Regorafenib Combined with PD-1 Blockade Immunotherapy versus Regorafenib as Second-Line Treatment for Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Study

PURPOSE: To evaluate the safety and efficacy of regorafenib combined with anti-PD-1 antibody sintilimab (rego-sintilimab) as a second-line treatment for advanced hepatocellular carcinoma (HCC). METHODS: This multicenter retrospective study evaluated consecutive patients with advanced HCC who received rego-sintilimab (rego-sintilimab group) or regorafenib alone (regorafenib group) as a second-line treatment from January 2019 to December 2020. Adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Uni- and multi-variable analyses of prognostic factors for OS and PFS were performed using Cox proportional hazard regression models. RESULTS: In total, 113 patients were included in the study: 58 received rego-sintilimab and 55 received regorafenib. The rego-sintilimab group had higher ORR (36.2% vs 16.4%, P = 0.017), longer PFS (median 5.6 vs 4.0 months; P = 0.045), and better OS (median 13.4 vs 9.9 months; P = 0.023) than the regorafenib group. Regorafenib alone, Child-Pugh B, and neutrophil-to-lymphocyte ratio (NLR) > 3.6 were independent prognostic factors for poor OS. Regorafenib alone, α-fetoprotein level, and NLR > 3.6 were independent prognostic factors for poor PFS. Subgroup analyses showed a survival benefit of rego-sintilimab in patients with NLR ≤ 3.6 (hazard ratio 0.518 [95% CI, 0.257–0.955]) but not in those with NLR > 3.6 (0.852 [0.461–1.572]); P = 0.002 for interaction. The difference in incidence of grade 3/4 adverse events between the two groups was not statistically significant (39.7% vs 30.9%; P = 0.331). CONCLUSION: Rego-sintilimab was tolerated and led to better OS than regorafenib as a second-line treatment for advanced HCC patients, especially in those with NLR ≤ 3.6.