First-line lenvatinib plus pembrolizumab versus sunitinib for advanced renal cell carcinoma: final overall survival analysis of CLEAR

The multinational phase 3 CLEAR trial randomized patients with previously untreated advanced renal cell carcinoma (aRCC) to lenvatinib plus pembrolizumab (LEN + PEMBRO) or sunitinib (SUN). The primary analysis, published in 2021, found better progression-free and overall with LEN + PEMBRO compared with SUN. The final overall survival analysis has now been published. At a median follow-up of 4 years, median overall survival was not reached in either arm, but was superior with LEN + PEMBRO, as was the median progression-free survival. Objective response rate was 71.3% with LEN + PEMBRO versus 36.7% with SUN (relative risk 1.94; 95% CI 1.67-2.26). Treatment-emergent adverse events occurred in more thant 90% of patients in both arms. The authors conclude that among patients with treatment-naïve aRCC, lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile.