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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 4
Apr.  2021
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Article Contents

Application of combined therapy with molecular-targeted drugs and immune checkpoint inhibitors and other combined therapies in hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2021.04.043
  • Received Date: 2020-09-20
  • Accepted Date: 2020-11-25
  • Published Date: 2021-04-20
  • Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and its features of insidious onset, rapid development, and high recurrence bring great challenges to the long-term survival of HCC patients. Molecular-targeted drugs and immune checkpoint inhibitors have become the research hotspots in the treatment of HCC, and a large number of clinical trials have found that combined therapy has achieved a good clinical effect. This article mainly introduces the application of combined therapy with molecular-targeted drugs and immune checkpoint inhibitors and other combined therapies in HCC and points out that combined therapy related to systemic therapy or local therapy has become the latest research hotspot in HCC treatment.

     

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  • [1]
    FENG RM, ZONG YN, CAO SM, et al. Current cancer situation in China: Good or bad news from the 2018 Global Cancer Statistics?[J]. Cancer Commun (Lond), 2019, 39(1): 22. DOI: 10.1186/s40880-019-0368-6.
    [2]
    European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma[J]. J Hepatol, 2012, 56(4): 908-943. DOI: 10.1016/j.jhep.2011.12.001.
    [3]
    HUANG A, YANG XR, CHUNG WY, et al. Targeted therapy for hepatocellular carcinoma[J]. Signal Transduct Target Ther, 2020, 5(1): 146. DOI: 10.1038/s41392-020-00264-x.
    [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[J]. Lancet, 2017, 389(10088): 2492-2502. DOI: 10.1016/S0140-6736(17)31046-2.
    [5]
    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[J]. Lancet Oncol, 2018, 19(7): 940-952. DOI: 10.1016/S1470-2045(18)30351-6.
    [6]
    FUKUMURA D, KLOEPPER J, AMOOZGAR Z, et al. Enhancing cancer immunotherapy using antiangiogenics: Opportunities and challenges[J]. Nat Rev Clin Oncol, 2018, 15(5): 325-340. DOI: 10.1038/nrclinonc.2018.29.
    [7]
    LEE MS, RYOO BY, HSU CH, et al. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): An open-label, multicentre, phase 1b study[J]. Lancet Oncol, 2020, 21(6): 808-820. DOI: 10.1016/S1470-2045(20)30156-X.
    [8]
    FINN RS, QIN S, IKEDA M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382(20): 1894-1905. DOI: 10.1056/NEJMoa1915745.
    [9]
    FINN RS, IKEDA M, ZHU AX, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma[J]. J Clin Oncol, 2020, 38(26): 2960-2970. DOI: 10.1200/JCO.20.00808.
    [10]
    XU J, ZHANG Y, JIA R, et al. Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: An open-label, dose escalation and expansion study[J]. Clin Cancer Res, 2019, 25(2): 515-523. DOI: 10.1158/1078-0432.CCR-18-2484.
    [11]
    PARDOLL DM. The blockade of immune checkpoints in cancer immunotherapy[J]. Nat Rev Cancer, 2012, 12(4): 252-264. DOI: 10.1038/nrc3239.
    [12]
    JIANG Y, LI Y, ZHU B. T-cell exhaustion in the tumor microenvironment[J]. Cell Death Dis, 2015, 6: e1792. DOI: 10.1038/cddis.2015.162.
    [13]
    CHENG H, SUN G, CHEN H, et al. Trends in the treatment of advanced hepatocellular carcinoma: Immune checkpoint blockade immunotherapy and related combination therapies[J]. Am J Cancer Res, 2019, 9(8): 1536-1545. http://www.ncbi.nlm.nih.gov/pubmed/31497341
    [14]
    POL J, VACCHELLI E, ARANDA F, et al. Trial watch: Immunogenic cell death inducers for anticancer chemotherapy[J]. Oncoimmunology, 2015, 4(4): e1008866. DOI: 10.1080/2162402X.2015.1008866.
    [15]
    McDONNELL AM, LESTERHUIS WJ, KHONG A, et al. Tumor-infiltrating dendritic cells exhibit defective cross-presentation of tumor antigens, but is reversed by chemotherapy[J]. Eur J Immunol, 2015, 45(1): 49-59. DOI: 10.1002/eji.201444722.
