Efficacy and safety of regorafenib alone or in combinations in the second-line setting for advanced hepatocellular carcinoma: A multicenter real-world study.

Abstract

e16172 Background: Due to drug resistance or intolerable adverse events, most hepatocellular carcinoma (HCC) patients tend to experience TKI-based first-line therapy failure. However, there is no unified choice of second-line treatment after this. Different authors have demonstrated that the combination of regorafenib and PD-1 inhibitors or TACE depicts synergistic effect. Therefore, the major goal of this research is to explore the efficacy and safety of regorafenib alone or in combinations as second-line therapy for advanced HCC in a real-world setting. Methods: In this study 94 advanced HCC patients (84 male and 10 females, average age of 59.8 years) were included from 3 Chinese centers between September 2018 and August 2022. It includes pathologically or clinically diagnosed advanced HCC patients who received regorafenib alone or in combinations in the second-line setting for at least 28 consecutive days. The primary endpoints were objective response rate (ORR, mRECIST criteria), and progression-free survival (PFS), however, the secondary endpoints included overall survival (OS) rate at 12-month, disease control rate (DCR) and treatment-related adverse events (TRAEs). Statistical analysis was performed with Kaplan-Meier method by using log-rank test. Results: 32 (34.0%) patients had BCLC stage B (others had BCLC stage C) and 72 (76.6%) patients were of Child-Pugh A (others were of Child-Pugh B). Half of the patients received regorafenib 160mg once daily during weeks 1–3 of each 4-week cycle. The proportions of patients received single drug regorafenib therapy (REGO) and combination therapies (COM) were 26.6% and 73.4%, respectively. The combination treatment regimens included regorafenib plus PD-1 inhibitors (36.2%), regorafenib combined with TACE (11.7%), and triple therapy (regorafenib, PD-1 inhibitors, TACE) (25.5%). The ORR and DCR were 28.7% and 72.3% with a median PFS of 8.4 months (range 6.33-10.47) and 12-month OS rate was 92.6%. The median PFS of COM group was 8.7 months ranging from 7.09-10.32, which was significantly longer compared to REGO group (4.2 months, range 0.45-7.95) (P = 0.031). Moreover, 66 (70.2%) recipients had TRAEs and most frequent TEAEs (≥5%) included hand-foot syndrome (31.9%), diarrhea (20.2%), rash (13.8%), fatigue (7.4%), oral mucositis (7.4%) and arthralgia (5.3%). 12 (12.8%) recipients had grade 3 TRAEs, including hand-foot syndrome (8.5%), hypertension (2.1%), diarrhea (1.1%) and rash (1.1%). No Grade 4 TRAE and new safety signal were identified. Conclusions: In the second-line treatment of advanced HCC, regorafenib alone or in combinations is effective and well-tolerated. The combination therapy showed a longer survival than regorafenib alone.