Comparison of IO-IO and IO-TKI Treatment Outcomes in Metastatic Renal Cell Carcinoma: Influence of Metastatic Site...

The therapeutic efficacy of Immuno-Oncology combination therapy based on the number of metastatic organs in renal cancer has yet to be examined. Therefore, we herein compared the efficacy of dual immune checkpoint blockade (IO-IO) and combination of immunotherapy with tyrosine kinase inhibitors (IO-TKI) strategies in metastatic renal cell carcinoma (mRCC), with a focus on how the number of metastatic organs affects clinical outcomes.

This retrospective study included 147 patients with mRCC treated with systemic therapies between August 2015 and July 2023. A multivariable Cox proportional hazards model was used to examine the relationships between clinical parameters and survival. To examine whether the effects of the number of metastatic organs on survival varied between treatment regimens, interaction terms were evaluated.

In the multivariate Cox regression analysis, IMDC poor risk [hazard ratio (HR)=1.95; 95% confidence interval (CI)=1.19-3.18] and the presence of three or more metastatic organs in the IO-TKI group (HR=3.72; 95% CI=1.35-10.23) were identified as independent predictors of progression-free survival (PFS). In the IO-TKI group, patients with <3 metastatic organs had longer PFS than those with ≥3 metastatic organs. No significant difference in PFS was observed between <3 and ≥3 metastatic organs in the IO-IO group. This differential effect of the metastatic burden was confirmed by a significant interaction between the treatment group and number of metastatic organs (p for interaction=0.001).

The number of metastatic organs affects the efficacy of IO-TKI but has no effect on the efficacy of IO-IO treatment. We recommend considering the number of metastatic organs as an additional prognostic factor to optimize treatment selection for patients with mRCC.