    [16]
    YAU T, KANG YK, KIM TY, et al. Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040[J]. J Clin Oncol, 2019, 37(Suppl): 4012.
    [17]
    KELLEY R, SANGRO B, HARRIS W, et al. Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC)[J]. J Clin Oncol, 2020, 38(Suppl): 4508. http://www.researchgate.net/publication/341629249_Efficacy_tolerability_and_biologic_activity_of_a_novel_regimen_of_tremelimumab_T_in_combination_with_durvalumab_D_for_patients_pts_with_advanced_hepatocellular_carcinoma_aHCC
    [18]
    POL J, VACCHELLI E, ARANDA F, et al. Trial watch: Immunogenic cell death inducers for anticancer chemotherapy[J]. Oncoimmunology, 2015, 4(4): e1008866. DOI: 10.1080/2162402X.2015.1008866.
    [19]
    QIN SK, CHEN ZD, LIU Y, et al. A phase Ⅱ study of anti-PD-1 antibody camrelizumab plus FOLFOX4 or GEMOX systemic chemotherapy as first-line therapy for advanced hepatocellular carcinoma or biliary tract cancer[J]. J Clin Oncol, 2019, 37(Suppl): 4074. http://www.researchgate.net/publication/333406920_A_phase_II_study_of_anti-PD-1_antibody_camrelizumab_plus_FOLFOX4_or_GEMOX_systemic_chemotherapy_as_first-line_therapy_for_advanced_hepatocellular_carcinoma_or_biliary_tract_cancer
    [20]
    MAI QC, MO ZQ, SHI F, et al. Lenvatinib plus hepatic arterial infusion of modified FOLFOX regime in patients with advanced hepatocellular carcinoma[J]. J Clin Oncol, 2020, 38(Suppl. e1): 16603. http://www.researchgate.net/publication/341628918_Lenvatinib_plus_hepatic_arterial_infusion_of_modified_FOLFOX_regime_in_patients_with_advanced_hepatocellular_carcinoma
    [21]
    GU YK, ZHANG TQ, HUANG ZL, et al. Hepatic artery infusion chemotherapy combined with apatinib and toripalimab in advanced hepatocellular carcinoma: Real-world data from a single center[J] J Clin Oncol, 2020, 38(Suppl. e1): 6602. http://www.researchgate.net/publication/341637077_Hepatic_artery_infusion_chemotherapy_combined_with_apatinib_and_toripalimab_in_advanced_hepatocellular_carcinoma_Real-world_data_from_a_single_center
    [22]
    HANAHAN D, WEINBERG RA. Hallmarks of cancer: The next generation[J]. Cell, 2011, 144(5): 646-674. DOI: 10.1016/j.cell.2011.02.013.
    [23]
    CHONG EA, MELENHORST JJ, LACEY SF, et al. PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: Refueling the CAR[J]. Blood, 2017, 129(8): 1039-1041. DOI: 10.1182/blood-2016-09-738245.
    [24]
    HECZEY A, LOUIS CU, SAVOLDO B, et al. CAR T cells administered in combination with lymphodepletion and PD-1 inhibition to patients with neuroblastoma[J]. Mol Ther, 2017, 25(9): 2214-2224. DOI: 10.1016/j.ymthe.2017.05.012.
    [25]
    WU X, LUO H, SHI B, et al. Combined antitumor effects of sorafenib and GPC3-CAR T cells in mouse models of hepatocellular carcinoma[J]. Mol Ther, 2019, 27(8): 1483-1494. DOI: 10.1016/j.ymthe.2019.04.020.
    [26]
    GUO X, JIANG H, SHI B, et al. Disruption of PD-1 enhanced the anti-tumor activity of chimeric antigen receptor T cells against hepatocellular carcinoma[J]. Front Pharmacol, 2018, 9: 1118. DOI: 10.3389/fphar.2018.01118.
    [27]
    dal BO M, de MATTIA E, BABOCI L, et al. New insights into the pharmacological, immunological, and CAR-T-cell approaches in the treatment of hepatocellular carcinoma[J]. Drug Resist Updat, 2020, 51: 100702. DOI: 10.1016/j.drup.2020.100702.
