Chemotherapy: Open Access
Open Access

Abstract

The Newest Targeted Therapeutics for Thyroid Cancer: Development of Sorafenib and Lenvatinib

Mark Steven Cohen

Sorafenib was specifically developed using high-throughput screening and structure-activity relationships to target important pathogenic pathways in thyroid cancer. Initially developed to target rapidly accelerated fibrosarcoma (RAF) kinase, it was also found to inhibit several key receptor tyrosine kinases (RTKs) within the mitogen-activated protein kinase (MAPK) pathway. Preclinical and clinical studies demonstrated significant efficacy in differentiated thyroid cancer (DTC), and following the phase III DECISION trial comparing sorafenib to placebo in DTC, it received Food and Drug Administration (FDA) approval in November 2013 for treatment of advanced, radioactive iodine-refractory DTC. Sorafenib is shown to significantly improve progression free survival (PFS) an average of 10.8 months (hazard ratio [HR] 0.59, 95% CI, 0.45-0.76; P