Efficacy and Safety of TACE Combined with Regorafenib Plus PD-1 Inhibitor in the Treatment of Hepatocellular Carcinoma After Sorafenib Resistance

PURPOSE: To evaluate the efficacy and safety of TACE combined with regorafenib plus PD-1 inhibitor as a second-line therapy for hepatocellular carcinoma after sorafenib resistance. MATERIALS AND METHODS: The clinical data of 76 patients with hepatocellular carcinoma who were drug-resistant to sorafenib from September 2018 to May 2022 in the tumor intervention department were collected. Among them, 35 patients used TACE combined with regorafenib plus PD-1 inhibitor (TACE-R-P) as second-line treatment, and the remaining 41 patients used TACE combined with regorafenib (TACE-R) as second-line treatment. The mRECIST (modified Response Evaluation Criteria in Solid Tumors) standard was used to evaluate the therapeutic effect. The progression-free survival (PFS) and overall survival (OS) of the two groups were compared. Blood samples were collected before and after treatment to detect the changes in biochemical indicators, and the adverse events (AEs) related to treatment were recorded. RESULTS: A total of 76 patients were included in the study, including 35 patients receiving TACE-R-P treatment and 41 patients receiving TACE-R treatment. Patients in the TACE-R-P group had longer median OS (19.7months vs 15.2months, HR:0.7716, 95% CI:0.4767–1.2490, P=0.03), longer median PFS (6.3months vs 3.8months, HR:0.6032, 95% CI:0.3727–0.9763, P=0.0029), higher objective response rate (37.14% vs 19.51%, P=0.001) and higher disease control rate (71.43% vs 48.78%, P=0.001) than those in the TACE-R group. Multivariate analysis showed that Child–Pugh grade (B/A; HR=1.283, 95% CI: 0.623–1.707, P=0.014), PVTT (Yes/No, HR=1.455, 95% CI: 0.977–2.038, P=0.018), extrahepatic metastasis (Yes/No, HR=1.766, 95% CI: 1.135–2.302, P=0.022) and treatment option (TACE-R/TACE-R-P, HR=1.930, 95% CI: 1.461–2.850, P=0.017) were independent prognostic factors for OS. There was no significant difference in the incidence and severity of AEs between the two groups. CONCLUSION: TACE-R-P treatment can be more effective than TACE-R treatment for HCC after sorafenib resistance and can be given priority as a second-line treatment for HCC.