Cabozantinib Plus Nivolumab in Adult Patients with Advanced or Metastatic Renal Cell Carcinoma: A Retrospective, Non-Interventional Study in a Real-World Cohort/GUARDIANS Project.

Simple Summary: ICI-based combinations have led to a significant change in mRCC medical treatment. However, data from real-world (RW) cohorts are rare. In this multicenter study, we evaluated the safety and effectiveness of cabozantinib plus nivolumab in real-world cohorts from centers in Germany, Switzerland, and Austria. The median PFS in the overall cohort was 18.6 months. We also analyzed subgroups in relation to the IMDC, histology, and with regard to the presence of bone metastasis. In summary, our real-word data support the promising efficacy data of the pivotal trials, particularly in patients with non-ccRCC and those without bone metastases at the start of the treatment. Introduction: Combinations of immune-checkpoint inhibitors (ICIs) are the standard of care (SOC) for treatment-naive metastatic renal cell carcinoma (mRCC) patients. In this multicenter study, we evaluated the RW safety and efficacy of cabozantinib plus nivolumab in mRCC patients. Methods: Data were retrospectively collected from twelve cancer centers in Germany, Switzerland, and Austria. Patients with advanced or mRCC were eligible. The investigator-based objective response rate (ORR) and progression free survival (PFS) were calculated from the start of the treatment to progression or death. Descriptive statistics and Kaplan–Meier (KM) plots were utilized where appropriate. Results: In total, 96 eligible patients (66.6% male) with a median age of 66.0 years were included. The most common histology was clear-cell RCC (ccRCC) in 63.4% (n = 61). A prior nephrectomy was performed in 60.4% (n = 58). ECOG 0-1 was 68.8% (n = 66). A partial response was documented in 43.8% of patients (n = 42), a stable disease in 32.3% (n = 31), and a progressive disease in 8.3% (n = 8) as the best overall response. Response data were not evaluable in 13.5% (n = 13). The median follow-up time was 12.7 months (95% CI, 10.0–15.3). The PFS rate at 6 months was 89.8% in the overall population (86.8% for ccRCC; 90.0% for non-ccRCC). Adverse events (AEs) were reported in 82.3% (n = 79) for all grades and 41.7% (n = 40) for grades 3–5. Elevated liver enzymes (34.4%), diarrhea (31.3%), and hand–foot syndrome (29.2%) were the three most frequent AEs of any grade and causality. Discussion/Conclusions: In this real-world cohort of mRCC patients, the application of cabozantinib plus nivolumab was shown to be safe and feasible. Our data support the use of cabozantinib plus nivolumab as a first-line standard therapy in mRCC patients. Major limitations were the retrospective data capture and short follow-up time of our study. [ABSTRACT FROM AUTHOR]