Lenvatinib plus drug-eluting bead transarterial chemoembolization with/without hepatic arterial infusion chemotherapy for hepatocellular carcinoma larger than 7 cm with major portal vein tumor thrombosis: a multicenter retrospective cohort study.

Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 101228232 Publication Model: Electronic Cited Medium: Internet ISSN: 1743-9159 (Electronic) Linking ISSN: 17439159 NLM ISO Abbreviation: Int J Surg Subsets: MEDLINE

Publication: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc.
Original Publication: London : Surgical Associates Ltd., c2004-

Carcinoma, Hepatocellular*/therapy ; Carcinoma, Hepatocellular*/drug therapy ; Carcinoma, Hepatocellular*/pathology ; Liver Neoplasms*/therapy ; Liver Neoplasms*/drug therapy ; Liver Neoplasms*/pathology ; Liver Neoplasms*/mortality ; Portal Vein* ; Chemoembolization, Therapeutic*/methods ; Quinolines*/administration & dosage ; Infusions, Intra-Arterial* ; Phenylurea Compounds*/administration & dosage ; Phenylurea Compounds*/adverse effects; Humans ; Male ; Retrospective Studies ; Female ; Middle Aged ; Aged ; Venous Thrombosis/drug therapy ; Venous Thrombosis/therapy ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Fluorouracil/administration & dosage ; China ; Adult ; Oxaliplatin/administration & dosage ; Treatment Outcome ; Antineoplastic Agents/administration & dosage

