Impact of First-Line Tyrosine Kinase Inhibitor Selection on Survival Outcomes With Second-Line Nivolumab in Metastatic Renal Cell Carcinoma

Abstract

IntroductionAccess to first-line immune checkpoint inhibitor (ICI) combinations in metastatic renal cell carcinoma (mRCC) remains limited in many low- and middle-income countries. Consequently, tyrosine kinase inhibitors (TKIs) are still widely used. This study investigates the impact of first-line sunitinib versus pazopanib on survival outcomes with second-line nivolumab.MethodsWe conducted a retrospective analysis of 245 patients with mRCC from the Turkish Oncology Group Kidney Cancer Consortium Database. Patients received first-line sunitinib or pazopanib, followed by second-line nivolumab. Primary endpoints were time to treatment failure (TTF) and overall survival (OS). Subgroup analyses were performed based on IMDC risk classification and presence of sarcomatoid features.ResultsA total of 245 patients who were treated with sunitinib or pazopanib monotherapy as first-line treatment followed by nivolumab as second-line treatment were included in this study. Median TTF following nivolumab initiation was similar between prior sunitinib and pazopanib groups (7.79 vs 7.72 months; p = 0.892). Median OS-2 was 27.21 months with prior sunitinib and 18.92 months with prior pazopanib (p = 0.496). In patients with sarcomatoid features (n = 20), those pretreated with pazopanib demonstrated numerically longer OS-2 compared to sunitinib (p = 0.023), although the small sample size limits definitive conclusions.ConclusionNo significant differences in survival outcomes were observed between first-line sunitinib and pazopanib before nivolumab in mRCC. In the small subgroup with sarcomatoid features, pazopanib pre-treatment was associated with a numerically longer survival. These findings warrant cautious interpretation and further prospective validation, especially in resource-constrained settings.