Dr Nguyen on Updated NCCN Guidelines for Non–Clear Cell RCC

“We don't have randomized data to just recommend and support new clinical trials for patients with non–clear cell kidney cancers. We have several randomized phase 3 studies that are ongoing that should hopefully be a meaningful contribution [to] data in this space, and hopefully we really improve the guidelines for this group of patients.”

Charles B. Nguyen, MD, assistant clinical professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses the updated 2024 National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for non–clear cell renal cell carcinoma (RCC) and their effect on treatment decision-making.

Randomized data are still lacking to drive treatment decisions for the non–clear cell RCC popilation, Nguyen begins. Therefore, there isn’t a category 1 preferred regimen to treat non-clear cell RCC. Otherwise, 3 preferred regimens include cabozantinib (Cabometyx) monotherapy, cabozantinib plus nivolumab (Opdivo), and lenvatinib (Lenvima) plus pembrolizumab (Keytruda), he explains; clinical trial enrollment is another preferred approach. Based on these preferred regimens, he says the combinations of cabozantinib plus nivolumab and lenvatinib plus pembrolizumab have raised the bar regarding response rates among patients with non–clear cell RCC. Although there are many single-arm phase 2 studies, he emphasizes the need for more randomized trials to further support the use of these regimens.

Data from a phase 2 study (NCT03635892) published in European Urology determined that cabozantinib/nivolumab demonstrated efficacy and sustained responses in patients with non–clear cell RCC. Specifically, at a median follow-up of 34 months (range, 20-51), combination led to an overall response rate of 48% (95% CI, 32%-64%) in this patient population (n = 40).

Based on the NCCN’s updated guidelines, Nguyen emphasizes that recommending and supporting new clinical trials for this patient population is crucial because there aren’t randomized data in the space. Nevertheless, he concludes that there are several phase 3 randomized studies ongoing that will hopefully contribute meaningful data to improve treatment guidelines for patients with non–clear cell RCC.