Tian Zhang, MD, MHS, provides an overview of the treatment of patients with non–clear cell renal cell carcinoma.
Tian Zhang, MD, MHS: There are many different types of non–clear cell [NCC] kidney cancer, so often we're bucketing them together. They come in several different histology, the most common type of NCC is a type that we call papillary kidney cancer, which has now actually been separated into Met-driven or a second type called fumarate hydrated loss, or FH loss, papillary kidney cancer. These are very different in their presentations. They tend not to metastasize so much, but they can certainly metastasize in certain situations. There are also subtypes called chromophobe, collecting duct, and medullary subtypes as well as translocation. So all of these are different subtypes of NCC kidney cancer that we really do need to study more in depth.
For a long time, our trials for therapeutics were run as basket trials in which we looked at papillary chromophobe and collecting duct all together and we saw the signals for VEGF [vascular endothelial growth factor] blockade. Sunitinib and imatinib but we also saw a particular subset of patients with chromophobe, for example, respond to everolimus-based treatments. In the most or more recent era, we've seen more trials that are very specifically focused on papillary kidney cancer. There was the SAVOIR [NCT03091192], in France thinking about savolitinib targeting the Met amplification part of papillary kidney cancer vs sunitinib that found in effect for savolitinib. That has now generated another trial called SAMETA [NCT05043090] and that is adding durvalumab in immune therapy on top of savolitinib.
In the United States, we also ran a papillary kidney cancer trial from my colleague Dr [Sumanta] Pal [, MD,] and his colleagues and the SWOG [the Southwest Oncology Group] cooperative group called PAPMET [NCTNCT02761057]. This was initially a 4-cohort study. It became a 2-cohort study and ultimately found an effect of cabozantinib given for metastatic papillary cancer. Now, that has also set up a trial further for PAPMET called PAPMET2 [NCT05411081], where patients are randomized between cabozantinib vs cabozantinib with atezolizumab. And then finally, recently, we've had a couple of trials report out. There was a basket trial for NCC kidney cancer that was treated with lenvatinib and pembrolizumab. We did see some effects in both papillary chromophobe and unclassified as well as translocation. There were some partial responses [of approximately] 50% in each of these subtypes. So we are starting to come to a place where we have more and more options for each of these subtypes of NCC kidney cancer.
Transcript is AI-generated and edited for clarity and readability.