Abstract
BACKGROUND: In patients with advanced hepatocellular carcinoma (HCC) following sorafenib failure, regorafenib has been used as an initial second-line drug. It is unclear the real efficacy and safety of sorafenib-regorafenib sequential therapy compared to placebo or other treatment (cabozantinib or nivolumab or placebo) in advanced HCC. METHODS: Four electronic databases (PubMed, Embase, Web of Science, and Ovid) were systematically searched for eligible articles from their inception to July, 2024. Included articles were selected based on strict eligibility criteria. Review Manager 5.4 software were performed for statistical analysis. RESULTS: Ten studies with 2349 HCC patients of whom 1370 received regorafenib treatment, and 979 underwent cabozantinb, nivolumab or placebo were selected for meta-analysis. The results of our systematic review and meta-analysis found regorafenib could significantly prolong overall survival (standardized mean difference [SMD] = 0.16, 95% CI = 0.02 to 0.29, P = .02) than other treatment (cabozantinib or nivolumab or placebo) in second-line treatment of HCC following sorafenib failure. No significant difference in progression-free survival (SMD = -0.03; 95% CI = -0.13 to 0.06; P = .53), overall response rate (risk ratio [RR] = 0.59; 95% CI = 0.24 to 1.47; P = .26), disease control rate (RR = 1.23; 95% CI = 0.7 to 2.16; P = .48) between 2 groups. Subgroup analysis demonstrated that nivolumab has better overall response rate results than regorafenib (RR = 0.38; 95% CI = 0.24 to 0.61; P < .0001). CONCLUSIONS: Compared with other treatment (cabozantinib or nivolumab or placebo), regorafenib seemed to be more effective for patients with HCC who have not responded to initial sorafenib treatment.