Transcript: Daniel J. George, MD: Now we’re entering a data-free zone, right? We’ve got these new studies, and they’ve been done in the frontline setting, and they’re changing our frontline landscape. Now we’re going to have to extrapolate the older studies that we’ve had. That data were done in an earlier time. They’re not all going to get redone, and they’re the best data we have. Help us understand a little, Joe. How do you apply the older studies to this setting of, say, progressing on nivolumab, ipilimumab, pembrolizumab, or axitinib?

Chung-Han Lee, MD, PhD: Right now, certainly we are limited to mainly retrospective studies. There have been multiple centers that have come together to try to look at this population. With a lot of these treatments being rather new, there have been collaborations between us, Memorial Sloan Kettering Cancer Center, and Nizar’s group in terms of looking at the effect of subsequent therapy after progression on immune checkpoint inhibitor combination.

We’ve also looked at what the outcomes are for TKIs [tyrosine kinase inhibitors] after you’ve progressed on the TKI/IO [immuno-oncology] combination. But it seems the prior therapies can still be affective in that setting. I think the studies have kind of supported that. There are certainly ongoing studies looking at the effect of TKI/IO combinations postprogression IO, and also immune checkpoint inhibitor combinations postprogression IO. But it will probably still take quite some time for those to read out.

Nizar M. Tannir, MD, FACP: What’s clear from those retrospective studies that Joe alluded to, is a recently published retrospective study of 70 patients from Memorial Sloan Kettering Cancer Center and The University of Texas MD Anderson Cancer Center, strictly in the second line, post nivolumab-ipilimumab and atezolizumab-bevacizumab. But the majority of the patients had either nivolumab alone or nivolumab-bevacizumab and nivolumab-ipilimumab. So the response rate was quite high, as if they had not received any first-line therapy, and it’s similar to first-line therapy we are accustomed to seeing with monotherapy with TKI—30% to 40% response rate, PFS [progression-free survival] in excess of 10 months. In that 70-patient retrospective study, the PFS was around 13 months and the response rate close to 40%. I think that’s impressive. If the patient did not receive any prior TKI, and they get treated with a second-line TKI, you’re going to see a higher response rate, which we would expect if they haven’t been exposed to a prior TKI.

And in that space, there is a trial that many of you are familiar with, the CANTATA trial, which is looking at cabozantinib plus an investigative agent, glutaminase 1 inhibitor versus cabozantinib versus placebo in the second-line, third-line space post IO. I think this is where we really need more trials, and this is where there is space to have trials in the post-IO data space.

Transcript Edited for Clarity