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

Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE

Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012-

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

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.
(© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

N Engl J Med. 2008 Jul 24;359(4):378-90. (PMID: 18650514)
J Gastrointest Oncol. 2022 Jun;13(3):1278-1288. (PMID: 35837155)
Clin Cancer Res. 2019 Jul 15;25(14):4530-4541. (PMID: 30940655)
Lancet Oncol. 2015 Jul;16(7):859-70. (PMID: 26095784)
Ther Clin Risk Manag. 2023 Apr 05;19:329-339. (PMID: 37041973)
Nat Rev Dis Primers. 2020 May 7;6(1):38. (PMID: 32382051)
J Hepatocell Carcinoma. 2022 Mar 10;9:157-170. (PMID: 35300208)
CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338)
J Hepatocell Carcinoma. 2021 May 26;8:477-492. (PMID: 34079777)
N Engl J Med. 2018 Jul 05;379(1):54-63. (PMID: 29972759)
Onco Targets Ther. 2022 Oct 01;15:1079-1094. (PMID: 36212725)
J Hepatol. 2012 Apr;56(4):908-43. (PMID: 22424438)
Int Immunopharmacol. 2022 Dec;113(Pt B):109401. (PMID: 36395672)
Clin Cancer Res. 2014 Nov 15;20(22):5768-76. (PMID: 25248379)
J Clin Oncol. 2015 Feb 20;33(6):550-8. (PMID: 25512453)
Lancet. 2018 Mar 24;391(10126):1163-1173. (PMID: 29433850)
Hepatology. 2020 Apr;71(4):1247-1261. (PMID: 31378984)
Cancer Med. 2024 May;13(9):e7236. (PMID: 38716585)
J Immunother Cancer. 2020 Nov;8(2):. (PMID: 33234602)
J Hepatol. 2016 Mar;64(3):601-8. (PMID: 26551516)
J Hepatol. 2020 Feb;72(2):288-306. (PMID: 31954493)
N Engl J Med. 2020 May 14;382(20):1894-1905. (PMID: 32402160)
Lancet. 2017 Jan 7;389(10064):56-66. (PMID: 27932229)
J Clin Oncol. 2020 Sep 10;38(26):2960-2970. (PMID: 32716739)
Hepatology. 2011 Mar;53(3):1020-2. (PMID: 21374666)
Lancet. 2022 Oct 15;400(10360):1345-1362. (PMID: 36084663)

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

24T2A1DOYB (regorafenib)
0 (Pyridines)
0 (Phenylurea Compounds)
0 (Immune Checkpoint Inhibitors)

Date Created: 20240508 Date Completed: 20240508 Latest Revision: 20240617

20240618

PMC11077333

10.1002/cam4.7236

38716585