Insights From: Arndt Vogel, MD, Hannover Medical School; Oliver Waidmann, MD, Goethe-Universitat Frankfurt am Main
Oliver Waidmann, MD: One novel approach is ramucirumab. It is an antibody of VEGF receptor 2. It’s an interesting drug, because it’s active. We know it from colorectal cancer, we know it from non–small cell lung cancer, and we know it from gastric cancer. It’s active and it doesn’t have that many side effects. We know it from former trials in HCC that only patients with high AFP levels, higher than 400 ng/mL, benefit from the treatment. And now it’s tested in a phase III trial compared with placebo in a 2:1 fashion, and we’re quite curious to see the data.
Combination therapies are also a really good question in HCC. We had some trials that were negative because, I think in my opinion, it was the problem that we combined 2 toxic agents and we saw, in the end, even more toxic problems. We know that erlotinib, which is really active in patients with pancreatic cancer and also in patients with lung cancer, is targeting the EGF receptor pathway. It was combined together with sorafenib, and we had no more efficacy but we had much more side effects. This was a problem. I think the way to go is not combination of TKIs or small inhibitors, but it’s combination of immunotherapy. So, we can combine checkpoint inhibitors such as PD-1 antibodies and CTLA-4 antibodies. We have some data we’ll see probably soon on nivolumab and ipilimumab. And I think there were data presented with tremelimumab and durvalumab. Durvalumab is a PD-L1 antibody and tremelimumab is a CTLA-4 antibody. And this was effective in the first trial, so we saw response rates.
The second option will be to combine a checkpoint inhibitor or immunotherapeutic agent together with small molecules. We know from colon cancer that MEK inhibitors, for example, can sensitize tumors to immunotherapy. So, we know that the MEK inhibitor, and also a checkpoint inhibitor, leads to responses in patients with colorectal cancer, which are microsatellite stable and normally do not respond to immunotherapeutics.
It was a really hard way for everyone who is treating HCC, so we had really many, many trials that were negative and now we have immunotherapy, which is also exploding, we can say, in the world. We have new drugs. We are really lucky that we can now treat the patients with effective drugs. If we use immunotherapy, we have drugs that don’t have that many side effects as before. So, I think we will now have to identify the patients who will benefit from immunotherapy and who won’t. And we will also have to find ways to get patients not sensitive to the immunotherapy if it’s combined with different drugs. I think this will happen in the next few years and I’m quite happy and lucky that we can also participate in this.