Hepatocellular Carcinoma Update, Issue 1, 2017 (Video Program)Clinical experience with and side-effect profiles of regorafenib and sorafenib
5:51 minutes.
TRANSCRIPTION:
DR LOVE: Getting back to regorafenib, have you adapted that to your practice? Are you using it second line? DR EL-KHOUEIRY: We have certainly used it in select patients in second line. And we’ve tried to follow the eligibility in the study since we’re still learning to use it in patients with HCC. These are patients who had progressed on sorafenib — who had tolerated sorafenib reasonably well and had definitive radiologic progression. And, yes, we’ve tried it. And I would say our experience, although small at this point, has mirrored what was reported in the publication, that about 50% of patients were able to tolerate the full dose. Another 50% required interruptions or reductions. DR LOVE: Globally, when you think back on your clinical experience with sorafenib, in general, what fraction of patients do you think actually benefit from the drug, that you can, afterwards go, “I think that patient benefited”? DR EL-KHOUEIRY: Well, I would say again, with sorafenib the challenge is, we don’t see tumor reduction radiologically, and we’re relying on the stabilization of disease. But I can tell you, certainly, that in the 30% to 40% of patients who actually present with symptomatic disease — let’s say, pain, fatigue, et cetera — I certainly see about 30% to 40% who tell us that they’ve had an improvement in symptoms. That’s a good, practical measure of benefit. If you look at the publications, I mean the disease stabilization rate is as high as 60% to 70% with sorafenib. And we certainly do see that. And one of the keys with these TKIs, such as sorafenib, is to also not quit too early. I mean, these are patients that you put on treatment. Their first scan may show minor changes, minor increase in some tumors, but what’s not reported frequently on radiology reports is the fact that the tumor potentially could be becoming less enhancing, less active. There’s some necrosis. So if we’re looking superficially at radiology reports and only looking at size, we may be fooled and quit early. The other thing that could happen in the liver, you could have appearance of small, nonspecific arterially enhancing lesions, a centimeter here or there. And these may not be very meaningful. So one of the keys to seeing the benefit of sorafenib is to maintain the therapy until there is definitive radiologic and/or clinical progression. DR LOVE: Globally, what fraction of patients do you think benefit from second-line regorafenib? DR EL-KHOUEIRY: The regorafenib benefit, again, is slightly narrower because by selection criteria for the clinical trial the patients had to have tolerated sorafenib. They had to have had definitive radiologic progression. If you look at the publication, the median time on sorafenib for these patients was 7 to 8 months. So these were patients who actually had done well on sorafenib and had tolerated it. And they’re the ones who went onto the study. So I think the population that benefits from regorafenib, based on that reported trial, is narrower. And I think right now I encourage my colleagues to stick to the eligibility that was reported in the trial because that’s where we’re more likely to see the benefit, before we start expanding the usage. DR LOVE: It’s been interesting to trace what’s happened in terms of dosing of regorafenib in colorectal cancer. We’ve worked with your colleague Heinz Lenz a lot, and they often — of course, those patients haven’t had a prior TKI. And a lot of people reduce the dose preemptively to 120, even to 80. Again, on these patients who have tolerated sorafenib, globally, it sounds like a number of these patients actually can tolerate full dose. When you do see toxicity, what do you see? DR EL-KHOUEIRY: If we talk about the higher-grade toxicities, Grade 3 and 4, the most common ones were expected: hypertension, diarrhea, fatigue. I would say these were the top 3, probably. Interestingly enough, as far as high grade, there was no difference in hepatobiliary events: elevation of liver enzymes, bilirubin, ascites. It was actually quite similar — if anything, slightly more frequent overall in the placebo group than in the regorafenib group. The skin toxicity was actually not very high and was quite minimal and low grade. So it is interesting that, if I do a cross-trial comparison between colon and HCC, the tolerability is different. And some hypotheses have to do with the fact that colon cancer patients have received multiple cytotoxic regimens before they get to regorafenib, versus the HCC patients who are getting this as second line. And they’ve already proven that they can tolerate the sister drug, sorafenib. So that could be the difference. DR LOVE: That’s very interesting. What about trials looking at regorafenib first line against sorafenib? DR EL-KHOUEIRY: I’m not aware of any trials comparing regorafenib to sorafenib head to head in first line. And at this point we actually do not have first-line regorafenib data. I think there are potential trials in discussion combining regorafenib with other compounds, including immunotherapy, potentially. Those I’m aware of. |