DR LOVE: Let’s talk about checkpoint inhibitors and the data that’s come out looking at them. You’ve been very involved with that. Can you kind of go through that?

DR EL-KHOUEIRY: Sure. The trial that I’ve been involved in is the Phase I/II study evaluating nivolumab, the anti-PD-1 monoclonal antibody, in patients with advanced HCC. This was a Phase I trial initially, so there was a dose escalation. And the dose escalation was carefully done in parallel groups. So there was a group of patients, in fact, with hepatitis B, a group with hepatitis C and a group of uninfected patients. And the reason is because we had no safety data for treating patients who have a viral infection with these checkpoint inhibitors.

The summary here is that the tolerability profile during the dose escalation of nivolumab was similar to that of nivolumab in other tumor types. Escalation up to the standard dose of 3 mg/kg, there were actually no dose-limiting toxicities in any of the groups. The only dose-limiting toxicity was in a patient who was uninfected, at the 10 mg/kg dose, who had liver decompensation and soon after was found to have, actually, progressive disease. So from a safety perspective, the dose escalation showed good tolerability.

The Phase I was followed by 4 parallel expansions of 50 patients each: 50 patients who were uninfected and sorafenib naïve, 50 patients who are uninfected and sorafenib progressors, 50 patients with hepatitis C and 50 patients with hepatitis B. So the total population now, if you look at both the escalation and expansion, is around 250 patients, which is a great, large experience.

And we’re seeing an overall response rate, objective response rate, using RECIST 1.1, of 20%. And the responses seem to happen across all etiologies, whether it’s hepatitis B, C or uninfected. They also seem to happen independent of whether the patients had prior sorafenib or not. That’s important to notice as well.

The follow-up is not mature for all the patient categories. From the dose-escalation part of the study, which is about midforties, 45 patients or so, 48 patients, the median survival for the patients who were sorafenib exposed already was about 15 months. The median survival for the patients who are sorafenib naïve was about 14 months. Overall, the median overall survival for patients who were sorafenib exposed, for the overall population, was about 13 months. We’re waiting for the survival data to mature for the different subgroups at this point. But in short, there is an important signal as far as response rate. And there is a promising signal as far as overall survival.

Efficacy of sorafenib and integration of the recently FDA-approved multikinase inhibitor regorafenib into the treatment algorithm for advanced hepatocellular carcinoma (HCC)

Immune checkpoint inhibitors in the management of HCC: Biologic rationale and emerging data

Activity and tolerability of lenvatinib for patients with unresectable HCC

Management of local-regional disease