Dr Westbrook on the Potential Use of ccRCC Therapies in Non-ccRCC

Thomas Westbrook, MD, assistant professor, Rush University Medical Center, discusses the investigation of approved treatment options for patients with clear cell renal cell carcinoma (ccRCC) treatments in the context of non-ccRCC treatment.

The adaptation of therapies from the ccRCC treatment arena to the non-ccRCC therapeutic landscape have become standard practice, though responses vary significantly across disease subtypes, Westbrook begins. Notably, certain non-ccRCC subtypes, such as collecting duct carcinomas and renal medullary carcinomas, are more responsive to chemotherapy than most other RCC subtypes, he says. Despite this, treatments originally studied and used in ccRCC, including mTOR inhibitors, TKIs, and immunotherapies, are frequently tested in non-ccRCC, he explains. Some clinical trials have included all RCC subtypes, yet the non-ccRCC cohorts are often small, creating barriers to drawing definitive conclusions for disease subtypes such as chromophobe RCC, he notes.

Over time, the kidney cancer treatment field has developed increasing awareness that non-ccRCC entities should not necessarily be treated identically to ccRCC or even to each other, given the unique biological drivers across all subtypes, he emphasizes. Although response variability remains across subtypes, there have been notable successes with ccRCC therapies in non-ccRCC cases, he reports. Many non-ccRCC tumors exhibit sensitivity to TKIs and immunotherapies that have demonstrated efficacy in ccRCC, Westbrook states. The broader applicability of these agents may stem from multi-targeted TKIs, which inhibit multiple pathways and may effectively address various non-ccRCC tumors, he says. Thus, although non-ccRCC tumors have diverse biological profiles, their responsiveness to some ccRCC-derived therapies highlights the therapeutic potential of these agents in these subtypes and underscores the need for further research to optimize treatments based on individual tumor characteristics, he notes.

Regarding the National Comprehensive Cancer Network guidelines for the treatment of patients with non-ccRCC, the first recommendation is clinical trial enrollment, Westbrook explains. Preferred frontline regimens include cabozantinib (Cabometyx) as monotherapy and in combination with nivolumab (Opdivo), as well as lenvatinib (Lenvima) plus pembrolizumab (Keytruda), he says. Everolimus plus lenvatinib is a strong second-line regimen for patients who have not received upfront lenvatinib plus pembrolizumab, he concludes.