Dear readers,

At The Uromigos Live 2024 meeting, Drs. Rini, Powles, Albiges, McDermott, and Hammers discussed how to approach treatment for patients with non-clear cell (or variant) renal cell carcinoma. These cases are challenging. Unfortunately, our field has treated all variant histology as one entity when, in fact, they are very separate diseases with different biology and prognosis. Until very recently, single agent VEGF TKI was the front-line treatment with the most/best data supporting its use. However, both Cabozantinib and Nivolumab (Cabo/Nivo) as well as Pembrolizumab and Lenvatinib (Pembro/Len) look very promising for the treatment of variant RCC. Cabo/Nivo had a mPFS of 13 months, ORR of 48%, and mOS of 28 months. Pembro/Len had a mPFS of 17.9 months, ORR of 51%, and mOS (not reached). These are single-arm phase II trials so we must interpret them in this context. Now SUNNIFORCAST with ipilimumab and nivolumab (Ipi/Nivo) had a more modest PFS of 5.52 months, ORR of 32.8%, and mOS of 42.4 months (ORR and mOS higher than standard of care arm, which was mostly TKI monotherapy).

We CANNOT compare these trials. However, they all support use of immunotherapy in variant RCC. In patients with papillary RCC, I am using Cabo/Nivo or  Pembro/Len. Chromophobe patients were not treated with the Cabo/Nivo study, so I use Pembro/Len now in this disease, though one could make an argument to try Ipi/Nivo first and then salvage with lenvatinib + everolimus.

The treatment landscape is complicated for variant RCC. We need more data and more targets. My takeaway is emerging data suggests a role for checkpoint inhibitors in this disease and this is exciting for our patients!

Best,

Ben Garmezy, MD