Darren S. Sigal, MD: So, right now, in the second-line setting, we have 2 approved options. One is regorafenib, based on the RESORCE trial, and the other one is nivolumab, which is from the CheckMate-040 trial that we’re talking about now. There’s not any one right predictor of response. There are no markers that suggest one treatment or the other would be more active. You need to look at the patient’s underlying comorbidity risk and risk for toxicities when you make those decisions. For significant underlying liver dysfunction, it may be better to start with a checkpoint inhibitor since regorafenib is known to occasionally cause significant liver dysfunction.

Catherine T. Frenette, MD: Can you comment about the use of immunotherapies in patients who potentially have autoimmune problems already or maybe patients who are going to go on to a liver transplant or have already had a liver transplant?

Darren S. Sigal, MD: This is a very hot area of debate and, I’m sure, research interest. The 2 points you brought up, one is related to patients with underlying autoimmune disease and the second one is patients who are going to be transplanted or have been transplanted. And so, there are no data. The studies that use checkpoint inhibitors excluded patients with autoimmune disorders. This is something that should only be used very, very selectively, if at all. In terms of transplant candidates or patients with transplant, again, it probably should be avoided at this point in time because the immune milieu of the liver is complicated, and there are case reports in other organ transplant settings where immune checkpoint inhibitors have led to graft failure.

Catherine T. Frenette, MD: I think this is a very important thing to think about when we’re talking about the different options for our patients.

Transcript Edited for Clarity