Hepatocellular Carcinoma Update, Issue 1, 2017 (Video Program)Viewpoint on the potential integration of nivolumab into the treatment algorithm for HCC
5:45 minutes.
TRANSCRIPTION:
DR LOVE: Have you yourself treated any patients on trial or off trial with PD-1 inhibitors for HCC? DR LLOVET: Well, we have the trial ongoing in Sinai at this point with nivolumab versus sorafenib, yes. DR LOVE: And have you seen any clinically useful responses? DR LLOVET: Yes. Exactly. We have seen in a couple of patients. DR LOVE: Enough — and, again, this comes up all the time — enough that you’d be tempted to use it outside a trial setting? For example, if you could get it paid for? DR LLOVET: Yes. This is happening in the US, as you are familiar with. Nivo is approved by several indications at this point in the US. And the off-label use of nivo is happening in HCC as well. DR LOVE: Do you think that that’s a reasonable thing to do? DR LLOVET: Well, I personally prefer to treat the patients either according to the data we have — so in second line in patients progressing to sorafenib, I will start rego when this is possible. But if there is not a trial available, it’s something to consider. DR LOVE: Anything else you want to say about checkpoint inhibitors in HCC? DR LLOVET: No — I mean, as I mentioned, there is another trial in the second line in patients progressing to sorafenib with pembro versus placebo. This trial is up and running. And my impression is that — this is an impression, an opinion, so you can do whatever you want with this — I am not sure if the effect that we’re producing that is a certain clear-cut effect and long-standing effect in a subgroup of patients will suffice to track all the effect in terms of trial — the hazard ratio to a positive trial. I’m not sure about that. But I am positive that nivo is effective in a subgroup of patients. That’s in my mind, it’s very clear. And if the trial is positive, it is okay. If the trial is negative, I think that we have to identify the subgroup of patients because these drugs are certainly effective for a subgroup of patients. So we’ll have to jump to biomarkers here. DR LOVE: Do you think that we’re going to be using checkpoint inhibitors, specifically nivolumab, as first-line therapy in the near future? DR LLOVET: If the trial is positive, yes. DR LOVE: Any guesses about whether the trial will be positive or not? DR LLOVET: Well, according to the data. We were approached in 2004 because they had data on Phase II with 120 patients, with an objective response that was marginal, I have to say, but overall survival of 11 months. And we thought, Wow! Eleven months in a cohort of 120 patients compared to the natural history that is around 6, 7 months is clearly a signal of efficacy. So we recommended the move forward with a Phase III that was successful. Now you have this data, 200 patients, 14-month median survival. So we are in a situation in which this is a signal. We know that throughout trials, sorafenib can provide 11-month median survival. So there is a signal here that suggests that nivo may be potent enough. Let’s see what happened. DR LOVE: When you look at a trial — and also clinical practice — of people receiving sorafenib first line, what fraction of patients have not progressed a year later? DR LLOVET: Well, time to progression is around 5.5 to 6 months, so patients that do not progress in 1 year is less than 20%. DR LOVE: And I guess what I’m wondering about is, I’m assuming they’re going to look at something like that in the Phase III trial. Because it seems like the likelihood is you’d see more people without progression, let’s say at a year or year and a half, with a checkpoint inhibitor — although I don't know if that’s going to actually play out in the randomized trial, if you follow me. DR LLOVET: Yes. So I think that rather than checking tumors not progressing in 1 year, I think that the critical figure is, for instance, 3 years. DR LOVE: Three years. DR LLOVET: Yes, because then it’s really, really marginal, the cases that sorafenib is able to contain the disease at 3 years. But certainly with nivo, at least with other cancers, and I think in HCC it may happen the same, you may have a proportion of patients that have achieved objective response at baseline or after, after some cycles of treatment, that maintain the response throughout a long period of time. And this is where the benefit comes from. |