269
Views
0
CrossRef citations to date
0
Altmetric
ORIGINAL RESEARCH

Efficacy and Safety of TACE Combined with Regorafenib Plus PD-1 Inhibitor in the Treatment of Hepatocellular Carcinoma After Sorafenib Resistance

, , &
Pages 267-279 | Received 01 Dec 2022, Accepted 07 Feb 2023, Published online: 16 Feb 2023

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
  • Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723–750. doi:10.1002/hep.29913
  • European Association for the Study of the Liver. Electronic address: [email protected]; European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236. doi:10.1016/j.jhep.2018.03.019
  • Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM, Lynch M. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther. 2008;7(10):3129–3140. doi:10.1158/1535-7163
  • Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004;64(19):7099–7109. doi:10.1158/0008-5472
  • 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
  • Kudo M, Ueshima K, Ikeda M, et al. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut. 2020;69(8):1492–1501. doi:10.1136/gutjnl-2019-318934
  • Finn RS, Zhu AX, Farah W, et al. Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: a systematic review and meta-analysis. Hepatology. 2018;67(1):422–435. doi:10.1002/hep.29486
  • Bruix J, Raoul JL, Sherman M, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a Phase III trial. J Hepatol. 2012;57(4):821–829. doi:10.1016/j.jhep.2012.06.014
  • Park JW, Koh YH, Kim HB, et al. Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma. J Hepatol. 2012;56(6):1336–1342. doi:10.1016/j.jhep.2012.01.006
  • 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
  • Fung AS, Tam VC, Meyers DE, et al. Second-line treatment of hepatocellular carcinoma after sorafenib: characterizing treatments used over the past 10 years and real-world eligibility for cabozantinib, regorafenib, and ramucirumab. Cancer Med. 2020;9(13):4640–4647. doi:10.1002/cam4.3116
  • Teufel M, Seidel H, Köchert K, et al. Biomarkers associated with response to regorafenib in patients with hepatocellular carcinoma. Gastroenterology. 2019;156(6):1731–1741. doi:10.1053/j.gastro.2019.01.261
  • Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 2011;129(1):245–255. doi:10.1002/ijc.25864
  • 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
  • Elseud YA, Shaaban A, Mohanty A, Albarrak J. Safety and tolerability of regorafenib: a real-life experience. J Gastrointest Cancer. 2022;53(1):187–191. doi:10.1007/s12029-020-00570-1
  • Lee MJ, Chang SW, Kim JH, et al. Real-world systemic sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Korea. Invest New Drugs. 2021;39(1):260–268. doi:10.1007/s10637-020-00977-4
  • Kim K, Jha R, Prins PA, et al. Regorafenib in advanced hepatocellular carcinoma (HCC): considerations for treatment. Cancer Chemother Pharmacol. 2017;80(5):945–954. doi:10.1007/s00280-017-3431-5
  • Ogasawara S, Ooka Y, Itokawa N, et al. Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan. Invest New Drugs. 2020;38(1):172–180. doi:10.1007/s10637-019-00801-8
  • Abou-Elkacem L, Arns S, Brix G, et al. Regorafenib inhibits growth, angiogenesis, and metastasis in a highly aggressive, orthotopic colon cancer model. Mol Cancer Ther. 2013;12(7):1322–1331. doi:10.1158/1535-7163
  • 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
  • Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-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
  • Hiraoka A, Kumada T, Tada T, et al. Therapeutic efficacy of ramucirumab after lenvatinib for post-progression treatment of unresectable hepatocellular carcinoma. Gastroenterol Rep. 2020;9(2):133–138. doi:10.1093/gastro/goaa042
  • Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, Chumsri S, Lou Y. Next generation of immune checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol. 2018;11(1):39. doi:10.1186/s13045-018-0582-8
  • He X, Xu C. Immune checkpoint signaling and cancer immunotherapy. Cell Res. 2020;30(8):660–669. doi:10.1038/s41422-020-0343-4
  • 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. Lancet. 2017;389(10088):2492–2502. doi:10.1016/S0140-6736(17)31046-2
