INTRODUCTION: Lenvatinib is an oral multikinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs) 1-3, fibroblast growth factor receptors (FGFRs) 1-4, platelet -derived growth factor receptor α (PDGFR-α), c-Kit, and RET. It has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. 

METHOD: Phase 3 trial was conducted, where patients with advanced renal cell carcinoma and no previous systemic therapy to receive Lenvatinib (plus pembrolizumab, Lenvatinib plus everolimus, or sunitinib were randomly assigned (in a 1:1:1 ratio) 

RESULTS: In this study 1069 patients were included who were randomly assigned to receive Lenvatinib plus pembrolizumab, Lenvatinib plus everolimus, or sunitinib. The results showed that progression-free survival was longer with Lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% Confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with Lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 955 CI, 0.53 to 0.80; P<0.0010. 

CONCLUSION: Based on the study findings, authors concluded that Lenvatinib plus pembrolizumab was related with considerably longer progression-free survival and overall survival than sunitinib. 

Reference: 

1. Motzer R, Alekseev B, Rha S-Y, et al.Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021; 384: 1289-1300.