On-Treatment Albumin-Bilirubin Grade: Predictor of Response and Outcome of Sorafenib-Regorafenib Sequential Therapy in Patients with Unresectable Hepatocellular Carcinoma

SIMPLE SUMMARY: Regorafenib after sorafenib therapy improved survival in patients with advanced hepatocellular carcinoma in the RESORCE study. The aim of our retrospective study was to investigate the predictors of response and outcome of regorafenib therapy in patients with unresectable hepatocellular carcinoma in whom sorafenib therapy had failed. We demonstrated that albumin-bilirubin grade at the initiation of regorafenib therapy is an independent predictor of disease control, progression-free survival, and overall survival. Patients with albumin-bilirubin grade 2 and an alpha-fetoprotein level of ≥20 ng/mL had the worst progression-free survival (after regorafenib therapy) and overall survival (after regorafenib and sorafenib therapy). Thus, a combination of albumin-bilirubin grade and alpha-fetoprotein level can be used to stratify patients with unresectable hepatocellular carcinoma by progression-free survival and overall survival probability for sorafenib–regorafenib sequential therapy. ABSTRACT: In the RESORCE study, regorafenib after sorafenib therapy improved survival in patients with advanced hepatocellular carcinoma (HCC). In total, 88 patients with unresectable HCC who received sorafenib–regorafenib sequential therapy were enrolled. The objective response rate and disease control rate were 19.3% and 48.9%, respectively, for regorafenib therapy (median duration: 8.1 months). Median progression-free survival (PFS) after regorafenib therapy was 4.2 months (95% CI: 3.2–5.1). The median overall survival (OS; from initiation of either sorafenib or regorafenib) was not reached in this cohort. According to multivariate Cox regression analyses, albumin-bilirubin (ALBI) grade at the initiation of regorafenib therapy is an independent predictor of disease control, PFS, and OS. Moreover, the combination of ALBI grade 2 and an alpha-fetoprotein (AFP) level of ≥20 ng/mL was an independent predictor of PFS (hazard ratio (HR): 3.088, 95% CI: 1.704–5.595; p < 0.001) for regorafenib therapy, and OS for both regorafenib (HR: 3.783, 95% CI: 1.316–10.88; p = 0.014) and sorafenib–regorafenib sequential (HR: 4.603, 95% CI: 1.386–15.29; p = 0.013) therapy. A combination of ALBI grade and AFP level can be used to stratify patients with unresectable HCC by PFS and OS probability for sorafenib–regorafenib sequential therapy.