Daniel J. George, MD: Monty, any thoughts on your steroids use in these patients? Do you use steroids the same way when you’re dealing with an immune-related AEs for say ipilimumab/nivolumab versus an immune-related AE for say pembrolizumab/axitinib? Is there any difference in how you use the steroids in those different scenarios and discontinuing and restarting drugs in those scenarios?

Sumanta K. Pal, MD: I wish I could give you something nuanced for the process of management. I find that I am quite similar in my strategy for both. I start with Solu-Medrol or prednisone, maybe in the context of some GI or liver-based toxicity from the drugs. Perhaps in the context of nivolumab/ipilimumab, I’m a bit more liberal in jumping to the second-line therapy just because we’ve all seen situations where it’s significant.

Daniel J. George, MD: That’s fair. I feel the same way: for the combination of IO/IO, you can’t reverse that. With the IO/TKI [tyrosine kinase inhibitor], we would hold the TKI, so it’s going to wash out. It may take a few days, or it may take a week, but it’s going to wash out. With the IOs, they’re not necessarily going to wash out. For a lot of these toxicities, they sometimes happen with the very first dose, but more often, it’s with that second or third cycle, so you’ve loaded them up, and that’s going to take awhile. I think about treating with steroids a bit longer in those courses, and I think about what you said: moving on to the second-line agent a little bit sooner if we’re not seeing the results. Those drugs work much better if we do them earlier rather than later. That’s helpful advice.

Finally, are there patients who you would look at up front and say that they are not an IO candidate? Are there criteria? You mentioned some of the things in the past that excluded them from trials, such as autoimmune conditions, but are there other factors or other things you’re concerned about with IO therapy that you would hesitate and consider using more straight TKIs?

Sumanta K. Pal, MD: Rana and Neeraj both alluded to this, but it’s when you have that sense or that gestalt that the patient is not going to be very compliant. Say, for instance, that the patient had their nephrectomy at your institution 10 years ago and then never went for a single follow-up scan, and they show up a decade later with extensive metastasis. That’s the individual for whom you may balk a bit. You have to have a certain level of trust between physician and patient to apply IO-based therapy.

Daniel J. George, MD: That’s exactly right. It’s challenging because you’re just getting to know these patients; they are new patients to us, and we are making a lot of important decisions up front and trying to get a sense of this. This is an important aspect to this.

Transcript Edited for Clarity