PurposeImmune-based (IO)-combinations are the backbone in the systemic therapy of metastatic renal cell carcinoma (mRCC). Despite phase III clinical trial data, real world data are of special importance to reflect clinical practice.MethodsThis retrospective study included 201 mRCC patients receiving first-line systemic therapy from January 2006. Clinicopathological and treatment-related data were recorded. Progression-free (PFS) and overall survival (OS) were analyzed using descriptive statistics and Kaplan–Meier analysis.ResultsOver the years, IO-based therapies have increased significantly. The collective comprises 76 patients with first-line IO-based therapy (IO-IO:55, TKI-IO:21) and 125 patients with TKI-monotherapy. PFS was significantly improved with TKI-IO combinations if compared to both TKI-monotherapy (23.9 vs. 10.3 months, HR 0.48,p= 0.034) and IO-IO combination (23.9 vs. 6.1 months, HR 0.37,p= 0.012). OS for TKI-IO treated patients was longer compared to TKI-monotherapy (HR 0.37, p = 0.050) at median follow-up of 24.1 versus 29.9 months. In a subanalysis of nivolumab treated patients, starting from second-line (n= 40), PFS was 5.5 months. The addition of nivolumab either in second-or later lines improved OS compared to repeated TKI- or mTOR-therapies alone (6.13 vs. 2.61 years, HR 0.46,p= 0.003).ConclusionBoth first-line IO-based combinations and nivolumab after first-line TKI-monotherapy prolong OS in a real-world setting.