Regorafenib combined with a PD-1 inhibitor in the second-line setting for unresectable hepatocellular carcinoma in real-world practice

Most advanced hepatocellular carcinoma (HCC) cases administered molecular targeted agents and/or anti-programmed cell death-1 (PD-1) inhibitors have no response or develop resistance. Moreover, second-line therapies still cannot provide beneficial clinical outcomes. A pilot study assessing combined regorafenib and PD-1 inhibitor as second-line treatment of advanced HCC reported promising effectiveness. The current single-center, retrospective, real-world study was carried out between January 2019 and July 2021. Advanced HCC cases were administered second-line regorafenib combined with a PD-1 inhibitor or regorafenib alone were assessed. Progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were determined. Totally 46 HCC cases were analyzed, most of whom underwent previous systemic treatment comprising targeted therapy and immunotherapy. Tumor response was evaluated in 25 and 21 individuals in the regorafenib + PD-1 inhibitor and regorafenib monotherapy groups, respectively: ORRs were 21.7% and 8.7%, and DCRs were 47.8% and 32.6%, respectively. Median PFS was markedly longer in the regorafenib plus PD-1 inhibitor group (11.5 months) compared with the regorafenib monotherapy group (5.1 months, P=0.049). This study suggested regorafenib and a PD-1 inhibitor in combination may provide significant clinical benefits in HCC cases showing progression following first-line treatment. Further analysis in real-world studies with large cohorts is warranted to confirm these findings.