"Unfortunately, I don't think that the triplet of cabo/nivo/ipi is ready as the current dosing for use in RCC with variant histology," says Bradley McGregor, MD.
In this video, Bradley McGregor, MD, discusses the 2023 American Society of Clinical Oncology study, “Phase II study of cabozantinib (Cabo) with nivolumab (Nivo) and ipilimumab (Ipi) in advanced renal cell carcinoma with variant histologies (RCCvh).” McGregor is director of clinical research for the Lank Center for Genitourinary Oncology and instructor in medicine at Harvard Medical School, Boston Massachusetts.
When we think about renal cell carcinoma, there's really been a ton of advances in treatment, although a lot of those are been relegated to clear cell renal cell carcinoma, which is the most common type of kidney cancer, accounting for 80% of renal cell carcinoma. But we know there's 20% of patients who present with RCC with variant histologies, formerly called non clear cell. And we really have been looking to make advances in that field. For a long time, it's been incremental advances. There had been some really exciting advances recently, but we were really building upon what we saw with COSMIC-303 nivo/ipi/cabo vs nivo/ipi, try to bring that triplet into the RCC with variant histology. This was a single-arm phase 2 trial called the CaNI trial, which took 40 patients with renal cell carcinoma variant histology, who had received up to 1 prior therapy. We have about 10-month follow-up and are excited to present the first results. And so we had enrolled 40 patients; a majority of these patients were papillary renal cell carcinoma, although we did have 11 patients with chromophobe renal cell carcinoma. And what we saw overall, was a response rate of 18% per RECIST, certainly lower than we would have hoped, with minimal responses in chromophobe histology. And this came with significant toxicities; over 40% of patients required high-dose steroids, and there were marked LFT abnormalities as well. I will caution, though, this is only 10 months of follow-up. If you look at the waterfall plot, 14 of the 40 patients remain on therapy. And a lot of those patients on immunotherapy have tumor shrinkage; it just hasn't quite reached that 30% mark. And so I think for the follow-up it will be critical to really understand the results of what we've seen so far. This is a Herculean effort. And unfortunately, I don't think that the triplet of cabo/nivo/ipi is ready as the current dosing for use in RCC with variant histology. I think we need to better understand which histologies actually do respond. That work is ongoing.
This transcript was edited for clarity.