Background: The treatment of advanced hepatocellular carcinoma (HCC) is challenging. The positive effect of gelatin sponge microparticles for transarterial chemoembolization (GSMs-TACE) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C and large HCC has been confirmed by previous studies. This study initially explored the efficacy and safety of GSMs-TACE combined with regorafenib in patients with unresectable HCC who failed first-line sorafenib and/or lenvatinib therapy.

Methods: This retrospective study collated the data of patients who presented at the Affiliated Zhongshan Hospital of Dalian University between December 2018 and June 2021. Patients were treated with GSMs-TACE, followed by regorafenib 1 week later. Follow-up was conducted every 3 to 5 weeks after combination therapy. If the treatment was changed due to disease progression, the patients were followed up every 3 months to obtain overall survival (OS) time. The OS, progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) was used to evaluate the efficacy of the treatment, while adverse events (AEs) was used to assess its safety.

Results: A total of 47 patients were included in the study. The age of patients was 64.4±6.8 years; There were 43 (91.5%) males and 4 (8.5%) females; the number of Child-Pugh grade A was 22 (46.8%) and B was 25 (53.2%); the longest tumor diameter was 5.1 cm [interquartile range (IQR), 3.8, 8.9 cm]; the number of BCLC grade B was 14 (29.8%) and grade C was 33 (70.2%). The median follow-up time was 11.6 months [95% confidence interval (CI): 10.8 to 14.0 months]. The median number of GSMS-TACE sessions was 3. The initial doses of regorafenib were 80 mg/d (n=17, 36.2%), 120 mg/d (n=23, 48.9%), and 160 mg/d (n=7, 14.9%). The median PFS was 6.0 months (95% CI: 4.5 to 7.5 months), and the median OS was 14.3 months (95% CI: 11.8 to 16.8 months). The ORR and DCR were 21.3% and 85.1%, respectively. The incidence of grade 3/4 AEs was 8 out of 47 patients (17.0%).

Conclusions: The study indicated that GSMs-TACE combined with regorafenib may be efficient and safe in patients with unresectable HCC. Future prospective large-scale studies should be conducted to verify these results.