    [28]
    CHEN W, CHIANG CL, DAWSON LA. Efficacy and safety of radiotherapy for primary liver cancer[J]. Chin Clin Oncol, 2021, 10(1): 9. DOI: 10.21037/cco-20-89.
    [29]
    QUE J, WU HC, LIN CH, et al. Comparison of stereotactic body radiation therapy with and without sorafenib as treatment for hepatocellular carcinoma with portal vein tumor thrombosis[J]. Medicine (Baltimore), 2020, 99(13): e19660. DOI: 10.1097/MD.0000000000019660.
    [30]
    ZHAO X, SHAO C. Radiotherapy-mediated immunomodulation and anti-tumor abscopal effect combining immune checkpoint blockade[J]. Cancers (Basel), 2020, 12(10): 2762. DOI: 10.3390/cancers12102762.
    [31]
    ZERBINI A, PILLI M, LACCABUE D, et al. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response[J]. Gastroenterology, 2010, 138(5): 1931-1942. DOI: 10.1053/j.gastro.2009.12.051.
    [32]
    LENCIONI R, LLOVET JM, HAN GH, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate-stage HCC: The SPACE trial[J]. J Hepatol, 2016, 64(5): 1090-1098. DOI: 10.1016/j.jhep.2016.01.012.
    [33]
    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[J]. Gut, 2020, 69(8): 1492-1501. DOI: 10.1136/gutjnl-2019-318934.
    [34]
    DUFFY AG, ULAHANNAN SV, MAKOROVA-RUSHER O, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma[J]. J Hepatol, 2017, 66(3): 545-551. DOI: 10.1016/j.jhep.2016.10.029.
    [35]
    SANGRO B, GOMEZ-MARTIN C, de la MATA M, et al. A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C[J]. J Hepatol, 2013, 59(1): 81-88. DOI: 10.1016/j.jhep.2013.02.022.
    [36]
    PARIKH ND, WALJEE AK, SINGAL AG. Downstaging hepatocellular carcinoma: A systematic review and pooled analysis[J]. Liver Transpl, 2015, 21(9): 1142-1152. DOI: 10.1002/lt.24169.
    [37]
    SUN HC, ZHU XD, HUANG C, et al. Combination therapy with lenvatinib and anti-PD-1 antibodies for unresectable or advanced hepatocellular carcinoma: A real-world study[J]. J Clin Oncol, 2020, 38(Suppl. e1): 6610. http://www.researchgate.net/publication/341632504_Combination_therapy_with_lenvatinib_and_anti-PD-1_antibodies_for_unresectable_or_advanced_hepatocellular_carcinoma_A_real-world_study
    [38]
    CHAN SL, ZHU AX, FINN RS, et al. Effect of pembrolizumab (pembro) on hepatitis B viral (HBV) load and aminotransferase (ALT) levels in patients (pts) with advanced hepatocellular carcinoma (aHCC) in KEYNOTE-224 (KN224) and KEYNOTE-240 (KN240)[J]. J Clin Oncol, 2020, 38(Suppl): 4587.
    [39]
    SUN HC, ZHU XD, ZHOU J, et al. Effect of postoperative apatinib treatment after resection of hepatocellular carcinoma with portal vein invasion: A phase Ⅱ study[J]. J Clin Oncol, 2020, 38: 514. http://www.researchgate.net/publication/339038102_Effect_of_postoperative_apatinib_treatment_after_resection_of_hepatocellular_carcinoma_with_portal_vein_invasion_A_phase_II_study
    [40]
    KASEB A, DUDA D, CAO H, et al. Randomized, open-label, perioperative phase Ⅱ study evaluating nivolumab alone or nivolumab plus ipilimumab in patients with resectable HCC[J]. J Clin Oncol, 2020, 38: 486.
    [41]
    PINTER M, SCHEINER B, PECK-RADOSAVLJEVIC M. Immunotherapy for advanced hepatocellular carcinoma: A focus on special subgroups[J]. Gut, 2021, 70(1): 204-214. DOI: 10.1136/gutjnl-2020-321702.
    [42]
    SINN DH, CHOI GS, PARK HC, et al. Multidisciplinary approach is associated with improved survival of hepatocellular carcinoma patients[J]. PLoS One, 2019, 14(1): e0210730. DOI: 10.1371/journal.pone.0210730.
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