Sorafenib for the Treatment of Advanced Renal Cell Carcinoma

Purpose: This report describes the U.S. Food and Drug Administration (FDA) review and approval of sorafenib (Nexavar, BAY43-9006), a new small-molecule, oral, multi-kinase inhibitor for the treatment of patients with advanced renal cell carcinoma (RCC). Experimental Design: After meeting with sponsors during development studies of sorafenib, the FDA reviewed the phase 3 protocol under the Special Protocol Assessment mechanism. Following new drug application submission, FDA independently analyzed the results of two studies in advanced RCC: a large, randomized, double-blinded, phase 3 international trial of single-agent sorafenib and a supportive phase 2 study. Results: In the phase 3 trial, 902 patients with advanced progressive RCC after one prior systemic therapy were randomized to 400 mg sorafenib twice daily plus best supportive care or to a matching placebo plus best supportive care. Primary study end points included overall survival and progression-free survival (PFS). A PFS analysis, pre-specified and conducted after a total of 342 events, showed statistically significant superiority for the sorafenib group (median = 167 days) compared with that for the controls (median = 84 days, log-rank P Conclusions: Sorafenib received FDA regular approval on December 20, 2005 for the treatment of advanced RCC based on the persuasive magnitude of improvement in PFS with acceptable safety. The recommended dose is 400 mg (two 200-mg tablets) twice daily taken either 1 h before or 2 h after meals. Adverse events were accommodated by temporary dose interruptions or reductions.