Sequential therapy including regorafenib for unresectable hepatocellular carcinoma: Effect of early relative changes in hepatic functional reserve after regorafenib administration on prognosis.

Aim Regorafenib is a second-line treatment for unresectable hepatocellular carcinoma (u-HCC) after sorafenib-refractory treatment. This study examined the effects of regorafenib administration on hepatic functional reserve and the treatment course after regorafenib discontinuation. Methods This retrospective, multicenter study involved 51 patients treated with regorafenib after sorafenib-refractory treatment for u-HCC at seven institutions before March 2021. Results Fourteen, 13, and 24 patients were classified based on modified albumin-bilirubin (mALBI) grade 1, 2a, and 2b, respectively. The median survival time (MST) and progression-free survival were 16.7 and 3.3 months, respectively. Only mALBI grade 2b or 3 was significantly associated with survival rate (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.01-4.49; p=0.047). A comparison of median ALBI scores at the initiation of regorafenib (-2.35) with those at 4 weeks (-1.93) revealed a significant relative change (p=0.0001). After 4 weeks, grade 1 or 2a persisted in 15 patients (Group 1); grade 1 or 2a deteriorated to 2b in 12 patients (Group 2); grade 2b or 3 before regorafenib administration was present in 22 patients (Group 3); and MST was 33.3, 12.8, and 11.3 months in the three groups, respectively (p=0.05). Patients treated with lenvatinib (LEN) (n=27, MST=23.4 months) after regorafenib had a significantly longer survival time from regorafenib initiation than those not treated with LEN (n=24, 11.8 months; p=0.043). Conclusions Hepatic functional reserve significantly declined after regorafenib administration. During regorafenib treatment, favorable hepatic functional reserve before administration and maintenance of favorable hepatic reserve after administration lead to prolonged prognosis. This article is protected by copyright. All rights reserved.