Hepatocellular Carcinoma Update, Issue 1, 2017 (Video Program)Durable objective responses to nivolumab in advanced HCC
4:07 minutes.
TRANSCRIPTION:
DR LOVE: What about the issue — and this comes up in many other cancers — of duration of treatment, patients having prolonged progression-free survivals? There’s been a lot of discussion about whether, even, we’re looking at the right endpoints. But I don't know, maybe you could pick 2 years, for example. I don’t even know if there’s enough experience at this point. But do you have any feel for what fraction of patients have survival that’s just completely beyond what you would expect? And is this mainly responders? DR EL-KHOUEIRY: Well, these are great questions. Some things to help, maybe, clarify and address your question: The median duration of response in the dose-escalation phase, where we have longer follow-up, was 17 months, so these are very deep, durable responses. Among the responders actually were 3 complete responses in the dose-escalation phase. In the patients who have stable disease we see a range of stability lasting as long as 17, 18 months. So I think that the benefit seems to be from both the responders as well as the patients who have stable disease that is quite durable. As far as percentage of patients who are alive or the survival rate at certain specific time lines, let’s say at 9 months, et cetera, for the overall population — again, the 200 and some patients — the 9-month survival rate was actually around 70%, which is, again, comparing to other historical data, quite promising. Again, one of the tricks with immunotherapy, to mention here, like all immunotherapy studies, we allow for this phenomenon that’s referred to as pseudoprogression. We don’t abandon the therapy at the first sign of progression. So if a patient’s doing well clinically, there is some radiologic progression, we definitely kept these patients on therapy. Many of them actually subsequently stabilized. And a minority had some degree of response, subsequently, as well. DR LOVE: That’s certainly a theme we hear throughout oncology. What do we know about PD-1 levels, first of all in HCC in general, but also in relationship to treatment benefit with HCC? DR EL-KHOUEIRY: Previous reports, which, again, were small reports, reported a broad range of PD-1 and PD-L1 expression — anywhere from 20% to 60%. In our clinical trial this data is still coming together. But the PD-1 positivity rate on tumor cells — just to be specific, because you can look at PD-1 and PD-L1 on different cellular subtypes. I’m talking about PD-1 expression on the tumor cells themselves — was actually in the range of 20%. And the responses occurred independent of PD-L1 expression. We saw objective responses in the PD-L1-negative as well as the PD-L1-positive patients. So in the limited experience so far, looking at PD-L1 expression on tumor cells, it does not seem to be a predictive marker at this point. DR LOVE: What data do we have on other checkpoint inhibitors beyond nivolumab in HCC? DR EL-KHOUEIRY: There have been small reports with pembrolizumab, another PD-1 inhibitor/PD-1 antibody; with durvalumab, which targets PD-L1. There is a second-line randomized Phase III study of pembrolizumab versus best supportive care that is ongoing and accruing. And there’s an ongoing, I believe, Phase I or Phase I/II study with durvalumab in combination with tremelimumab, so a combination of PD-L1 and CTLA-4 inhibition. These are ongoing at this point. |