Tolerability and Effectiveness of Regorafenib Treatment in Patients with Unresectable Hepatocellular Carcinoma: Real-World Data from the United States.

Introduction: While several systemic therapies are available for unresectable hepatocellular carcinoma (uHCC), there is a lack of granular real-world evidence to support the efficacy and safety of these therapies. The REFINE study evaluated safety and effectiveness of regorafenib in a global population under real-world practice conditions. This sub-analysis describes the safety and effectiveness of regorafenib among the United States (US) subset of patients in the REFINE study relative to patients in the non-US subset.

Materials and methods: REFINE was an international, prospective, multicenter observational study. Eligible patients were those with uHCC for whom a decision to treat with regorafenib had already been made. The primary study endpoint was the frequency of documented treatment-emergent adverse events (TEAEs). Additional endpoints included overall survival and progression-free survival. Groups were compared descriptively.

Results: Of 1005 patients, 65 were from the US and 940 were from other countries. 91% of patients in the US subset (n=59) and 92% in the non-US subset (n=862) experienced ≥1 TEAE. Common adverse events (AEs) included gastrointestinal disorders, fatigue, and hand-foot skin reaction. Median overall survival for patients in the US subset was 11.4 months (interquartile range [IQR]: 4.7-25.4) and 13.2 months (IQR: 5.8-26.3) in the non-US subset. Median progression-free survival was 3.4 months (IQR: 2.4-6.1) for patients in the US subset and 3.9 months (IQR: 2.2-8.5) in the non-US subset.

Conclusion: Regorafenib was associated with similar safety and effectiveness outcomes for patients in the US and non-US subsets of the REFINE study. Differences in the incidence of certain AEs may be due to differences in treatment management between study sites or baseline disease status. These findings are consistent with the phase 3 RESORCE trial and corroborate the safety and effectiveness of regorafenib as a subsequent-line treatment in US patients with uHCC.