Richard Finn, MD: The patient continues on treatment for several months. She has a relatively stable disease. Her symptoms are controlled on sorafenib 400 mg/daily and on a monthly visit. She comes in about 10 months later, and she has evidence of some liver decompensation. At this time, she has developed some ascites, her bilirubin has risen to 2 mg/dL, and her albumen has fallen a little bit. The question becomes, how do we manage her?
So, this is someone who, on imaging, has had relatively stable disease, but now has progression and some decline in liver function, which is not uncommonwhether or not this is the natural history of her liver disease. Even sometimes subtle changes in her tumor that we can’t really pick up on a scan can cause stress on her liver and further decompensation.
We have a few choices at this point. One is to recognize that she has an incurable malignancy, and sorafenib has been shown to extend survival and help control tumor growth. But this patient, based on her clinical course, likely will succumb to her liver dysfunction at some point, whether or not we continue sorafenib, stop it, or change to another agent are our courses of action.
Depending on her sense of well-being, I think it’s very reasonable to just continue sorafenib in this case. Sorafenib has never been shown to improve survival in patients who present with Child-Pugh B, but this patient’s a little different in that she had been on sorafenib for some period of time and has now decompensated a little bit. But if her performance status is preserved, she can come to clinic. She’s not having significant side effects. Otherwise, I think this is a patient we could continue on treatment in hopes that we’re still getting a benefit by slowing down radiographic progression, even though she had some clinical progression.
The other option would be to stop treatment altogether. I think that would be a very appropriate thing to do if she had a decline in her performance status, she is not feeling well, or she has other stigmata of end-stage liver disease, such as continued weight loss or muscle wasting, with the idea that continuing sorafenib in that setting may not be of any benefit.
At this point, we have no drug that has been approved in the second-line setting. We know data from the RESORCE studythe study that evaluated regorafenib in the second-line setting in advance liver cancer—was positive. In that study, we used patients who had progressed on sorafenib radiographically but were still Child-Pugh A and had good performance status, and those patients were randomized to regorafenib or placebo. That has been shown to improve survival.
At this point, she doesn’t really qualify for that type of treatmentone that’s not FDA approved as of yet. But she would not qualify for that proven survival advantage anyway, because we don’t know the role of that drug in a patient who is Child-Pugh B.
I think, at the end of the day, our choices would be to continue sorafenib or not. This patient decides to continue on sorafenib in consultation with her physician, 400 mg/daily, and she would be followed until she has evidence of further clinical progression. As we start thinking about treatments for second-line liver cancer, it will be important to try to find patients who qualify for proven second-line treatment, and that will be patients who have radiographic progression but also have preserved liver function. We’ll have to maintain an active treatment role in our patients to help get them to an optimal treatment regimen.
Transcript edited for clarity.