First-line TKI vs IO for Metastatic Renal Cell Carcinoma: IMDC Score Stratified Retrospective Analysis
We evaluate the outcomes of patients with primary metastatic renal cell carcinoma treated with upfront nephrectomy followed by pazopanib, sunitinib, or ipilimumab-nivolumab as first-line therapy. We used a large multinational federated network database to identify 1,956 predominantly elderly Caucasian male patients from January 1, 2010, to January 1, 2024, who were diagnosed with metastatic renal cell carcinoma and received first-line systemic therapies with pazopanib, sunitinib, or ipilimumab-nivolumab. Overall survival was evaluated using the mortality rates, Kaplan-Meier curves, and multivariable analysis. We observed decreasing median survival with increasing International Metastatic Renal Cell Carcinoma Database (IMDC) score. Patients receiving ipilimumab-nivolumab demonstrated the lowest mortality rate, followed by sunitinib and pazopanib. Notably, pazopanib had a significantly higher risk of death compared to ipilimumab-nivolumab in low-risk mRCC (IMDC 0 and 1-2) with higher hazard ratio and significant log-rank testing in patients with IMDC score of 0. No significant difference in overall survival was observed between pazopanib and sunitinib for all IMDC risk cohorts. These findings suggest potential advantages for ipilimumab-nivolumab as first-line therapy in favorable-risk mRCC. Our results agree with previous studies, support guidelines, stratify differences in overall survival by IMDC score, and provide direct evidence comparing pazopanib to ipilimumab-nivolumab. These results may provide guidance for clinical decision-making in patients based on IMDC score, drug affordability, and tolerability.
Keywords: mRCC (Metastatic Renal Cell Carcinoma), TKI (tyrosine kinase inhibitor), immunomodulator (IO), ipilimumab-nivolumab, IMDC (International Metastatic renal cell Carcinoma Database Consortium)
