Oliver Waidmann, MD: I think we are quite lucky that although we had a lot of negative trials, we still have trials in HCC in the second-line. I think there are 3 different drugs that we should discuss at least, or even 4. So, the first is ramucirumab. Ramucirumab is an antibody to VEGF receptor-2. It is approved. It has been shown to be active in lung cancer, in gastric cancer, and also in colorectal cancer, and now in the so-called REACH-2 study, which investigates ramucirumab in a second-line setting against placebo in a 2:1 fashion in patients who have elevated AFP levels. And I think the drug is somehow interesting because it was shown that in patients with really high AFP levels, higher than 400 ng/mL, they showed an overall survival benefit in patients with HCC. I think the side effects are quite manageable. It’s much better; there are much less side effects compared to TKIs. So, I think this is a good option if the study will be positive, which I don’t know.

The second interesting agent is nivolumab. It has been tested in the second-line setting in the CheckMate-040 study in patients with previous treatment, but also in the patients with previous sorafenib treatment. I will focus on these patients. We saw that patients had a really big improvement in overall survival: 13 months. It’s better than in other trials, and I feel it will be approved for HCC second-line treatment according to these data.

The third drug that I think is interesting—and we also have a phase III trial on—is cabozantinib. Cabozantinib is a multikinase inhibitor. It’s also targeting MET, so it’s not like tivantinib. Cabozantinib targets VEGF and other pathways. And it has been approved for kidney cancer. It’s effective in kidney cancer and also in medullary thyroid cancer. So, it’s an active drug in other diseases, and it will be tested in the phase III trial in the second-line or in the frontline setting. I’m quite curious to see the data from this study, but I think it hasn’t recruited completely, so we’ll have to wait a bit of time.

So, pembrolizumab is also a checkpoint inhibitor. It’s a PD-1 antibody that has been approved for other different diseases, including lung cancer. And it’s also investigated in the second-line setting in patients with HCC after sorafenib. I think the studies are recruiting, especially the randomized trial, and I will be quite curious to see if there’s a difference between nivolumab and pembrolizumab. But I also think this will be an active drug.

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