Dr Voss on Cabozantinib Plus Nivolumab and Updated NCCN Guidelines in RCC

Martin H. Voss, MD, genitourinary medical oncologist, clinical director, Genitourinary Medical Oncology Service, Memorial Sloan Kettering Cancer Center, discusses key updates to the National Comprehensive Cancer Network (NCCN) clinical practice guidelines for kidney cancer, highlighting a phase 2 clinical trial (NCT03635892) of cabozantinib (Cabometyx) plus nivolumab (Opdivo) in patients with renal cell carcinoma (RCC).

The July 2024 NCCN guidelines update moved the single-arm study’s investigational combination to a preferred regimen for those with metastatic stage IV or relapsed non–clear cell RCC (non-ccRCC), Voss begins. The trial enrolled 40 patients with papillary, unclassified, and translocation-associated RCC, as well as a separate cohort ofpatients with chromophobe RCC, he explains. The rationale for evaluating chromophobe RCC separately stems from its distinct immune biology, which may require a unique therapeutic approach, according to Voss. All patientsreceived cabozantinib plus nivolumab at FDA-approved doses, with the option of a biweekly dosing schedule per label extension, he reports. None of the patients had received prior treatment, and all had measurable disease.

The primary end point was objective response rate (ORR), and the efficacy signal with the combination therapy was strong, Voss notes, particularly among patients with papillary RCC, where the ORR was 48% (95% CI, 31.5%-63.9%). Although the complete response (CR) rate was low, there were still some CRs, and the upfront disease progressionrate was minimal, he cites. However, the results in chromophobe RCC were less promising, with none of the 7 patients achieving an objective response and most experiencing some degree of disease progression, Voss reports.

Despite the disappointing outcomes in the chromophobe population, the trial met its primary end point for the non-chromophobe cohort, demonstrating robust efficacy with the cabozantinib/nivolumab combination, he states. These findings align with earlier studies investigating similar combination strategies, Voss notes, adding that the safety profile was consistent with expectations for frontline RCC treatment. The NCCN has now endorsed multiple combination strategies for the management of non-ccRCC, recognizing their potential across various RCC histologies, although they do not recommend one regimen over another, he concludes.