Adjuvant Tyrosine Kinase Inhibitors in Treatment of Renal Cell Carcinoma: A Meta-Analysis of Available Clinical Trials.

Abstract

Although tyrosine kinase inhibitors (TKIs) are widely used in the metastatic setting, they have shown more limited effectiveness in the adjuvant setting. Despite multiple clinical trials, there has been no improvement in overall survival (OS) with the use of these agents as adjuvant therapy, and conflicting data on disease-free survival (DFS). We carried out a meta-analysis of available phase III randomized clinical trials on adjuvant TKIs in clear-cell renal cell carcinoma (RCC). Primary end points of our study were the effect of adjuvant TKIs on OS and DFS in the overall population. Furthermore, we investigated if use of adjuvant TKIs resulted in improved DFS among patients with different risk of tumor relapse. Higher-risk patients were patients with 1 or more of the following features: positive nodes (N+), T4 tumors and T3 tumors, with higher Fuhrman grades (3-4). We adopted Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to carry out our study. In the overall population, the pooled hazard ratio (HR) of OS and DFS was 0.89 (95% confidence interval [CI], 0.76-1.04) and 0.84 (95% CI, 0.76-0.93), respectively. In the low- and high-risk populations, the pooled DFS HR was 0.98 (95% CI, 0.82-1.17) and 0.85 (95% CI, 0.75-0.97), respectively. Adjuvant use of TKIs do not appear to provide a statistically significant OS benefit. However, a benefit in DFS has been observed in overall and high-risk populations, suggesting that better selection of patients might be important for the evaluation of adjuvant therapies in RCC.