Regorafenib in patients with unresectable hepatocellular carcinoma (uHCC) in routine clinical practice: Exploratory analysis of overall survival (OS) in the prospective, observational REFINE study.

433 Background: Regorafenib improved OS versus placebo in patients with uHCC who progressed on prior sorafenib in the RESORCE trial (Bruix J, 2017). An interim analysis of the observational REFINE study supported the safety and effectiveness of regorafenib in patients with uHCC in real-world clinical practice (Lim HY, 2021). Here we present an exploratory analysis of OS in REFINE by prior treatment. Methods: REFINE is a multicenter study that enrolled patients with uHCC for whom a decision to treat with regorafenib is made by the treating physician prior to enrollment according to the local health authority approved label. The primary objective of this study is safety, including the incidences of treatment-emergent adverse events (TEAEs) and dose modifications due to TEAEs (NCI-CTCAE v4.03). The secondary endpoints include OS, progression-free survival, and treatment duration. Results: Of the 1,031 patients enrolled, 1,008 were evaluable for interim analysis. At baseline, median age was 66 years (range 21–94); 62% of patients were Barcelona Clinic Liver Cancer stage C; 62% had Child–Pugh A disease; and 83% had an Eastern Cooperative Oncology Group performance status of 0 or 1. In total, 99% of patients received prior treatment: 96% had prior sorafenib, 9% had ≥1 prior immunotherapy (most common: nivolumab [50%] and pembrolizumab [21%]), and 6% had a multikinase inhibitor other than sorafenib (lenvatinib [62%]). The majority of patients experienced TEAEs (91%) and drug-related TEAEs (73%). Median OS was 12.9 months (95% confidence interval [CI] 11.4, 14.6). Subgroup analyses of OS by prior treatment are shown (Table). Conclusions: REFINE reflects the changing treatment landscape and supports the safety and effectiveness of regorafenib in real-world patients with uHCC who had prior systemic treatment other than sorafenib, including immunotherapy. This interim analysis suggests that patients who received regorafenib in the second line had longer OS than patients who received regorafenib in the third line and beyond. Clinical trial information: NCT03289273. [Table: see text]