Dr Vento on the Role of IO/TKI Combos in Non–Clear Cell RCC

“For specific subtypes, such as papillary RCC, this notion of unclassified RCC or RCC not otherwise specified, and maybe even [in] chromophobe RCC and translocation RCC, this IO/TKI approach is a reasonable frontline treatment in the current setting.”

Joseph Vento, MD, an assistant professor in the Department of Internal Medicine at University of Texas Southwestern Medical Center, discussed the role of immuno-oncology (IO) plus TKI combinations as a treatment option for patients with non–clear cell renal cell carcinoma (RCC).

Currently, there are 2 large ongoing studies evaluating IO/TKI combinations, including a phase 2 trial (NCT03635892) examining cabozantinib (Cabometyx) plus nivolumab (Opdivo) in non–clear cell RCC, and the phase 2 KEYNOTE-B61 trial (NCT04704219) investigating pembrolizumab (Keytruda) plus lenvatinib (Lenvima) for the same patient population, Vento began. He noted that in both studies, patients have experienced promising overall response rates (ORRs) across a variety of non–clear cell RCC subtypes. Specifically, in patients with papillary RCC, unclassified RCC, RCC not otherwise specified (NOS), chromophobe RCC, and translocation RCC, IO/TKI combinations could be a reasonable treatment in the frontline setting, he explained. However, with more studies assessing molecular drivers in non–clear cell RCC, Vento added that it’s important to consider more specific factors in respective subtypes, such as MET-driven papillary RCC. With this consideration, utilizing MET inhibitors to target certain subgroups that would demonstrate responses could be a next step, he said.

Furthermore, in the chromophobe RCC space, Vento explained that there has been more translational research regarding pathways involved and whether targeting pathways involved with IL-15 for apoptosis. Nevertheless, he emphasized that it’s important to have reasonable frontline treatment for at least some subtypes of non–clear cell RCC with cabozantinib/nivolumab and pembrolizumab/lenvatinib that have produced higher ORRs. Still, additional work needs to be done in this space to investigate other approaches beyond IO/IO and IO/TKI combination, including other clear cell RCC regimens as options for patients with non–clear cell RCC, he concluded.