Efficacy and Safety of Lenvatinib in Combination With Other Tyrosine Kinase Inhibitors for Metastatic Renal Cell Carcinoma

Objective: This meta-analysis evaluates the efficacy and safety of lenvatinib, both as monotherapy and in combination with other (tyrosine kinase inhibitors) TKIs, compared with other TKIs in metastatic renal cell carcinoma (RCC) treatment. Methods: We searched for relevant studies from inception to February 2024 using PubMed, Web of Science, Cochrane Library, and Scopus. Eligible studies reported on the efficacy and safety of lenvatinib alone or in combination with other TKIs versus other TKIs for metastatic RCC. Primary outcomes included progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR), adverse events (AEs), and health-related quality of life (HRQOL). Results: Seventeen studies met the inclusion criteria. Lenvatinib, especially in combination therapies, significantly improved PFS (HR: 0.46, 95% CI: 0.38-0.54, P <0.001) and OS (HR: 0.80, 95% CI: 0.70-0.91, P <0.001) compared with other TKIs. Quality of life analyses showed mixed results, with EQ-5D demonstrating significant improvement (HR: 1.21, 95% CI: 0.90-1.53, P <0.001), while EORTC QLQ-C30 was not statistically significant. ORR analysis indicated a higher likelihood of achieving a complete or partial response with lenvatinib (OR: 2.04, 95% CI: 1.15-2.93, P =0.00). The analysis of total AEs above grade 3 showed no significant difference between lenvatinib and other TKIs (OR: -0.08, 95% CI: -0.21 to 0.06, P =0.26). Conclusions: Lenvatinib significantly enhances survival outcomes in metastatic RCC patients compared with other TKIs. While associated with various adverse events, its safety profile is comparable to other TKIs.