  • 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. Lancet Oncol. 2018;19(7):940–952. doi:10.1016/S1470-2045(18)30351-6
  • 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
  • Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–1905. doi:10.1056/NEJMoa1915745
  • Kudo M. Scientific rationale for combined immunotherapy with PD-1/PD-L1 antibodies and VEGF inhibitors in advanced hepatocellular carcinoma. Cancers. 2020;12(5):1089. doi:10.3390/cancers12051089
  • Ren Z, Xu J, Bai Y, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2–3 study. Lancet Oncol. 2021;22(7):977–990. doi:10.1016/S1470-2045(21)00252-7
  • Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–1314. doi:10.1016/S0140-6736(18)30010-2
  • Li X, Feng GS, Zheng CS, Zhuo CK, Liu X. Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol. 2004;10(19):2878–2882. doi:10.3748/wjg.v10.i19.2878
  • Sergio A, Cristofori C, Cardin R, et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol. 2008;103(4):914–921. doi:10.1111/j.1572-0241.2007.01712.x
  • Wang H, Xiao W, Han Y, et al. Study on safety and efficacy of regorafenib combined with transcatheter arterial chemoembolization in the treatment of advanced hepatocellular carcinoma after first-line targeted therapy. J Gastrointest Oncol. 2022;13(3):1248–1254. doi:10.21037/jgo-22-395
  • 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
  • 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
  • Renzulli M, Peta G, Vasuri F, et al. Standardization of conventional chemoembolization for hepatocellular carcinoma. Ann Hepatol. 2021;22:100278. doi:10.1016/j.aohep.2020.10.006
  • Prajapati HJ, Xing M, Spivey JR, et al. Survival, efficacy, and safety of small versus large doxorubicin drug-eluting beads TACE chemoembolization in patients with unresectable HCC. AJR Am J Roentgenol. 2014;203(6):W706–W714. doi:10.2214/AJR.13.12308
  • 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
  • Basch E, Reeve BB, Mitchell SA, et al. Development of the National Cancer Institute’s patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst. 2014;106(9):dju244. doi:10.1093/jnci/dju244
  • Liu K, Wu J, Xu Y, Li D, Huang S, Mao Y. Efficacy and safety of regorafenib with or without PD-1 inhibitors as second-line therapy for advanced hepatocellular carcinoma in real-world clinical practice. Onco Targets Ther. 2022;15:1079–1094. doi:10.2147/OTT.S383685
  • Hiraoka A, Kumada T, Kudo M, et al. Hepatic function during repeated TACE procedures and prognosis after introducing sorafenib in patients with unresectable hepatocellular carcinoma: multicenter analysis. Dig Dis. 2017;35(6):602–610. doi:10.1159/000480256
  • Liu K, Min XL, Peng J, Yang K, Yang L, Zhang XM. The changes of HIF-1α and VEGF expression after TACE in patients with hepatocellular carcinoma. J Clin Med Res. 2016;8(4):297–302. doi:10.14740/jocmr2496w
  • Liu P, Atkinson SJ, Akbareian SE, et al. Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling. Sci Rep. 2017;7(1):12651. doi:10.1038/s41598-017-12855-w
  • Freedman SJ, Sun ZY, Poy F, et al. Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha. Proc Natl Acad Sci USA. 2002;99(8):5367–5372. doi:10.1073/pnas.082117899
  • Zopf D, Fichtner I, Bhargava A, et al. Pharmacologic activity and pharmacokinetics of metabolites of regorafenib in preclinical models. Cancer Med. 2016;5(11):3176–3185. doi:10.1002/cam4.883
  • Rimassa L, Pressiani T, Personeni N, Santoro A. Regorafenib for the treatment of unresectable hepatocellular carcinoma. Expert Rev Anticancer Ther. 2017;17(7):567–576. doi:10.1080/14737140.2017.1338955
  • Wu RY, Kong PF, Xia LP, et al. Regorafenib promotes antitumor immunity via inhibiting PD-L1 and IDO1 expression in melanoma. Clin Cancer Res. 2019;25(14):4530–4541. doi:10.1158/1078-0432.CCR-18-2840
  • Hato T, Zhu AX, Duda DG. Rationally combining anti-VEGF therapy with checkpoint inhibitors in hepatocellular carcinoma. Immunotherapy. 2016;8(3):299–313. doi:10.2217/imt.15.126
  • Elovic AE, Ohyama H, Sauty A, et al. IL-4-dependent regulation of TGF-alpha and TGF-beta1 expression in human eosinophils. J Immunol. 1998;160(12):6121–6127.
