Impact of first-line tyrosine kinase inhibitor selection on survival outcomes with second-line nivolumab in metastatic renal cell carcinoma.

Introduction: Access 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.

Methods: We 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.

Results: A 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.

Conclusion: No 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.