Comparative Evaluation of the Effectiveness of Nivolumab Versus Axitinib in the Second-Line Treatment of Patients with Metastatic Renal Cell Carcinoma: A Two-Center Experience

Objectives: This study aimed to compare the effectiveness of nivolumab and axitinib as second-line treatments in patients with metastatic renal cell carcinoma (mRCC) who had progressed after one prior tyrosine kinase inhibitor (TKI)-based therapy. Methods: We retrospectively evaluated 68 patients with mRCC who received nivolumab or axitinib as second-line treatment at two centers. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. Multivariable Cox proportional hazards regression models were performed to evaluate the association of treatment with PFS and OS after adjustment for International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group and year of second-line treatment initiation. Results: Nineteen patients received nivolumab, and 49 received axitinib. Median PFS was 9.27 months (95% confidence interval [CI], 5.75–12.79) with nivolumab and 5.87 months (95% CI, 4.73–7.01) with axitinib (log-rank p = 0.011). Median OS was 48.27 months (95% CI, 4.16–92.37) and 30.20 months (95% CI, 19.95–40.44), respectively (log-rank p = 0.027). In multivariable analysis, axitinib was associated with a significantly higher risk of progression or death compared with nivolumab (hazard ratio [HR], 3.494; 95% CI, 1.690–7.225; p = 0.001). IMDC risk group was also significantly associated with PFS (overall p = 0.003), whereas year of second-line treatment initiation was not (HR, 1.070; 95% CI, 0.883–1.296; p = 0.489). For OS, axitinib was associated with a significantly higher risk of death compared with nivolumab (HR, 2.410; 95% CI, 1.200–4.838; p = 0.013), while neither IMDC risk group (overall p = 0.477) nor treatment year (HR, 1.102; 95% CI, 0.922–1.317; p = 0.286) was significantly associated with OS. Conclusions: In this two-center retrospective cohort, nivolumab was associated with longer PFS and OS than axitinib in the second-line treatment of mRCC, and these associations remained significant after adjustment for IMDC risk group and year of treatment initiation. However, the retrospective design, small sample size, imbalance in treatment allocation and nephrectomy rates, and potential residual confounding limit causal interpretation. Prospective studies are warranted to confirm these findings.