Background: The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. The authors aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC greater than 7.0 cm accompanied with major PVTT.
Materials and Methods: This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0 cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score matching (PSM).
Results: A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524).
Conclusion: The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.
(Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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;71:209–249.
Lu J, Zhang XP, Zhong BY, et al. Management of patients with hepatocellular carcinoma and portal vein tumour thrombosis: comparing east and west. Lancet Gastroenterol Hepatol 2019;4:721–730.
Sun J, Guo R, Bi X, et al. Guidelines for diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus in china (2021 Edition). Liver Cancer 2022;11:315–328.
Deng ZJ, Li L, Teng YX, et al. Treatments of hepatocellular carcinoma with portal vein tumor thrombus: current status and controversy. J Clin Transl Hepatol 2022;10:147–158.
Kudo M, Kawamura Y, Hasegawa K, et al. Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver Cancer 2021;10:181–223.
He MK, Zou RH, Li QJ, et al. Phase II study of sorafenib combined with concurrent hepatic arterial infusion of oxaliplatin, 5-fluorouracil and leucovorin for unresectable hepatocellular carcinoma with major portal vein thrombosis. Cardiovasc Intervent Radiol 2018;41:734–743.
Zheng K, Zhu X, Fu S, et al. Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib for hepatocellular carcinoma with major portal vein tumor thrombosis: a randomized trial. Radiology 2022;303:455–464.
Shui Y, Yu W, Ren X, et al. Stereotactic body radiotherapy based treatment for hepatocellular carcinoma with extensive portal vein tumor thrombosis. Radiat Oncol 2018;13:188.
Huang J, Huang W, Zhan M, et al. Drug-eluting bead transarterial chemoembolization combined with FOLFOX-based hepatic arterial infusion chemotherapy for large or huge hepatocellular carcinoma. J Hepatocell Carcinoma 2021;8:1445–1458.
Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology 2023;78:1922–1965.
Zhou J, Sun H, Wang Z, et al. Guidelines for the diagnosis and treatment of hepatocellular carcinoma (2019 Edition). Liver Cancer 2020;9:682–720.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182–236.
Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022;76:681–693.
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;391:1163–1173.
Cai M, Huang W, Huang J, et al. Transarterial chemoembolization combined with lenvatinib plus PD-1 inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study. Front Immunol 2022;13:848387.
Peng Z, Fan W, Zhu B, et al. Lenvatinib combined with transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma: a phase III, randomized clinical trial (LAUNCH). J Clin Oncol 2023;41:117–127.
Li QJ, He MK, Chen HW, et al. Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for large hepatocellular carcinoma: a randomized phase III trial. J Clin Oncol 2022;40:150–160.
Xue T, Le F, Chen R, et al. Transarterial chemoembolization for huge hepatocellular carcinoma with diameter over ten centimeters: a large cohort study. Med Oncol 2015;32:64.
Han K, Kim JH, Yoon HM, et al. Transcatheter arterial chemoembolization for infiltrative hepatocellular carcinoma: clinical safety and efficacy and factors influencing patient survival. Korean J Radiol 2014;15:464–471.
He MK, Le Y, Li QJ, et al. Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma: a prospective non-randomized study. Chin J Cancer 2017;36:83.
Lyu N, Kong Y, Mu L, et al. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol 2018;69:60–69.
Lyu N, Wang X, Li JB, et al. Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: a biomolecular exploratory, randomized, phase III trial (FOHAIC-1). J Clin Oncol 2022;40:468–480.
Mathew G, Agha R, Albrecht J, et al. STROCSS 2021: Strengthening the reporting of cohort, cross-sectional and case-control studies in surgery. Int J Surg 2021;96:106165.
Zhou J, Sun HC, Wang Z, et al. Guidelines for diagnosis and treatment of primary liver cancer in china (2017 Edition). Liver Cancer 2018;7:235–260.
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;68:723–750.
Chinese College of Interventionalists, Chinese Medical Doctor Association. Chinese Clinical Practice Guidelines for transarterial chemoembolization of hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi 2019;27:172–181.
Lencioni R, de Baere T, Burrel M, et al. Transcatheter treatment of hepatocellular carcinoma with Doxorubicin-loaded DC Bead (DEBDOX): technical recommendations. Cardiovasc Intervent Radiol 2012;35:980–985.
He M, Li Q, Zou R, et al. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: a randomized clinical trial. Jama Oncol 2019;5:953–960.
Liu BJ, Gao S, Zhu X, et al. Sorafenib combined with embolization plus hepatic arterial infusion chemotherapy for inoperable hepatocellular carcinoma. World J Gastrointest Oncol 2020;12:663–676.
Guo Y, Wu J, Liang L, et al. Tyrosine-kinase inhibitor combined with iodine-125 seed brachytherapy for hepatocellular carcinoma refractory to transarterial chemoembolization: a propensity-matched study. Cancer Imaging 2023;23:91.
Austin PC. Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations. Biom J 2009;51:171–184.
Xia D, Bai W, Wang E, et al. Lenvatinib with or without concurrent drug-eluting beads transarterial chemoembolization in patients with unresectable, advanced hepatocellular carcinoma: a real-world, multicenter, retrospective study. Liver Cancer 2022;11:368–382.
Fan W, Zhu B, Yue S, et al. Idarubicin-loaded DEB-TACE plus Lenvatinib versus Lenvatinib for patients with advanced hepatocellular carcinoma: a propensity score-matching analysis. Cancer Med 2023;12:61–72.
Li B, Qiu J, Zheng Y, et al. Conversion to resectability using transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for initially unresectable hepatocellular carcinoma. Ann Surg Open 2021;2:e57.
Chang Y, Jeong SW, Young JJ, et al. Recent updates of transarterial chemoembolilzation in hepatocellular carcinoma. Int J Mol Sci 2020;21:8165.
Lammer J, Malagari K, Vogl T, et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 2010;33:41–52.
Liu Y, Huang W, He M, et al. Efficacy and safety of callispheres drug-eluting beads transarterial chemoembolization in barcelona clinic liver cancer stage C patients. Oncol Res 2019;27:565–573.
Yuan Y, He W, Yang Z, et al. TACE-HAIC combined with targeted therapy and immunotherapy versus TACE alone for hepatocellular carcinoma with portal vein tumour thrombus: a propensity score matching study. Int J Surg 2023;109:1222–1230.
Ding X, Sun W, Li W, et al. Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: a prospective randomized study. Cancer-Am Cancer Soc 2021;127:3782–3793.

ClinicalTrials.gov NCT06265883

EE083865G2 (lenvatinib)
0 (Quinolines)
0 (Phenylurea Compounds)
U3P01618RT (Fluorouracil)
04ZR38536J (Oxaliplatin)
0 (Antineoplastic Agents)

Date Created: 20240613 Date Completed: 20250114 Latest Revision: 20250114

20250114

PMC11634077

10.1097/JS9.0000000000001819

38869974