Efficacy and Safety of Regorafenib Plus Immune Checkpoint Inhibitors with or Without TACE as a Second-Line Treatment for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis

References

• Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660
   PubMed Web of Science ®Google Scholar
• Fitzmaurice C, Allen C, Barber RM, et al.; Global Burden of Disease Cancer C. Global, Regional, and National cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3(4):524–548. doi:10.1001/jamaoncol.2016.5688
   PubMed Web of Science ®Google Scholar
• Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–390. doi:10.1056/NEJMoa0708857
   PubMed Web of Science ®Google Scholar
• Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a Phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34. doi:10.1016/S1470-2045(08)70285-7
   PubMed Web of Science ®Google Scholar
• Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised Phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–1173. doi:10.1016/S0140-6736(18)30207-1
   PubMed Web of Science ®Google Scholar
• Bruix J, Qin S, Merle P, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66. doi:10.1016/S0140-6736(16)32453-9
   PubMed Web of Science ®Google Scholar
• Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63. doi:10.1056/NEJMoa1717002
   PubMed Web of Science ®Google Scholar
• Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282–296. doi:10.1016/S1470-2045(18)30937-9
   PubMed Web of Science ®Google Scholar
• Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation Barcelona Clinic Liver Cancer (BCLC) staging system. The 2022 update. J Hepatol. 2021. doi:10.1016/j.jhep.2021.11.018
   Web of Science ®Google Scholar
• Wang D, Yang X, Lin J, et al. Comparing the efficacy and safety of second-line therapies for advanced hepatocellular carcinoma: a network meta-analysis of phase III trials. Therap Adv Gastroenterol. 2020;13:1756284820932483. doi:10.1177/1756284820932483
   Web of Science ®Google Scholar
• Zhu AX, Finn RS, Edeline J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Clinical Trial, Phase II Multicenter Study Research Support, Non-U.S. Gov’t. Lancet Oncol. 2018;19(7):940–952. doi:10.1016/S1470-2045(18)30351-6
   PubMed Web of Science ®Google Scholar
• El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Clinical Trial, Phase I Clinical Trial, Phase II Multicenter Study. Lancet. 2017;389(10088):2492–2502. doi:10.1016/S0140-6736(17)31046-2
   PubMed Web of Science ®Google Scholar
• Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol. 2020;21(4):571–580. doi:10.1016/S1470-2045(20)30011-5
   PubMed Web of Science ®Google Scholar
• European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236. doi:10.1016/j.jhep.2018.03.019
   PubMed Web of Science ®Google Scholar
• Zhou J, Sun H, Wang Z, et al. Guidelines for the diagnosis and treatment of hepatocellular carcinoma (2019 edition). Liver Cancer. 2020;9(6):682–720. doi:10.1159/000509424
   PubMed Web of Science ®Google Scholar
• Cheu JW, Wong CC. Mechanistic rationales guiding combination hepatocellular carcinoma therapies involving immune checkpoint inhibitors. Hepatology. 2021;74(4):2264–2276. doi:10.1002/hep.31840
   PubMed Web of Science ®Google Scholar
• Wang B, Xu H, Gao ZQ, Ning HF, Sun YQ, Cao GW. Increased expression of vascular endothelial growth factor in hepatocellular carcinoma after transcatheter arterial chemoembolization. Acta Radiol. 2008;49(5):523–529. doi:10.1080/02841850801958890
   PubMed Web of Science ®Google Scholar
• Personeni N, Pressiani T, Santoro A, Rimassa L. Regorafenib in hepatocellular carcinoma: latest evidence and clinical implications. Drugs Context. 2018;7:212533. doi:10.7573/dic.212533
