Dr Westbrook on Clinical Trials That Have Shaped the Non-ccRCC Treatment Paradigm

“A lot of [oncologists] have experience using nivolumab plus cabozantinib in ccRCC. For many [oncologists who manage non-ccRCC], that combination might be their first choice, so it’s familiar. [However], in terms of the strength of the evidence, CA-209 9KU is a small study.”

Thomas Westbrook, MD, assistant professor, Department of Internal Medicine, Rush University, discusses the research in non–clear cell renal cell carcinoma (non-ccRCC) that informs his clinical practice.

The phase 2 CA-209 9KU trial (NCT03635892) was a single-center trial that enrolled 47 patients with non-ccRCC—a significantly smaller population number than those studied in trials such as the phase 2 KEYNOTE-B61 (NCT04704219) or SUNNIFORECAST (NCT03075423) studies, Westbrook begins. Although the combination investigated in CA-209 9KU, nivolumab (Opdivo) and cabozantinib (Cabometyx), is familiar to many oncologists and may be a first-line treatment choice for patients with ccRCC, the strength of evidence from CA-209 9KU is limited due to its noncomparative design and small sample size, he explains. This limitation is particularly evident in the data for rarer non-ccRCC subtypes, such as chromophobe RCC, he notes. Seven patients with chromophobe RCC were initially included in the trial, but data from this cohort were not consistently reported in subsequent updates, he says.

Despite these limitations, the CA-209 9KU regimen remains a viable treatment option, he reports. However, the KEYNOTE-B61 trial of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) has demonstrated more robust data than CA-209 9KU, according to Westbrook. This single-arm trial enrolled 158 patients with non-ccRCC, including chromophobe (n = 29), papillary (n = 93), and unclassified (n = 21) disease subtypes. The larger sample size and broader representation of histologic subtypes in KEYNOTE-B61 resulted in narrow confidence intervals and relatively reliable findings, he states. The trial reported a median PFS of 18 months (95% CI, 14-not reached), with insufficient follow-up data to determine the median overall survival, he explains.

Cross-trial comparisons between CA-209 9KU and KEYNOTE-B61 are unreliable due to differences in the trials’ baseline patient populations, Westbrook emphasizes. However, the KEYNOTE-B61 regimen has emerged as a preferred non-ccRCC treatment option for many oncologists, he says, although nivolumab plus cabozantinib may also be considered.