Real-world dosing of regorafenib in patients with unresectable hepatocellular carcinoma (uHCC): Final analysis of the prospective, observational REFINE study.

518 Background: Final results from the real-world REFINE study confirmed the safety and effectiveness of regorafenib (REG) in a broad population of patients (pts) with uHCC that was consistent with the results from RESORCE, in which REG prolonged overall survival (OS) vs placebo in pts with uHCC who progressed on prior sorafenib. Here we evaluate baseline characteristics and outcomes according to the initial REG dose. Methods: REFINE (NCT03289273), an international, prospective, multicenter study, enrolled pts with uHCC for whom a decision to treat with REG was made by the treating physician prior to enrollment according to the local health authority approved label (160 mg/day, 3 weeks on/1 week off). The primary objective was safety (NCI-CTCAE v4.03); secondary endpoints included OS and progression-free survival (PFS). Results: Of 1005 pts eligible for analysis, 47%, 11%, 40%, and 3% initiated REG at 160 mg, 120 mg, 80 mg, and 40 mg, respectively. A higher proportion of pts from Asia initiated REG at 160 mg (51%) vs non-Asian countries (42%), and 67% were Child–Pugh A in Asia vs 54% in non-Asian countries at study entry. Pts initiating REG at 160 mg were more likely to be Child–Pugh A and albumin–bilirubin (ALBI) grade 1 vs pts initiating REG at <160 mg (Table). A higher proportion of pts (53%) who initiated REG at 160 mg ended prior sorafenib at 800 mg/day. Of the pts intolerant to prior sorafenib (n=91), more pts started REG at 80 mg (49%), followed by 160 mg (32%) and 120 mg (9%). Median duration of REG treatment was similar across initial dose levels (overall 3.7 months). Any-grade TEAEs were reported for 90%, 93%, and 93% of pts initiating REG at 160 mg, 120 mg, and 80 mg, respectively. TEAEs led to dose modifications in 49%, 51%, and 38% and to dose reductions in 34%, 26%, and 17% of pts. Median OS was 15.8 months in pts who initiated REG at 160 mg, 13.3 months at 120 mg, and 11.1 months at 80 mg. Median PFS was similar across doses (overall 3.9 months). Conclusions: In this real-world study, most pts with uHCC initiated REG at 160 mg or 80 mg/day. A higher proportion of pts from Asia initiated REG at the recommended dose, and a higher proportion of pts initiating REG at 160 mg had relatively better liver function at study entry. Safety was generally similar regardless of initial dose, and OS was observed to be longer in pts initiating REG at 160 mg vs lower doses. Clinical trial information: NCT03289273 . [Table: see text]