Optimizing Treatment Selection in Liver Cancer - Episode 9
Transcript:Ghassan K. Abou-Alfa, MD: This brings me to another point, Katie, if you don’t mind telling us, because regorafenib already is used in colorectal cancer and you practice in that arena, as well, as a GI oncologist. What are the adverse events that we can expect there?
R. Kate Kelley, MD: I’d say in colorectal cancer, or also gastrointestinal stromal tumors, where we’ve used regorafenib extensively and it has a guideline indication, regorafenib has pretty similar toxicity to sorafenib and other multikinase inhibitors with antiangiogenic properties. We do see a sizable proportion of patients with palmar plantar erythrodysesthesia, or so-called hand-foot syndrome, that we see with this class of drugs; also hypertension, which is a clear toxicity that needs to be prospectively watched for. Making sure patients going on to regorafenib, or sorafenib for that matter, have well-controlled blood pressure, even before starting the agent, is critical. Loose stools and cumulative fatigue that builds up with TKI, or tyrosine kinase inhibitor, therapy are also seen. So, I’d say, in general, regorafenib is quite similar, in my experience. I have seen some patients in the colorectal cancer population with GI upset, but nothing I guess too untoward compared to sorafenib and other family members.
Ghassan K. Abou-Alfa, MD: Great. Riad, no doubt that the data are fascinating and we’re all happy to see it. It’s always good that we have new product and new drugs that are available for patients. The fact that now you have 2 drugs that improve survival to the extent that we’re describing, will this change your mind or views about when and how to move from local to systemic therapy?
Riad Salem, MD: Well, there’s no doubt that for patients, it’s a benefit. I think incorporating it in patient management can be complex and maybe this increases the complexity a little bit. The reality is when you look at BCLC staging and how patients flow, they really, to me, jump around from stage to stage if you really look at it clearly. They can go from A to C depending on performance status, etc, then back to B. I think it’s something that we recognize. It’s something that we need to learn to manage, but the reality is these are things we need to know about. I’ve always been an advocate of adjuvant sorafenib, but I don’t know what to make yet of regorafenib in that setting. Is it equivalent? Should we be thinking about it as well? And so this is, to me, the fun part of HCC. It’s always a learning opportunity, with very high-level clinical trials that are being performed—thousand-patient studies, randomized, overall survival—and published, for example, in Lancet and the New England Journal of Medicine; fantastic stuff that’s being done. It’s always a learning opportunity. For me, personally, I have to see where the regorafenib is going to fit in, and we’ll see. I don’t know that it’s always going to be cookie-cutter sorafenib, where you progress on locoregional therapy, then you progress and get sorafenib, and then progress and get regorafenib. Ideally, that might be the case, but again, I think as Richard was alluding to earlier, the multidisciplinary nature of how HCC is managed is something of interest.
I did want to highlight something that was mentioned earlier, which is the multidisciplinary aspect of managing HCC. One of the fun parts is not just the initial discussion, but one on the management. And so, we also—and I think all you guys do as well—look at follow-up images in patients managed in our HCC clinic. It’s a fun interaction because the imaging can be off; as Katie was mentioning, the flow dynamics, the mRECIST. An ablation lesion looks different than something managed with sorafenib, or Y-90, or DEB-TACE. And so, I think one thing to highlight for the viewers is that also interpreting the follow-up, as a group, is a good educational experience for all of us because we learn how to manage these things and we learn things that we never expected, like the pattern of progression matters. Is it a lung metastasis? Is it an adrenal metastasis? Is it PVT? Is it ECOG? So, these are all things that we learn because of the level of interest and the excitement in HCC.
Ghassan K. Abou-Alfa, MD: That’s fascinating. Actually, just to describe that in other words: what we thought simply might be first-line therapy, like sorafenib, followed by second-line, likely regorafenib, actually we’re adding another level of complexity here that Dr. Salem was alluding and eloquently saying. Not only are we looking in the vertical sense, but we’re looking now in the horizontal sense, which—especially with that interaction between the BCLC-B and BCLC-C, with the regorafenib data, and the add-on of the regorafenib after sorafenib—is going to be something that will be definitely looked into and tested quite extensively. With this said, Richard, back to you. On the study, again, there was one argument that these patients tolerated sorafenib very well, they’re really prepped for the regorafenib. So, please comment a little bit about the adverse events noted on the study itself and, at the same time, what’s your counterargument to this point?
Richard S. Finn, MD: Well, I think to pick on RESORCE versus any other study is a little unfair, and maybe you’re good at making an argument. Every clinical study is done with a select population of patients. That’s how we establish proof. That’s how we generate evidence. And then, there’s the practice of medicine where you incorporate that data. Important in the study design is patients were required to tolerate sorafenib and progress on sorafenib, with very strict criteria of what that meant. Patients had to be on sorafenib for 20 out of the last 28 days and have documented progression. You alluded to the fact that after they had progressed, they had to enroll in a study in a certain period of time. And at the end of the day, in reality, about half of the patients on the study were tolerating 800 mg a day, or 400 mg twice a day. Whether any of us feel that represents our individual population, that is open to debate, but that is the group of patients who went on to the study. As Katie mentioned, the toxicity and the tolerability in colon cancer seem much different than the tolerability in the liver cancer field and the liver cancer study. And part of that is patients were required to tolerate sorafenib, which does have a similar toxicity profile. So, right there, maybe that’s why patients were on sorafenib for 7 months, then they went on to this drug and they’ve tolerated it pretty well. The discontinuation rate was not as high as seen in other diseases.
With that being said, the clinical activity of the compound was very similar to the frontline data: 3 months’ improvement in overall survival. I think it’s important for us to recognize what the phase III data represent and then incorporate that into our practice. Does that mean for a patient to go on your study, they are going to be on sorafenib for 7 months? No. I would say that for patients who are on sorafenib and have radiographic progression, then those are patients who would be candidates for regorafenib. I think an important thing to take away, and it goes a little bit to what Riad was saying, is it relates to the fact that patients have a window of opportunity to be treated with systemic therapy, and that means frontline. That means recognizing when, if a patient was on locoregional therapy, they are progressing, so they get an opportunity to get frontline therapy. But the only way they’ll get second-line therapy is if they get frontline therapy, recognizing when frontline therapy has maximized its activity. Ultimately, patients get a chance to get this continuum of sorafenib to regorafenib.
Transcript Edited for Clarity