CheckMate 9ER: Phase 3 Trial of Frontline Nivolumab + Cabozantinib

Daniel J. George, MD: It almost seems like every quarter there's a new regimen that’s coming out that’s showing excitement.

Monty, in April of this year, amid all the COVID-19 [coronavirus disease 2019] stuff and everything else we had going on, CheckMate 9ER had a press release showing a positive progression-free survival [PFS] and overall survival benefit to that. Of course, we haven't seen the data, but with first impressions from that press release and what you know about that regimen, what's your take on that? Is that going to be a viable option in this frontline space?

Sumanta K. Pal, MD: It’s impressive. My sense was that, after bevacizumab/atezolizumab came out, all the VEGF/IO [immune-oncology] regimens to emerge thereafter would face an uphill battle. If you’re competing against sunitinib, you’re going to have more and more patients who get upfront an VEGF inhibitor cross over and get second-line immunotherapy, then that would certainly make an overall survival bar even higher. Seeing CheckMate 9ER emerge with this impressive signal for overall survival and PFS advantage is incredible. I can't wait to see the numbers.

To a question that you asked earlier, what sort of follow-up are you going to need to see with some of these studies? I’d have to tell you that that may be contentious in the context of some of these emerging studies. With a regimen like the one they assessed in CheckMate 9ER with cabozantinib and nivolumab, I can definitely think of places where I'm going to want to use it up front, irrespective of the fact that it doesn't have substantial follow-up or won't have substantial follow-up at the time of the initial report. For those patients with bone metastasis and those patients with aggressive disease that were cast under the CABOSUN trial umbrella, those are folks that I’d probably want to preferentially treat with cabozantinib/nivolumab up front.

Daniel J. George, MD: When I look at those Kaplan-Meier overall survival curves, it doesn't matter if it's CheckMate 9ER, we haven't seen that one yet, but CheckMate 214 or KEYNOTE-426. What's impressive is the separation of these curves early on and within the first 12 months. That’s impressive because, remember, these are clinical trial patients. These are patients who met eligibility for clinical trials who had reasonably good performance status. They were intermediate- or high-risk, yes, but they were able to go on study, yet within 12 months, we see 25% of these patients in the sunitinib arms dying of disease. It tells you, as a quarter of this population is dead at 12 months, the immediacy of picking our best regimens. The separation of those curves early on in those first 6 to 12 months tells you that, for the sickest patients, these regimens are making a huge impact. You could talk about whether there's crossover and everything, but for these patients, there is no time for crossover. For these patients, making the first best decision is critical because they may not have a second-line therapy. We're going to talk about second-line therapy in a minute.

Transcript Edited for Clarity