REAL-WORLD OUTCOMES OF SECOND- AND THIRD-LINE THERAPIES AFTER FIRST-LINE VEGFR-TKI FAILURE IN METASTATIC RENAL CELL CARCINOMA: A SINGLE-CENTER EXPERIENCE FROM TÜRKİYE

Objective: Immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) have transformed the treatment of metastatic renal cell carcinoma (mRCC), yet access limitations continue to shape real-world practice. This study evaluated the outcomes of second- and third-line systemic therapies administered after TKI failure within a single-center cohort.Materials and methods: This retrospective study included 50 patients with histologically confirmed mRCC treated between 2014 and 2024. Eligible patients had received at least one line of TKI therapy and subsequently received second-line nivolumab or axitinib. Survival outcomes were analyzed using Kaplan – Meier and log-rank tests.Results: The median age was 63 years; 76% were International Metastatic RCC Database Consortium intermediate-risk, and 82% had undergone nephrectomy. First-line therapy consisted of sunitinib (72%) or pazopanib (28%), with a median progression-free survival (PFS) of 7 months. In the second line, 40 patients (80%) received nivolumab and 10 (20%) axitinib. Median PFS and OS were 10 and 20 months for nivolumab vs. 4 and 5 months for axitinib (both p<0.001). Three patients remained on nivolumab at the data cutoff. Among 36 patients receiving third-line therapy, axitinib and cabozantinib were the most commonly used agents. Median PFS was 5.0 months with axitinib and 5.5 months with cabozantinib, while median OS was 7.0 months in both groups (p>0.05). Five patients (four axitinib and one cabozantinib) were alive at the last follow-up.Conclusion: In this cohort, nivolumab was associated with longer PFS and OS compared to axitinib in the second-line setting after TKI failure, whereas axitinib and cabozantinib demonstrated similar outcomes in the third-line setting.