Hepatocellular Carcinoma Update, Issue 1, 2017 (Video Program)Potential role of immune checkpoint inhibitors in the clinical management of HCC
4:49 minutes.
TRANSCRIPTION:
DR LOVE: So based on the available clinical data right now, putting aside FDA, cost/reimbursement — based on these data, how do you think checkpoint inhibitors — and it seems like nivolumab, there’s a lot more experience with — should be integrated into nonprotocol management? DR EL-KHOUEIRY: Well, I think what we know about nivolumab specifically — and in checkpoints, they — again, the striking tolerability in HCC is important. This is a tough disease, as we all know. There’s concurrent cirrhosis, liver dysfunction, et cetera, so the safety profile is certainly favorable. And again, the early signals of efficacy are promising. As far as off-label usage, it may be used — the majority of the data right now is in patients who are post-sorafenib, I would say, from the initial Phase I/II study. But there’s certainly a group of patients who were sorafenib naïve, as well. So, it’d be hard for me to extrapolate from that and make practice recommendations, but the data is there. It’s promising. The randomized Phase III study of nivolumab versus sorafenib also should be reading out in the coming year or year and a half, probably. So we will have more data coming. DR LOVE: But for practical purposes, in your own clinical practice, if you have a patient who’s not eligible for a trial, do you attempt to integrate any of the checkpoint inhibitors into their management? And have you been able to even get it paid for? DR EL-KHOUEIRY: Sure. Yes, I have, occasionally. It’s been mostly in the second- or sometimes third-line setting where we’ve done that. As far as the ability to get reimbursement, it’s been, I would say, 50%. There are many patient-assistance programs with many of the pharmaceutical industry sponsors who have these compounds, as well. So I think the ability to access these agents for patients actually is there. It’s available. DR LOVE: Yes. I mean just based on the data that you described and looking at sorafenib, which is certainly very, very suboptimal therapy, to me, it seems like — I think if I were in that situation, I might want to get it first line. DR EL-KHOUEIRY: And that’s happening, of course, both on trial and off trial. It is happening. I’m aware of that happening. The challenge we have is how do you select patients? And we, right now, do not have the tools, right? Is this a patient who would benefit from sorafenib, or is this the patient that’s going to have a deep response with nivolumab in first-line therapy? And right now, it’s a guess. DR LOVE: We hear a lot of excitement from the renal investigators about combining VEGF TKIs with checkpoint inhibitors. Bob Motzer, he’s very, very excited about that. What about that strategy in HCC? DR EL-KHOUEIRY: It’s starting. It’s emerging. There are many clinical trials in planning phases combining PD-1 checkpoint inhibitors with different TKIs. I mean some with sorafenib/regorafenib, but some with other TKIs, including some of the other TKIs that have been evaluated in HCC: lenvatinib, cabozantinib, et cetera. These are in the planning phases at this point. DR LOVE: I also wonder about — you hear about that abscopal effect of radiation therapy with checkpoint inhibitors. I mean, at least theoretically, you hear that discussed. And in HCC, you do — there’s a lot of liver-directed, what I would call radiation-type treatment, particularly with spheres. Again, any interest in that strategy? DR EL-KHOUEIRY: Absolutely. Some of these trials have started. At the NCI, the group by Tim Greten is evaluating tremelimumab — an anti-CTLA-4 antibody — with TACE or radiofrequency ablation. And we’ve had some early reports from that study showing the feasibility of this approach and some proof-of-concept findings as far as recruitment of immune cells to the tumor, et cetera. So it’s certainly a potentially promising approach. There’s certainly strong rationale that the local-regional therapy might increase neoantigen exposure, et cetera. And I’m aware of other trials that are in planning stages, as well. |