Site of metastasis and clinical outcomes in patients with advanced renal cell carcinoma treated with TKI monotherapy or combination therapy: A real-world analysis.

e16513 Background: Tyrosine kinase inhibitors (TKIs), either in monotherapy or in combination with immunotherapeutic agents (IO), have become the standard of care for the first-line treatment of advanced or metastatic renal cell carcinoma (RCC). Common sites of metastasis in RCC include the lymph nodes, lungs, liver, pancreas, bones, and brain. This study aims to analyze the clinical outcomes of patients treated with TKI monotherapy and TKI-IO combination therapy based on the site of metastasis. Methods: A retrospective analysis was conducted on the clinical characteristics and outcomes of RCC patients treated with first-line TKI and TKI-IO in Spanish and Italian institutions. The study employed a descriptive analysis, calculating the median follow-up using the reverse Kaplan-Meier method. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional-hazard models were utilized to determine hazard ratios (HRs) with a 95% confidence interval. Results: Out of 369 eligible patients, 285 received TKI monotherapy, and 84 were treated with TKI-IO. The median follow-up was 84.34 months (95% CI; 73.82 - 101.91) in the TKI group and 17.58 months (95% CI; 13.11 - 45.77) in the TKI-IO group. PFS was significantly longer with TKI-IO compared to TKI in patients with lung metastasis (48.79 months vs. 21.95 months) (HR 0.59 0.39;0.91; p=0.02). While PFS was longer in patients with bone metastasis (41.3 months vs. 19.09 months) (HR 0.56 0.28 ; 1.13; p=0.11), liver metastasis (41.3 months vs. 15.97 months) (HR 0.52 0.25 ; 1.06; p=0.07), and lymph node metastasis (32.82 months vs. 20.14 months) (HR 0.67 0.43 ; 1.04; p=0.08) with TKI-IO, these differences were not statistically significant. TKI monotherapy showed longer PFS in patients with pancreatic metastasis (41.64 months vs. 22.7 months) (HR 1.37 0.5 ; 3.72; p= 0.54). OS was numerically longer in TKI-IO-treated patients across various subgroups but did not reach statistical significance. Notably, OS was significantly higher in patients with pancreatic metastasis compared to those with other metastatic locations (139 months vs. 42.74 months) (HR 0.350.18;0.69; p<0.01). Conclusions: Our study underscore the superiority of TKI-IO combination therapy over TKI monotherapy, revealing consistently favourable outcomes across various metastatic sites. Notably, an intriguing exception emerged in the context of pancreatic metastasis, where patients exhibited an extended PFS with TKI monotherapy. The implications of our data suggest a tailored approach for this specific subset, wherein frontline immunotherapy may not be the optimal choice.