First-Line Therapy for Advanced Renal Cell Carcinoma: Score-Matched Analysis of Dual Combination Immunotherapy versus Combination of Tyrosine Kinase Inhibitors and Immunotherapy in the TOURS Multicenter Study

Background: Standard first-line treatment for patients with advanced renal cell carcinoma (aRCC) has commonly included combined immune-oncology (IO) agents (IO-IO) or combinations of a tyrosine kinase inhibitor (TKI) and an IO agent (IO-TKI); however, there are few head-to-head comparative real-world studies, especially involving Japanese cohorts. Objective: To compare prognoses of patients treated with IO-IO or IO-TKI therapy in routine Japanese clinical practice. Methods: This retrospective study included 416 International Metastatic RCC Database Consortium (IMDC) intermediate- and poor-risk patients with aRCC treated with either IO-IO or IO-TKI at four institutions from September 2018 to February 2026. Effectiveness and safety outcomes were comprehensively compared. Overall (OS) and progression-free survival (PFS) rates were estimated with the Kaplan–Meier method. Results: We used propensity-score matching to compare 324 patients (IO-IO: 162; IO-TKI: 162). The IO-TKI cohort showed significantly higher objective response rates than the IO-IO cohort (66 versus 44%, respectively, p < 0.01), longer PFS (17.1 versus 8.4 months, respectively, HR = 0.56, p < 0.01), and longer OS (51.7 versus 31.5 months, respectively, HR = 0.70, p = 0.04), although OS did not reach significance in the IMDC risk-stratified subgroups. While all-grade adverse events (AEs) were more common in the IO-TKI group (94 versus 83%, respectively, p < 0.01), rates of immune-related AEs and corticosteroid administration were significantly higher in the IO-IO cohort. The study limitations include the retrospective design and treatment strategy solely decided by each physician. Conclusions: IO-TKI combinations were associated with higher rates of adverse events but survival benefits in IMDC intermediate- and poor-risk patients with aRCC.