   PubMedGoogle Scholar
• Zhou G, Sprengers D, Boor PPC, et al. Antibodies against immune checkpoint molecules restore functions of tumor-infiltrating T cells in hepatocellular carcinomas. Gastroenterology. 2017;153(4):1107–1119 e10. doi:10.1053/j.gastro.2017.06.017
   PubMed Web of Science ®Google Scholar
• Shigeta K, Matsui A, Kikuchi H, et al. Regorafenib combined with PD1 blockade increases CD8 T-cell infiltration by inducing CXCL10 expression in hepatocellular carcinoma. J Immunother Cancer. 2020;8(2):e001435. doi:10.1136/jitc-2020-001435
   PubMed Web of Science ®Google Scholar
• Suner A, Carr BI. Platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios predict tumor size and survival in HCC patients: retrospective study. Ann Med Surg. 2020;58:167–171. doi:10.1016/j.amsu.2020.08.042
   PubMed Web of Science ®Google Scholar
• Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(1):52–60. doi:10.1055/s-0030-1247132
   PubMed Web of Science ®Google Scholar
• Li S, Lyu N, Han X, et al. Hepatic artery infusion chemotherapy using fluorouracil, leucovorin, and oxaliplatin versus transarterial chemoembolization as initial treatment for locally advanced hepatocellular carcinoma: a propensity score-matching analysis. J Vasc Interv Radiol. 2021;32(9):1267–1276 e1. doi:10.1016/j.jvir.2021.06.008
   PubMed Web of Science ®Google Scholar
• El-Khoueiry AB, Kim RD, Harris WP, et al. Updated results of a phase 1b study of regorafenib (REG) 80 mg/day or 120 mg/day plus pembrolizumab (PEMBRO) for first-line treatment of advanced hepatocellular carcinoma (HCC). J Clin Oncol. 2021;39(15_suppl):4078. doi:10.1200/JCO.2021.39.15_suppl.4078
   Web of Science ®Google Scholar
• Huang J, Guo Y, Huang W, et al. Regorafenib combined with PD-1 blockade immunotherapy versus regorafenib as second-line treatment for advanced hepatocellular carcinoma: a multicenter retrospective study. J Hepatocell Carcinoma. 2022;9:157–170. doi:10.2147/JHC.S353956
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Buque A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17(2):97–111. doi:10.1038/nri.2016.107
   PubMed Web of Science ®Google Scholar
• Zhou J, Sun HC, Wang Z, et al. Guidelines for diagnosis and treatment of primary liver cancer in China (2017 edition). Liver Cancer. 2018;7(3):235–260. doi:10.1159/000488035
   PubMed Web of Science ®Google Scholar
• Kim HD, Bang Y, Lee MA, et al. Regorafenib in patients with advanced Child-Pugh B hepatocellular carcinoma: a multicentre retrospective study. Liver Int. 2020;40(10):2544–2552. doi:10.1111/liv.14573
   PubMed Web of Science ®Google Scholar
• Schobert IT, Savic LJ, Chapiro J, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE. Eur Radiol. 2020;30(10):5663–5673. doi:10.1007/s00330-020-06931-5
   PubMed Web of Science ®Google Scholar
• Zhang L, Yan ZP, Hou ZH, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of outcomes in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization plus sorafenib. Front Mol Biosci. 2021;8:624366. doi:10.3389/fmolb.2021.624366
   PubMedGoogle Scholar
• Bambace NM, Holmes CE. The platelet contribution to cancer progression. J Thromb Haemost. 2011;9(2):237–249. doi:10.1111/j.1538-7836.2010.04131.x
   PubMed Web of Science ®Google Scholar
• van der Woude LL, Gorris MAJ, Halilovic A, Figdor CG, de Vries IJM. Migrating into the Tumor: a Roadmap for T Cells. Trends Cancer. 2017;3(11):797–808. doi:10.1016/j.trecan.2017.09.006
   PubMed Web of Science ®Google Scholar
• Han Y, Cao G, Sun B, et al. Regorafenib combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: a real-world study. BMC Gastroenterol. 2021;21(1):393. doi:10.1186/s12876-021-01967-3
   PubMed Web of Science ®Google Scholar