Impact of Estimated Glomerular Filtration Rate and Serum C-Reactive Protein Level to Overall Survival After Second-Line Targeted Therapy Following Immuno-Oncology Combination Therapy for Advanced Renal Cell Carcinoma

Objectives: Immune checkpoint inhibitor (ICI)-based combination therapies are first-line treatments for locally advanced or metastatic renal cell carcinoma (mRCC). However, second-line treatment efficacy remains uncertain due to limited large randomized trials. This study evaluated real-world oncological outcomes after second-line treatments in patients who received combination ICIs as first-line treatment. Methods: Among 467 patients who received ICI combination therapy as first-line treatment for mRCC between January 2018 and January 2024, those who received cabozantinib (Cabo) or axitinib (Axi) as second-line treatment were included in this study. The patient characteristics at the initiation of second-line treatment, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Prognostic factors associated with OS after the initiation of second-line treatment were evaluated. Results: The Cabo and Axi groups included 87 and 45 patients, respectively. Median OS and PFS after the initiation of secondary treatment were 32 and 9 months in the Cabo group (p = 0.269), and 33 and 12 months in the Axi group (p = 0.399). Multivariable analysis identified serum C-reactive protein (CRP) ≥ 0.6 mg/dL and estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m² at the start of secondary treatment as independent predictors of OS. Stratification by these factors revealed a significant OS difference (p < 0.001). Conclusions: Oncological outcomes after the initiation of secondary treatment did not differ significantly between the Cabo and Axi groups. An eGFR < 40 mL/min/1.73 m² and CRP ≥ 0.6 mg/dL at the start of Cabo or Axi treatment were independent OS predictors after secondary treatment.