Rana R. McKay, MD: I do think that the retrospective studies fill a gap in our current data. The CARMENA and SURTIME trials don’t actually reflect the current practice patterns. They were conducted during the TKI [tyrosine kinase inhibitor] era. They were done in the context of patients receiving sunitinib therapy. Our frontline treatment options have dramatically changed over the last several years, with the introduction of I/O [immuno-oncology]—I/O and I/O-VEGF combinations. I think the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] is able to fill that gap by highlighting real-world data of patients who are receiving I/O therapy and looking at the role of cytoreductive nephrectomy in patients who are receiving more modern therapy.

While there’s bias with retrospective data, there’s huge selection bias as to why that individual underwent a cytoreductive nephrectomy to begin with. I think it’s balanced by the bias that’s present in the trials. It’s not to say a person shouldn’t have received a cytoreductive nephrectomy, but there wasn’t a huge push to get that person to undergo a cytoreductive nephrectomy. There was the opportunity to be randomized, and the surgeon and the medical oncologist and treating team felt comfortable with that randomization. And so I do think that these data certainly fill a gap. It’s exciting to see how far the IMDC has come, and the information that we’ve been able to garner from this large international cohort of metastatic RCC [renal cell carcinoma] patients.

Ulka Vaishampayan, MD: Yes, I agree with you, Rana. Real-world data are very useful and informative, in terms of designing future trials within this arena. I also want to discuss the PROBE trial. This is a phase III clinical trial looking at sequencing with I/O combination therapy followed by either doing cytoreductive nephrectomy or continuing systemic therapy. This is a SWOG study, for which we are currently writing the protocol, and it will likely be available for accrual fairly soon. There are other randomized trials that are also looking at the similar question of adding local therapy to the primary tumor, along with contemporary systemic therapy. Tian, do you want to discuss those?

Tian Zhang, MD: Sure, absolutely. NORDIC-SUN is 1 of these trials. It’s a phase III randomized trial of ipilimumab-nivolumab up front. Then patients are randomized to receive either a cytoreductive nephrectomy or no nephrectomy. Patients will be stratified by IMDC risk, and the primary outcome is overall survival. The number needed to enroll is about 400, and the study is currently ongoing. It is based in Denmark.

The other study that we highlighted during our recent Twitter chat was CYTOSHRINK, and this is a phase II trial of, again, the ipilimumab-nivolumab combination for these patients. However, this is premised on the fact that radiation might potentially release tumor antigens to allow the immune checkpoint inhibitors to work better. And so after 1 cycle of ipilimumab-nivolumab, these patients will receive stereotactic radiotherapy to their primary tumor followed by the second cycle of ipilimumab-nivolumab, according to standard care. This trial is a 2:1 randomization, with a number needed to enroll of about 78. The trial is currently ongoing, with a primary end point of progression-free survival.

Transcript Edited for Clarity