Efficacy and Safety of Regorafenib with or without PD-1 Inhibitors as Second-Line Therapy for Advanced Hepatocellular Carcinoma in Real-World Clinical Practice

BACKGROUND: Regorafenib is the first oral targeted drug as a second-line agent in patients with advanced hepatocellular carcinoma (HCC) who progressed on sorafenib treatment. Recently, several studies demonstrated that the combination of regorafenib and PD-1 inhibitors showed a synergistic effect. Our study aimed to evaluate the efficacy of regorafenib with PD-1 inhibitors (RP) and regorafenib alone (R) as second-line treatment for advanced HCC. METHODS: From October 2018 to January 2022, our retrospective study evaluated advanced HCC patients who received regorafenib with PD-1 inhibitors or regorafenib alone as a second-line treatment at the Second Affiliated Hospital of Nanchang University, China. The efficacy and safety were compared between RP and R groups. RESULTS: In total, 78 patients were enrolled in our study and were separated into two groups – RP group (48) and R group (30) – according to the criteria. The ORR of RP group and R group was 18.8% and 10%, respectively, and the DCR was 66.7% and 43.3%, respectively. The RP group had a longer mPFS (5.9 months vs 3.0 months, P<0.001) and mOS (12.9 months vs 10.3 months, P=0.010) than the R group. Regorafenib monotherapy is an independent prognostic factor for OS and PFS. In OS, subgroup analysis showed that patients with AFP ≥ 400ng/mL, BCLC C stage and extrahepatic metastasis may benefit from RP, while in PFS, subgroup analysis showed that patients with BCLC C stage, AFP ≥ 400ng/mL, extrahepatic metastasis, ALBI ≥-2.60 and first-line treatment of sorafenib may benefit from RP. The incidence of grade 3/4 adverse reaction in the two groups was 22.9% and 23.3%, respectively, with no significant statistically difference (P=0.966). CONCLUSION: In the second-line therapy of advanced HCC, compared to regorafenib alone, the combination of regorafenib and PD-1 inhibitors showed promising efficacy and tolerable drug toxicity.