Effect of First-Line Combination Systemic Therapy on Favorable-Risk Clear Cell Renal Cell Carcinoma: A Retrospective...

Area of Science:

• Oncology
• Immunotherapy
• Nephrology

Background:

• Standard first-line therapy for advanced/metastatic clear cell renal cell carcinoma (RCC) involves immune checkpoint inhibitors (ICIs) and VEGFR-targeted tyrosine kinase inhibitors (TKIs).
• The precise clinical benefit of these combination regimens in patients with favorable International Metastatic Renal Cell Carcinoma Database Group (IMDC) risk remains incompletely understood.

Purpose of the Study:

• To retrospectively evaluate the efficacy of first-line systemic therapies in favorable-risk metastatic RCC patients.
• To compare progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) between TKI monotherapy and ICI-TKI combination regimens.

Main Methods:

• Retrospective analysis of 147 favorable-risk metastatic RCC patients treated between 2019-2023.
• Comparison of TKI monotherapy (n=110) versus ICI-TKI combinations (n=37).
• Evaluation of PFS, OS, and ORR using Kaplan-Meier and Cox regression analyses.

Main Results:

• Median PFS was 20.1 months overall; 26.2 months for ICI-TKI combinations vs. 17.0 months for TKI monotherapy (p=0.25).
• TKI monotherapy and liver metastasis were independent predictors of shorter PFS (HR 14.01, p=0.002 and HR 9.17, p<0.001, respectively).
• Objective response rate (ORR) was significantly higher with combination therapy (68% vs. 46%, p=0.01); 3-year OS rates were 89% (ICI-TKI) and 84% (TKI monotherapy).

Conclusions:

• Clinical heterogeneity impacts treatment outcomes even in favorable-risk metastatic RCC.
• Individualized therapy selection is crucial for optimizing outcomes in this patient population.
• Refined prognostic models are needed to better predict treatment response and guide clinical decisions.