Nivolumab and Checkpoint Inhibitors in HCC



Ghassan K. Abou-Alfa, MD: So, let’s go back to the point that we just spoke about with Dr. Finn, which is in regard to nivolumab. It was based on phase I/II data, a large study that showed an impressive response rate, averaged to about…20%. And, if anything, the FDA gave it a conditional approval. As we heard from Dr. Vogel, it’s not really yet approved in Europe. And, of course, we heard also that pembrolizumab in a similar study also has shown quite promising data. If anything, there is a phase III trial for the nivolumab versus sorafenib that we’re still waiting for the data on, and this is in the first-line setting. Of course, there is also a phase III trial for pembrolizumab versus a placebo in the second-line setting. And this is not all—there is also a quite impressive combination of an anti-CTLA-4 plus anti-PD-1, durvalumab plus tremelimumab, which is happening in a phase III trial in 1200 patients in what’s called the HIMALAYA study. So, there’s a lot going on in that field. But let’s hear from Dr Kudo. So, what’s the story with the checkpoint inhibitors in Japan? What’s going on in regard to the whole field? Any approvals? Where do things stand?

Masatoshi Kudo, MD, PhD: Now, the Japanese FDA, PMDA (Pharmaceuticals and Medical Devices Agency), do not approve nivolumab. They do not follow the FDA, but Taiwan follows the FDA, and it was approved. But in Japan, we are waiting for phase III data.

Ghassan K. Abou-Alfa, MD: I see. In practice, is this an excitement that everybody really wants a checkpoint inhibitor, or is it still kind of like a measured response to that interest?

Masatoshi Kudo, MD, PhD: What do you mean?

Ghassan K. Abou-Alfa, MD: I’m saying, are people really very interested, super excited about checkpoint inhibitors, or is it still kind of like it is?

Masatoshi Kudo, MD, PhD: Yes, yes. Patients are very…

Ghassan K. Abou-Alfa, MD: More astute.

Masatoshi Kudo, MD, PhD: Waiting for that.

Ghassan K. Abou-Alfa, MD: Absolutely.

Masatoshi Kudo, MD, PhD: But for physicians, a little bit, monotherapy is not enough.

Ghassan K. Abou-Alfa, MD: I see, I see.

Masatoshi Kudo, MD, PhD: So, we are waiting for the combination.

Ghassan K. Abou-Alfa, MD: Fair enough. Again, to clarify, nivolumab in the United States is conditionally approved by the FDA. This is a conditional approval that is pending the phase III trial. In other words, if for whatever reason, God forbid, the phase III trial will be negative for nivolumab versus sorafenib, then it might lose that approval. But at this point in time, it is really approved based on that condition. So, we’ll see where it’s going to take us. And, of course, this is based on the promising data that came from the phase II study. This, if anything, reminds me to talk about the fifth drug that Rich already mentioned, which is cabozantinib. If anything, I had the honor on behalf of all the other colleagues to present the data at the GI ASCO, where a phase III trial of cabozantinib versus placebo showed a clear improvement in survival of more than 10 months in regard to the cabozantinib versus placebo. And it was statistically and clinically significant and, of course, will probably lead to a new standard of care. Of course, these data are from a study that I was heavily involved in. Of course, I’m very excited, but I would love to hear what my colleagues will say about that. Let’s start with Dr. Vogel. How was it? What do you think?

Arndt Vogel, MD: It was a great presentation, but I think the data were also very interesting. This was a well-performed trial, and the data were in line with what we expected. So, the placebo group was around 8 months median overall survival, which is in line with what we have seen before, and then the 10.2-month improvement was with cabozantinib. I think these are very good data, and I think there are some points that are also important to mention.

First of all, we did not have this patient selection. Patients were able to start the trial even if they were intolerant to sorafenib, which was different from the regorafenib trial. And I think what is also interesting in this trial is that patients with third-line therapy were included. So, I think around one-third, if I remember correctly, were treated with a third line of treatment. And when we looked just at the population of patients in the second-line setting, I think it was even more than 11 months’ survival. I think the indication here is very clear that it’s an active drug that significantly improved overall survival. PFS data were also very impressive: 1.9 months to 5.4 months, I think, so twice as long the PFS. So, this is an active drug. And from what I hear and from colleagues, the tolerability is also quite good, different than sorafenib. And even patients who do not tolerate sorafenib might tolerate cabozantinib, so I think this is a very interesting second-line option.

Ghassan K. Abou-Alfa, MD: I totally agree with you. If anything, really from my hands-on experience, the drug is very easy to handle and well tolerated.

Transcript Edited for Clarity

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