Regorafenib with immunotherapy versus regorafenib alone as second-line treatment for hepatocellular carcinoma: A multicenter real-world study

Cancer Med. 2024 May;13(9):e7236. doi: 10.1002/cam4.7236.

Abstract

Introduction: Regorafenib remains the standard and widely used second-line strategy for advanced hepatocellular carcinoma (HCC). There is still a lack of large-scale multicenter real-world evidence concerning the concurrent use of regorafenib with immune checkpoint inhibitors (ICI). This study aims to evaluate whether combining regorafenib with ICI provides greater clinical benefit than regorafenib monotherapy as second-line therapy for advanced HCC under real-world circumstances.

Patients and methods: The study included 208 patients from five medical facilities. One hundred forty-three patients received regorafenib plus ICI combination therapy, while 65 patients received regorafenib monotherapy. Propensity score matching (PSM) analysis was employed.

Results: The regorafenib plus ICI group demonstrated significantly higher objective response rate (24.3% vs. 10.3%, after PSM, p = 0.030) and disease control rate (79.4% vs. 50.0%, after PSM, p < 0.001) compared to the regorafenib monotherapy group based on mRECIST criteria. Median progression-free survival (7.9 vs. 3.2 months, after PSM, p < 0.001) and overall survival (25.6 vs. 16.4 months, p = 0.010, after PSM) were also considerably longer in the regorafenib plus ICI group. The incidence of Grades 3-4 treatment-related adverse events (TRAEs) was marginally greater in the regorafenib plus ICI group than in the regorafenib group (23.8% vs. 20.0%, p = 0.546). Notably, there were no instances of treatment-related mortality or emergence of new TRAEs in any treatment group.

Conclusion: The combination of regorafenib and ICI shows potential as a viable second-line treatment for advanced HCC, exhibiting favorable efficacy while maintaining a tolerable safety profile in contrast to regorafenib monotherapy.

Keywords: hepatocellular carcinoma; immune checkpoint inhibitor; multicenter; regorafenib; second‐line therapy.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • Carcinoma, Hepatocellular* / therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / methods
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / therapy
  • Male
  • Middle Aged
  • Phenylurea Compounds* / administration & dosage
  • Phenylurea Compounds* / adverse effects
  • Phenylurea Compounds* / therapeutic use
  • Pyridines* / therapeutic use
  • Retrospective Studies

Substances

  • regorafenib
  • Pyridines
  • Phenylurea Compounds
  • Immune Checkpoint Inhibitors