  • Myojin Y, Kodama T, Sakamori R, et al. Interleukin-6 is a circulating prognostic biomarker for hepatocellular carcinoma patients treated with combined immunotherapy. Cancers. 2022;14(4):883. doi:10.3390/cancers14040883
  • Cannarile MA, Weisser M, Jacob W, Jegg AM, Ries CH, Rüttinger D. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017;5(1):53. doi:10.1186/s40425-017-0257-y
  • Pinato DJ, Murray SM, Forner A, et al. Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy. J Immunother Cancer. 2021;9(9):e003311. doi:10.1136/jitc-2021-003311
  • Kudo M. Combination cancer immunotherapy with molecular targeted agents/anti-CTLA-4 antibody for hepatocellular carcinoma. Liver Cancer. 2019;8(1):1–11. doi:10.1159/000496277
  • Teng MW, Ngiow SF, Ribas A, Smyth MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res. 2015;75(11):2139–2145. doi:10.1158/0008-5472
  • Shi F, Shi M, Zeng Z, et al. PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer. 2011;128(4):887–896. doi:10.1002/ijc.25397
  • Gao Q, Wang XY, Qiu SJ, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009;15(3):971–979. doi:10.1158/1078-0432
  • Kabashima A, Shimada S, Shimokawa M, Akiyama Y, Tanabe M, Tanaka S. Molecular and immunological paradigms of hepatocellular carcinoma: special reference to therapeutic approaches. J Hepatobiliary Pancreat Sci. 2021;28(1):62–75. doi:10.1002/jhbp.874
  • Shembrey C, Huntington ND, Hollande F. Impact of tumor and immunological heterogeneity on the anti-cancer immune response. Cancers. 2019;11(9):1217. doi:10.3390/cancers11091217
  • Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197–218. doi:10.1038/s41573-018-0007-y
  • Sia D, Jiao Y, Martinez-Quetglas I, et al. Identification of an immune-specific class of hepatocellular carcinoma, based on molecular features. Gastroenterology. 2017;153(3):812–826. doi:10.1053/j.gastro.2017.06.007
  • Shimada S, Mogushi K, Akiyama Y, et al. Comprehensive molecular and immunological characterization of hepatocellular carcinoma. EBioMedicine. 2019;40:457–470. doi:10.1016/j.ebiom.2018.12.058
  • Haanen JBAG. Converting cold into hot tumors by combining immunotherapies. Cell. 2017;170(6):1055–1056. doi:10.1016/j.cell.2017.08.031
  • Sagnelli E, Sagnelli C, Macera M, Pisaturo M, Coppola N. An update on the treatment options for HBV/HCV coinfection. Expert Opin Pharmacother. 2017;18(16):1691–1702. doi:10.1080/14656566.2017.1398233
  • World Health Organization. Guidelines for the Screening Care and Treatment of Persons with Chronic Hepatitis C Infection: Updated Version. Geneva: World Health Organization; 2016.
  • Jiang XW, Ye JZ, Li YT, Li LJ. Hepatitis B reactivation in patients receiving direct-acting antiviral therapy or interferon-based therapy for hepatitis C: a systematic review and meta-analysis. World J Gastroenterol. 2018;24(28):3181–3191. doi:10.3748/wjg.v24.i28.3181
  • Chen G, Wang C, Chen J, et al. Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: a systematic review and meta-analysis. Hepatology. 2017;66(1):13–26. doi:10.1002/hep.29109
  • Mavilia MG, Wu GY. HBV-HCV coinfection: viral interactions, management, and viral reactivation. J Clin Transl Hepatol. 2018;6(3):296–305. doi:10.14218/JCTH.2018.00016
  • Liu CJ. Treatment of patients with dual hepatitis C virus and hepatitis B virus infection: resolved and unresolved issues. J Gastroenterol Hepatol. 2014;29(1):26–30. doi:10.1111/jgh.12421
  • Gish RG. HBV/HCV coinfection and possible reactivation of HBV following DAA use. Gastroenterol Hepatol. 2017;13(5):292–295.
  • Granito A, Marinelli S, Forgione A, et al. Regorafenib combined with other systemic therapies: exploring promising therapeutic combinations in HCC. J Hepatocell Carcinoma. 2021;8:477–492. doi:10.2147/JHC.S251729