatment effect is over here. So, it’s very critical that you put all this collectively with the alpha-fetoprotein. It has never been validated, obviously, in regard to being a tumor marker but nonetheless in this specific patient, it might have value. Collect that information together to decide if this is the right treatment to go on the patient. With the lack of second-line therapies, except for clinical trials, sometimes we have to err on the cautious side, and accept that the patient might continue on therapy despite some progression, because clinically, they’re doing well until we have further confirmation.

With this said, I would like to move on to a very important part of the discussion—which is really what we’ll cover in the next 15 minutes or so—which is really where is the future going.

Transcript Edited for Clarity