Hepatocellular Carcinoma Update, Issue 1, 2017 (Video Program)Efficacy of anti-CTLA-4 antibodies alone and in combination with anti-PD-1 antibodies
2:56 minutes.
TRANSCRIPTION:
DR LOVE: What do we know in general about anti-CTLA-4 agents in HCC and also the combination of PD-1 and anti-CTLA-4? DR EL-KHOUEIRY: Tremelimumab actually was the first checkpoint inhibitor to be evaluated in HCC as a single agent. There’s a study from Bruno Sangro from Spain that was published in the Journal of Hepatology, a small study, Phase II study with tremelimumab as a single agent, where he had a response rate of about 18%. He included patients with both Child-Pugh A and B, certainly an advanced population, and had an overall survival of 8 months. But at least they showed the feasibility of evaluating a checkpoint inhibitor in that setting. They had more AST and ALT elevations with tremelimumab at the dose used in that study and in those patients. So I’m not aware of tremelimumab being evaluated currently as a single agent anymore, but certainly in combination with durvalumab, that’s ongoing. As part of the CheckMate 040 trial, which is the Phase I/II of nivolumab that we’ve been talking about, there’s now been a cohort of the combination of nivolumab and ipilimumab. That’s completed accrual, as well. And we evaluated different doses of ipilimumab. We’re still waiting for the safety readout, as well as the efficacy readout on that part, as well. DR LOVE: And of course that’s a big question in a number of other cancers. Any guesses about what we’re going to see, other than more toxicity? DR EL-KHOUEIRY: I think the toxicity will be dose dependent, from what we’re learning in other tumor types and from my anecdotal experience so far. It’ll depend on the ipilimumab dose that’s used. The challenge, though, is that the increased efficacy may be linked to the dose of ipilimumab. That’s if you’re asking me to guess. So we will see. DR LOVE: Speaking of toxicity, you do see LFT elevations/hepatic toxicity with checkpoint inhibitors. Do you see this with HCC? And how much of a problem is it? DR EL-KHOUEIRY: That’s a great question again. The Grade 3 and 4 AST/LFT elevations with nivolumab were actually in the range of 3% to 4%. If you look at all-grade elevations, most of the AST/LFT elevations were transient and were self-limited. In the dose escalation part of the study, many of the patients who had elevations even without initiation of steroid therapy, many of them, actually, their liver enzymes came back down on their own. And the liver enzyme elevations were not accompanied by signs of liver decompensation. They were not in conjunction with bilirubin elevation, of new-onset ascites. So as far as liver toxicity, it is no different than seen in other tumor types. |