Hepatocellular Carcinoma Update, Issue 1, 2017 (Video Program)Potential utility of immune checkpoint inhibitors in the management of HCC
6:57 minutes.
TRANSCRIPTION:
DR LOVE: What do we know about anti-PD-1 agents in HCC, particularly nivolumab? DR LLOVET: Here I’m showing the 2 studies, the first one with 42 patients. Of course, these are single-arm studies. Objective response 19% and 1-year survival 62%. But appealingly enough, they expand the cohort to 200 patients. It’s beyond that — 215, I think, that they reported at ASCO in 2016. And these include patients with hepatitis B virus, hepatitis C virus and other etiologies, because there was some concern that eventually, due to the neoepitopes and everything, hepatitis B and C virus infection may have a different response. But they certainly identified that there were no differences between the subgroups depending on etiology. These 2 figures are interesting because 16% objective response according to RECIST — it’s appealing, and 14 months of median survival. Most, up to 60%, of these patients were second line, so were patients that progressed to sorafenib and then were receiving nivo — most of the patients in this trial. Fourteen months is really a signal of efficacy, considering that we have here around 200 cases. So all the regression to the mean has occurred, and if it’s a true fact, it’s certainly a very strong signal of efficacy. The trial now, head-to-head comparison, nivo versus sorafenib, is almost completing recruitment. They mention that eventually, in a couple of months, the recruitment will be completed. So we are very eager, also, to understand these data with nivo. Also, we are very interested — I’m not sure if, with the trial, we will have this information — to understand which group of patients will benefit from that, because, for instance, you are very familiar with studies from the group of UCLA in melanoma suggesting that the patients with PD-L1 immunostaining positive are the ones responding to nivo, or the studies with non-small cell lung cancer with pembro, also suggesting — not suggesting — that the indication is bounded by the companion diagnostics of having a positive immunostaining for PD-L1 to receive pembro. In HCC we have been studying that. And we know that there is 25% of the patients that belong to what we call the immune suppress. And they have all the characteristics that may suggest that these patients may respond to nivo at this point. So I think it’s very promising, nivo. But let’s see. DR LOVE: The issue that comes up in pretty much all cancers where you look at data like this is the issue of the prolonged response. And actually there was a paper by the lung people at Memorial talking about, “What should we really be looking for in these trials of checkpoint inhibitors?” Because, for example, you talk about 14 months, but that’s in all comers. DR LLOVET: Yes, that’s right. DR LOVE: And what people really want to know is, what is the chance that somebody’s going to go progression free — I don't know — for a year or two? DR LLOVET: Yes. DR LOVE: Usually when you start to see these data coming out, all I can do is ask the investigators, “Do you see prolonged responses?” Do you see them in HCC? DR LLOVET: Yes. They reported, I think, prolonged responses, particularly in the patients achieving objective response. If you are achieving objective response, then the likelihood that you have prolonged responses or even free of the disease at 3, 4, 5 years is very high. I think that the details have not been published yet, but they certainly provide information on prolonged responses in those achieving objective response, so it’s the same phenomenon that happens in the other cancers. DR LOVE: What about complete clinical responses? Have they been observed? DR LLOVET: I think that they have. Very few, but they have, also, complete responses. DR LOVE: What’s been seen in terms of toxicity with checkpoint inhibitors in patients with HCC? Obviously there’s experience with all different kinds of cancer, but particularly these patients with chronic liver disease. Any unusual tolerability issues? DR LLOVET: No. I think that it’s very well tolerated. The reports, particularly this report, show very well that the drug is very well tolerated. DR LOVE: What about combination with checkpoint inhibitors? Of course, one that’s actually part of melanoma treatment at this point but being looked at in a lot of cancers is PD-1 with anti-CTLA-4. Has that been looked at with HCC? Is there any interest in that? DR LLOVET: Yes. The trial is ongoing in Phase II, the combination of ipilimumab and nivolumab in combination. This is one of the combinations that is out there. DR LLOVET: There are other combinations ongoing with nivo plus sorafenib that is the standard of care. And I heard, but I have not participated in, the studies that are trying to boost the expression of neoantigens, for instance, with MEK inhibitors and nivolumab. So these are the 3 initiatives that I am familiar with. Particularly, the combination with ipilimumab and nivo is ongoing, and sorafenib and nivo is ongoing. And the other one, I think that they want to arrange that. DR LOVE: It’s interesting, this idea of the MEK inhibitor with PD-1, because we did see some data in colon cancer — non-MSI-high, that they saw a few responses. So, that was interesting. Another thing that you hear about, again in different cancers, is the idea of the potential synergy with, say, radiation therapy. And I was curious about the idea of spheres plus PD-1 antibodies. DR LLOVET: The spheres, you mean chemoradiation with yttrium-90? DR LOVE: Yes. DR LLOVET: That could be something that may be appealing, but I’m not aware that is ongoing in any trial in this direction at this point. |