Future of Treating mRCC

Daniel J. George, MD: The last question I want to get to is about the future. What excites you the most for the next big thing in renal cell carcinoma? It could be a frontline treatment, it could be second line, it could be a new drug, or it could be a study. Anybody? I want to hear from all 3 of you, but what you are most excited about for 2021 ASCO, or beyond, in renal cell carcinoma? Monty, do you want to start? You’re smiling. You’ve got something.

Sumanta K. Pal, MD: Sure. We covered it at the time: Rana had mentioned glutaminase inhibitors.There are a lot of exciting target compounds emerging for the disease. I wanted to give a shout-out to a study that 1 of my former fellows from City of Hope wrote. He’s now in Brazil, Paulo Vergueiro. He wrote this beautiful trial looking at nivolumab-ipilimumab in combination with a probiotic. We’re most of the way through enrollment for this single-institution study, but I’m hoping we’ll see more of that: Trials that come out that try to hinge on other elements of RCC biology, acknowledging that hitting 1 target isn’t necessarily going to work for every patient’s disease. This is a study that randomizes patients to either nivolumab alone or nivolumab-ipilimumab combination with this unique oral probiotic that increases beneficial species with the gut—things like Bifidobacterium and Akkermansia—and they may promote nivolumab-ipilimumab’s activity.

Daniel J. George, MD: That’s fascinating. You’ve published some great work in this area, and again, this is recognizing that there are unappreciated interactions between the host and these drugs as well as ways to manipulate it. That’s cool.

Rana, do you have a favorite out there? Maybe it’s going to be to your trial with radium, I don’t know.

Rana R. McKay, MD: That’s a good point. We’ve got radium-cabozantinib, with or without radium, for people with bone metastasis and RCC, looking at introducing a radio-pharmaceutical in the solid tumor space beyond prostate cancer. That trial is currently enrolling through the Alliance for Clinical Trials in Oncology. You brought up an interesting point about patterns of progression and the use of focal therapy, as well as working through the NRG on a focal therapy trial for progression post–I/O. There is an opportunity for the integration of multiple modalities and different mechanisms of action.

We know the new kids on the block with MK-6482. I’m excited to see how that’s going to show in clinical trials. It is probably 1 of the most tolerable agents out there, barring some anemia and hypoxia, which are easily reversible. It’s exciting to see the novel mechanisms of action of the growing list of new agents that are currently in testing.

Daniel J. George, MD: Fantastic. Neeraj, do you have a favorite up there?

Neeraj Agarwal, MD: I’d like to add that, in the immediate future, I’m looking at the approval of cabozantinib with nivolumab. I’m sure the data will be impressive, so I cannot wait to see those PFS, OS, and hazard ratio data, knowing that cabozantinib is the best TKI among all the TKIs for metastatic RCC.

Another trial I feel excited about, having used high-dose interleukin-2 for many years, is for the NKTR-214 drug, which is the PEGylated interleukin-2. That is being tested, as we know, in different trials with NKTR-214 plus nivolumab versus control arm, oral cabozantinib versus oral sunitinib. The control arm also includes cabozantinib.

There is another trial with NKTR-214 plus ipilimumab, plus nivolumab versus ipilimumab-nivolumab. The trial is already moving forward. These trials will hopefully give us higher complete responses that will be more durable.

Looking at the history of high-dose interleukin-2, I’m looking forward to higher CRs and more durable complete responses with this combination.

Daniel J. George, MD: Fantastic. Thanks to all of you for this rich and informative discussion. Before we conclude, I’d like to get final thoughts from each of you. First Neeraj, any final thoughts?

Neeraj Agarwal, MD: We can talk about all the data we can, but what it really comes down to is treatment decision-making. As Rana said earlier, patients’ wishes, patients’ preferences, and patients’ view all affect how the disease should be treated. Keeping that in mind, immunotherapy combinations and VEGF-TKI plus immunotherapy combinations are playing a huge role in fulfilling those wishes for our patients.

Daniel J. George, MD: Fantastic. Rana, any thoughts on your end?

Rana R. McKay, MD: The treatment landscape for advanced RCC has been rapidly changing. The paradigm has been shifting over the last decade and a half. Patients are living longer, and they’re living better, but we still have a lot of work to do. There are still gaps in where we are with treatment, so it’s been exciting to see these changes take place and be a part of that process. But until every person with RCC is cured, we still have work to do.

Daniel J. George, MD: Absolutely. Monty, you get the final word.

Sumanta K. Pal, MD: It’s a little wonky, and it’s something we didn’t talk much about today, but I would say to get genomic profiling done if you feel comfortable. At this point in time, it might seem to have more limited applicability of renal cell carcinoma versus lung cancer, but in terms of making the second-, third-, and fourth-line decisions based on biology, we can look for the usual suspects like poor pathway alteration.

I just saw a paper pop up today that suggested that 20% of renal cell patients have DNA damage-repair alteration. Down the line, it’s going to be useful to have those genetic bits of data in your back pocket, as Rana mentioned, especially for non–clear cell.

Daniel J. George, MD: Fantastic. Thank you all again, and thanks to our viewing audience. We hope you found this OncLive® Peer Exchange® discussion useful and informative.

Transcript Edited for Clarity