Regulatory Decision Summary for Stivarga

The approval was based on a pivotal randomized placebo-controlled Study 15982 (RESORCE) in 573 patients with hepatocellular carcinoma (HCC). The primary efficacy endpoint median overall survival (OS) was statistically significantly improved in patients treated with regorafenib (10.6 months) compared to placebo (7.8 months). The results also showed statistically significant improvement in the secondary endpoints of progression-free survival and time to progression.

The most frequent treatment emergent adverse events (TEAEs) during regorafenib treatment in the RESORCE trial included hand-foot skin reaction (HFSR) - 51%, diarrhea (41%), infection (31%), decreased appetite (31%), hypertension (31%) and fatigue (29%). Based on trial safety data pancreatitis was added to the adverse event (AE) list and fatal outcome was added in association with the already listed AE infection.

Given the underlying disease in HCC patients, hepatic failure/injury and elevations in Aspartate transaminase (AST), Alanine transaminase (ALT), and bilirubin events were more common than in the colorectal cancer (CRC) and gastrointestinal stromal tumors (GIST) trials. However, the incidence of hepatic failure on the regorafenib arm was not higher when compared to the placebo group. Given that no data are available for patients with severe hepatic impairment, regorafenib is not recommended in this population of patients. No dose adjustment is required in patients with mild or moderate hepatic impairment.

Regorafenib in the second-line HCC treatment has a manageable safety profile if administered according to the recommended dose and dosing regimen, and with proper monitoring as per recommendations outlined in the Product Monograph.

The Benefit/Risk profile of Stivarga (regorafenib) in the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib is considered favorable.