Brian I. Rini, MD:What would you do next for this patient? Let me throw out some options, but obviously you could do whatever. You could say, “Well, boy, I stopped pembrolizumab and something bad happened. Why don’t I just restart pembrolizumab?” Or [say,] “You know what? This patient has hepatic progression, that’s bad. And the consequences of further progression are bad. I’m going to switch therapy to, call it cabozantinib.” Or I’ll put cabozantinib [plus] atezolizumab in there as a teaser to talk about the CONTACT-03 [trial]. Stephanie, why don’t we start with you? What would you choose for this patient? New hepatic metastases, nice response to axitinib [plus] pembrolizumab, stopped pembrolizumab, and now you have some progression.

Stephanie A. Berg, DO: This has been 2 and a half years post IO [immunotherapy], or a year and a half?

Brian I. Rini, MD:No, 2 and a half years post start of therapy.

Stephanie A. Berg, DO Oh, start of therapy.

Brian I. Rini, MD:So about 6 months after stopping IO.

Stephanie A. Berg, DO I do recognize the fact about IOs and what Dave Braun, [MD, PhD,] was saying about how many of the receptors are being taken up by the drug. At this point, you would assume that probably is not in their system anymore. For this patient, especially with sarcomatoid histology, I would want to restart their IO.

Brian I. Rini, MD:You’d be tempted to restart their IO and see what happens.

Stephanie A. Berg, DO I would be tempted to restart it.

Brian I. Rini, MD:Fair enough.

Stephanie A. Berg, DO Yes.

Eric Jonasch, MD: It’s tempting, but again, I think the board answer and the community answer would be single-agent cabozantinib for this patient. But again, I think, what would happen if you were to give both? And do you need both? So maybe what you can do is you can start with cabozantinib, and you can layer in an IO if you’re not getting the response you need. But it’s a data-free zone, and I think both are reasonable strategies.

Brian I. Rini, MD:Fair enough.

Stephanie A. Berg, DO I’ll share an anecdote. I had patient…with the same situation, having stopped the IO, and I restarted pembrolizumab and switched to lenvatinib. So gave lenvatinib [plus] pembrolizumab, and he did really well for quite some time on that. It scratches the itch of wanting to restart the IO because you stopped it, and maybe that was the culprit, but also bringing in your powerful liver metastasis combination.

Brian I. Rini, MD:And you did both at the same time.

Stephanie A. Berg, DO: Yes.

Brian I. Rini, MD:Yes.

Stephanie A. Berg, DO: At tumor board, I was the only vote for that, but I tried it, and it worked.

Brian I. Rini, MD:It was your patient.

Stephanie A. Berg, DO: It was. Right.

Brian I. Rini, MD: It was the only vote that mattered. Bruno, what do you think? What would you do here?

Bruno R. Bastos, MD: The answer is, if you want to go to the guidelines, it would be cabozantinib as a single agent. However, the reason I’m saying this is because you may face insurance approval issues to restart immunotherapy. I’ve faced this situation before, but I would make a case that this patient needs to be reintroduced to the IO therapy. I would pick a different IO/TKI [tyrosine kinase inhibitor], I would be favoring the use of…some combination like cabozantinib [plus] nivolumab in this situation because I believe there is some role for IO. I would not pick ipilimumab because of the rheumatoid arthritis history, but definitely one of the PD-1 inhibitors I would reintroduce.

Transcript edited for clarity.