Ghassan K. Abou-Alfa, MD: I may be speaking a little out of sequence, but let’s talk about checkpoint inhibitors in hepatocellular carcinoma. Mark, why should we consider using immunotherapy in HCC?

Mark H. O’Hara, MD: There’s some definite interest surrounding the fact that in viral-mediated cancer, there seems to be increased antigen expression and a propensity that the immune system can be activated. From that perspective, we are trying to use immunotherapy in a viral-mediated cancer. In clinical trials, we have found that it doesn’t have to be virally mediated to actually have a response earlier in stable disease.

Mark W. Karwal, MD: It will go away by itself every now and then. This occasionally happens in renal cell cancer, suggesting that there is an immune-attacking component in your body.

Ghassan K. Abou-Alfa, MD: Fair enough. Based on that, there was an interest from the perspective of the inflammation/viral infection, but there was also a concern. Ultimately, the efforts in HCC caught up with the efforts in other diseases and we went ahead. There are many trials that have looked into checkpoint inhibitors in HCC. Among these trials, nivolumab was approved. Ruth, how was it approved?

A. Ruth He, MD, PhD: It’s a quite interesting story. Most of the drugs, in previous time, had to demonstrate survival benefit in a phase III trial. This, however, is based on a phase I/II study. We saw an amazing durable response with the immune checkpoint inhibitor in HCC. Initially, the study was a phase I small cohort study. It generated a 20% response rate. Then an extension cohort was done. That included about 200-plus patients, and the response rates held true in all 3 subgroups, or arms: patients with hepatitis B, those with hepatitis C, and those who were nonviral. The duration of the response is quite amazing.

These data were presented to the FDA and have led to the accelerated approval of the therapy, pending the phase III study that has now been completed. Now, we’re following up on the data.

Ghassan K. Abou-Alfa, MD: That brings us back to the point that we started with: Response, at the end of the day, is a very important focus. Of course, patients and physicians would really like to see a benefit. The response rates average around 20% with the use of nivolumab in second-line HCC. We went ahead and gave that conditional approval, pending the further evaluation of the drug in a study that’s looking at nivolumab versus sorafenib in the first-line setting. And so, until then, however, nivolumab is accessible and is an amiable option for your patients.

Transcript Edited for Clarity.