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

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.