lenvatinib + letrozole

Lenvatinib is a small molecule, oral multikinase inhibitor that targets several receptor tyrosine kinases involved in tumor proliferation and angiogenesis, including vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial growth factor receptor 3 (VEGFR3), fibroblast growth factor receptor 1 (FGFR1), fibroblast growth factor receptor 2 (FGFR2), fibroblast growth factor receptor 3 (FGFR3), platelet-derived growth factor receptor alpha (PDGFRα), KIT, and RET. It is primarily used for the treatment of thyroid cancer, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and endometrial cancer[1][2][6][8]. Letrozole is a nonsteroidal aromatase inhibitor that reduces estrogen production by inhibiting the aromatase enzyme; it is mainly indicated for hormone receptor-positive breast cancer in postmenopausal women[3]. The combination of lenvatinib plus letrozole has been investigated in clinical trials for advanced estrogen receptor-positive/HER2-negative metastatic breast cancer. This combination leverages lenvatinib’s inhibition of RET—a gene regulated by estrogen signaling—and letrozole’s suppression of estrogen synthesis to target cross-talk between these pathways. Early-phase studies have shown manageable toxicity and preliminary antitumor activity with this regimen[4].