Selecting the Optimal Treatment Regimen for Favorable-Risk RCC


Experts on renal cell carcinoma discuss frontline treatment options for favorable-risk disease and factors that impact treatment decisions.


Elizabeth Wulff-Burchfield, MD: Dr McGregor, are there other regimens that you think need some airtime here with regard to these favorable-risk patients? Are you sending patients for high-dose IL-2 or single-agent TKI [tyrosine kinase inhibitor]? Anything else that we haven't covered?

Bradley McGregor, MD: I think it's a great discussion. I just want to highlight how far we've come in kidney cancer. If we look at that initial IMDC [International Metastatic Renal Cell Carcinoma Database Consortium data], the median survival for favorable-risk disease was 43 months. Now we're looking at intent-to-treat, including poor-risk disease, and seeing median survivals of 48 months, or 4 years. With nivolumab-ipilimumab, the median survival for those with poor-risk disease was approaching 70 months. It's just amazing how far we have come. And I think how IO [immunotherapy] has changed and revolutionized kidney cancer is just critical.

Going back to my first answer, I think it's shared decision-making. We have so many options that are available. The TKI/IO options are great. I agree with Rana, nivolumab-ipilimumab certainly has a role. There's a numerical improvement in overall survival with extended nivolumab-ipilimumab vs sunitinib. There's that chance for that durable treatment-free interval. The objective response rate and the PFS [progression-free survival] certainly are better with sunitinib overall, but there's that group of patients [where] 10% to 50% get that CR [complete response] that can be really maintained. All of those factors come into play. It just involves that discussion with the patient. I agree with you, those are some of the most challenging discussions I have in the clinic. There are a lot of options.

We were fortunate to be part of a trial looking at the addition of belzutifan to cabozantinib in treatment-naive patients. That data have been presented. Response rate is close to 60% in the treatment-naïve, granted it was a small number of patients, but it’s a suggestion that maybe there are different combinations that we can use. We have data from [Michael Atkins, MD,] with single-agent nivolumab that showed response rate close to 60% in favorable-risk disease. It really is evolving.

There’s the question of if we cover all our bases, I think with favorable-risk disease you have options, we can do IO and then TKI. Is there a synergy between the 2 or is the sequential approach better? These are the questions that remain unanswered, and hopefully ongoing trials will help us better delineate.

Elizabeth Wulff-Burchfield, MD: I agree. Thank you so much. …[Does] anyone have additional key factors that drive selection of first-line therapy? Anything that hasn't been covered? You all have been pretty thorough in your responses, so we may have covered that.

Rana McKay, MD: I think maybe the only thing we didn't spend too much time on is just the role of metastasectomy and SBRT [stereotactic body radiation therapy] for people who have oligometastatic disease. There's been a renaissance in radiation therapy in RCC [renal cell carcinoma] largely because of more refined radiation techniques. We're able to deliver a higher dose per fraction and really overcome that historic notion that kidney cancer is a radio-resistant disease. We've actually seen a flurry of data of use of radiation therapy for oligometastatic disease. I think it's the favorable-risk patients that fit in that bucket more commonly. They've had their primaries excised, they've got low-level pulmonary nodules that you may have, in the context of sampling their lung nodule, had them do a VATS [video-assisted thoracic surgery], and you've already resected 50% of their disease. So I do integrate radiation therapy, and there will be a study through the cooperative groups called SOAR [Salvage Oligometastasectomy and Radiation] that will be looking at radiation therapy to oligometastatic disease.

Elizabeth Wulff-Burchfield, MD: Having that randomized data will be so rich. That trial design has been pretty challenging to refine and make sure [it] will answer the most important clinical questions that will impact future decision-making, but it'll be really meaningful to see that.

Transcript edited for clarity.

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