Efficacy and safety of transcatheter arterial embolization combined with ablation and regorafenib for unresectable hepatocellular carcinoma patients failing first-line treatment: a real-world study.

Background: Most patients with hepatocellular carcinoma (HCC) have progressed to the intermediate or advanced stage when diagnosed and are ineligible for curative therapies. The currently available therapeutic options, including ablation, radioembolization, transarterial chemoembolization (TACE), and systemic treatment with tyrosine kinase inhibitors (TKIs), provide limited survival benefits. Studies have suggested that the combination treatment may provide better therapeutic outcomes as compared to individual treatments. However, studies of regorafenib in combination with local treatment in patients after failure of first-line treatment are still lacking, and the efficacy of this regimen has not been thoroughly investigated. Therefore, the purpose of our study was to determine the efficacy and safety of TACE combined with regorafenib as second-line therapy in patients with unresectable HCC.

Methods: Patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stage B or C who received the combined treatment of TACE, ablation, and regorafenib or regorafenib plus anti-PD-1 immune checkpoint inhibitors (ICIs) in Beijing You'an Hospital between April 2020 to June 2023 were reviewed. The primary endpoint was overall survival (OS), while progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were the secondary endpoints.

Results: A total of 73 patients were enrolled in our study, including 63 (86.3%) males and 10 (13.7%) females. Among these patients, 16 (21.9%) had portal vein tumor thrombosis (PVTT), and 33 (45.2%) had extrahepatic metastasis. There were 53 (72.6%) patients with multiple tumors and 23 (31.5%) with large tumors (>30 mm). All patients received TACE combined with regorafenib, while 37 (50.7%) additionally received ICIs and 36 (49.3%) did not. The majority (n=61, 83.6%) of patients in our cohort received ablation therapy. There were 22 (30.1%) patients with an alpha fetoprotein (AFP) level >400 U/L. The average follow-up of the cohort was 24.6 months, the median PFS was 7.06 months [95% confidence interval (CI): 4.77-9.36 months], and the median OS was 24.0 months (95% CI: 6.25-41.75 months). According to the modified Response Evaluation Criteria in Solid Tumors, the ORR was 58.9%, and the DCR was 91.8%. No adverse events (AEs) were reported in the 11 patients in the study. The most common any-grade treatment-related AEs were hand-foot syndrome (34.25%), diarrhea (23.29%), and hypertension (21.92%). Grade ≥3 treatment-related AEs occurred in 12.3% of the patients. The most common grade 3 treatment-related AE was hypertension (5.48%).

Conclusions: TACE combined with ablation and regorafenib is an effective, safe, and promising second-line treatment option for patients with unresectable HCC after progression from first-line therapy.