Long-Term Safety and Tolerability of Sorafenib in Patients with Advanced Non–Small-Cell Lung Cancer: A Case-Based Review

Abstract Background Sorafenib, a small-molecule inhibitor of multiple kinases involved in tumor growth and progression, is approved for the treatment of advanced renal-cell carcinoma and advanced hepatocellular carcinoma. Encouraging activity and good tolerability of daily oral sorafenib, either as a single agent or in combination with gefitinib, have been demonstrated in phase I-II trials in patients with advanced non–small-cell lung cancer (NSCLC). Currently, minimal data are available describing the long-term safety and tolerability of sorafenib in patients with NSCLC. Materials and Methods We describe a series of 12 patients with advanced NSCLC (derived from 1 phase I and 2 phase II trials) who achieved long-term (ie, > 12 months) disease control and continued to receive sorafenib alone or in combination with gefitinib beyond the end of the study in which they were enrolled. Results The safety profile of sorafenib administered on a long-term basis did not differ significantly from that seen previously in the shorter term. The majority of adverse events (AEs) were Grade 1-2 in severity. Five of the 12 patients experienced no ≥ Grade 3 AEs. There was no evidence of increased frequency or severity of AEs over time, or of late AEs, and no patient in this series discontinued study treatment because of AEs. Conclusion In patients with advanced NSCLC who achieve a prolonged response or stable disease with sorafenib given as a single agent or as part of a combination regimen, sorafenib treatment could be continued until disease progression without major long-term safety or tolerability problems.