Regorafenib use in patients with unresectable hepatocellular carcinoma: analyses of subgroups of special interest in the observational REFINE study

Background: The findings of the prospective, real-world REFINE trial supported the safety and efficacy of regorafenib reported in the phase III RESORCE study, in a broader population of patients with unresectable hepatocellular carcinoma (HCC). This post hoc analysis evaluated patient subgroups based on liver function, liver cancer stage, and prior treatment. Patients and methods: Patients were analyzed by subgroups based on liver function [Child–Pugh (CP)–B/B7], prior treatment [prior orthotopic liver transplant (pOLT), transarterial chemoembolization (TACE)/transarterial radioembolization (TARE)], and Barcelona Clinic Liver Cancer (BCLC) stage. The primary objective was to evaluate the safety of regorafenib. Secondary objectives included effectiveness endpoints of overall survival (OS) and duration of treatment. All analyses were descriptive with no adjustment for confounders. Results: A total of 1005 patients were evaluable (overall population). In patients with CP–B (n = 123) compared with the overall population, the incidence of grade ≥3 (28% versus 27%) and serious drug-related treatment-emergent adverse events (TEAEs) was similar (11% versus 9%), whereas TEAEs leading to permanent discontinuation of regorafenib were more common (28% versus 16%). In patients with prior TACE (n = 584), the incidence of TEAEs was generally similar to patients without prior TACE (n = 421) and the overall population (92%, 91%, and 92%, respectively). Median OS was 12.3-19.3 months across all subgroups except CP–B/B7 (6.4/6.7 months). Conclusions: This subgroup analysis of REFINE provides further evidence on the safety and effectiveness of regorafenib demonstrated in RESORCE, in underrepresented subgroups (CP–B, BCLC stage B/C, pOLT) and in those previously treated with TACE/TARE.