Regorafenib for Hepatocellular Carcinoma in Real-World Practice (REFINE): A Prospective, Observational Study

Abstract

Introduction: In the phase 3 RESORCE trial, regorafenib prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC) whose disease progressed on prior sorafenib. The prospective, observational REFINE study aimed to evaluate the safety and effectiveness of regorafenib in a broader population of patients in real-world clinical practice, including patients with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, Child-Pugh B liver status, and sorafenib intolerance.

Methods: This international, prospective, multicenter study (NCT03289273) enrolled patients with uHCC for whom the decision to treat with regorafenib was made by their physician before enrollment, according to the local health authority-approved label. The primary aim was to evaluate the safety of regorafenib, including the incidence of treatment-emergent adverse events (TEAEs) and dose modifications due to TEAEs.

Results: Of the 1,028 patients enrolled, 1,005 initiated regorafenib and were eligible for analysis. Median age was 66 years (range 21-94); most patients were male (83%), Child-Pugh A (61%), and had an ECOG PS of 0 or 1 (82%) at study entry. Overall, 47%, 11%, and 40% of patients initiated regorafenib at 160, 120, and 80 mg/day, respectively. Median treatment duration was 3.7 months (range 1 day to 38.9 months). Dose modifications and permanent discontinuation of regorafenib due to TEAEs occurred in 45% and 31% of patients, respectively. The most common drug-related TEAEs were hand-foot skin reaction (31%), diarrhea (26%), and fatigue (15%). Median OS was 13.2 months (95% confidence interval 11.6, 14.8).

Conclusion: The results of the real-world REFINE study confirmed the safety and effectiveness of regorafenib in a broad population of patients with uHCC. Of patients who received standard regorafenib dosing in REFINE, safety and efficacy findings were consistent with those reported in the RESORCE trial.

Keywords: Hepatocellular carcinoma; Observational study; Prospective; Real-world evidence; Regorafenib.

Fig. 1.

The incidence and severity of TEAEs in sorafenib-intolerant patients in REFINE versus the phase 3 RESORCE population. Incidence (bubble size): Percentage of patients with TEAE in the respective group. Severity (color): Percentage of patients with serious TEAE in the respective group. HFSR, hand-foot skin reaction; TEAE, treatment-emergent adverse event.

Fig. 2.

Overall survival. CI, confidence interval; OS, overall survival.

Fig. 3.

Overall survival stratified by regorafenib treatment line (a), geographic region (Asia vs. non-Asia; b), geographic region (Asia vs. non-Asia) in patients with Child-Pugh A (c), baseline Child-Pugh classification (d), baseline ALBI grade (e), and sorafenib intolerance (f). ALBI, albumin-bilirubin; CI, confidence interval; OS, overall survival. ^aData are not shown for regorafenib in the first-line setting due to small sample size. Logrank p value was computed across all treatment lines. ^bData are not shown for Child-Pugh C disease and “not evaluable” due to small sample size. Logrank p value was computed across all Child-Pugh classification.