Retrospective head-to-head comparison of first-line TKI and ICI treatment strategies in advanced renal cell carcinoma

The current standard of care for locally advanced or metastatic renal cell carcinoma (aRCC) is either a combination of two immune checkpoint inhibitors (ICI) or an ICI plus a tyrosine kinase inhibitor (TKI). These two options have not been compared head-to-head. The German research platform CARAT estimated the real-world effectiveness of these combinations by emulating a hypothetical randomized trial of aRCC patients from a prospective, observational clinical registry. Inverse probability of treatment weighting was used to compare first-line ICI + TKI (n=447), ICI + ICI (n=257), and TKI monotherapy (n=166). IPTW-adjusted median real-world PFS and OS were 12.3 and 29.0 months for TKI + ICI, 8.3 and 21.9 months for ICI + ICI, and 8.5 and 31.7 months for TKI monotherapy. Compared to ICI + TKI, survival tended to be worse for ICI + ICI (rwPFS: HR 1.25; 95% CI 1.00-1.58; OS: HR 1.25; 0.95-1.63). Median time-to-deterioration of health-realted quality of life did not differ substantially between the strategies. The authors conclude that there was a trend toward superior survival with first-line ICI + TKI compared with ICI + ICI. TKI monotherapy may remain a viable first-line option in selected patients who cannot tolerate immunotherapy (visual abstract).