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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 40 Issue 10
Oct.  2024
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Article Contents

Efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with advanced hepatocellular carcinoma

DOI: 10.12449/JCH241017
Research funding:

National Natural Science Foundation of China (82170626);

Natural Science Foundation of Shaanxi Province (2022SF-451);

Capital Health Development Research Special Project (2024-2-2176)

More Information
  • Corresponding author: GUO Jiang, guojiang7606@ccmu.edu.cn (ORCID: 0000-0001-8297-5458); GAO Ning, gaohuining1@163.com (ORCID: 0000-0003-1018-3990)
  • Received Date: 2024-01-22
  • Accepted Date: 2024-04-29
  • Published Date: 2024-10-25
  •   Objective  To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma (HCC).  Methods  A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1, 2019 to March 31, 2021, and all patients received camrelizumab monoclonal antibody treatment, among whom 84.8% also received targeted therapy. According to the age of the patients, they were divided into elderly group (≥65 years) and non-elderly group (<65 years). The two groups were assessed in terms of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and immune-related adverse events (irAE). The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups; the independent samples t-test was used for comparison of normally distributed continuous data, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.  Results  A total of 99 HCC patients were enrolled, with 27 in the elderly group and 72 in the non-elderly group. The elderly group had an OS rate of 67.8%, an ORR of 44.4%, and a DCR of 74.1% at 12 months and a median PFS of 6.4 (95% confidence interval [CI]: 3.0‍ ‍—‍ ‍12.4) months, with no significant differences compared with the non-elderly group (all P>0.05). The median OS was unavailable for the elderly group, while the non-elderly group had an OS of 18.9 (95%CI: 13.0‍ ‍—‍ ‍24.8) months; there was no significant difference between the two groups (P=0.485). The univariate and multivariate Cox regression analyses showed that major vascular invasion (MVI) was an independent risk factor for PFS (hazard ratio [HR]=2.603, 95%CI: 1.136‍ ‍—‍ ‍5.964, P=0.024) and DCR (HR=3.963, 95%CI: 1.671‍ ‍—‍ ‍9.397, P=0.002) at 6 months, while age, sex, etiology of HBV infection, presence of extrahepatic metastasis, Child-Pugh class B, and alpha-fetoprotein>400 ng/mL were not associated with PFS or DCR at 6 months. For the elderly group, the incidence rates of any irAE and grade 3/4 irAE were 51.9% and 25.9%, respectively, with no significant differences compared with the non-elderly group (P>0.05), and skin disease was the most common irAE in both groups (39.4%).  Conclusion  Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged ≥65 years and those aged <65 years. MVI is associated with suboptimal response to immunotherapy and poor prognosis.

     

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  • [1]
    YANG JD, HAINAUT P, GORES GJ, et al. A global view of hepatocellular carcinoma: Trends, risk, prevention and management[J]. Nat Rev Gastroenterol Hepatol, 2019, 16( 10): 589- 604. DOI: 10.1038/s41575-019-0186-y.
    [2]
    RUMGAY H, ARNOLD M, FERLAY J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040[J]. J Hepatol, 2022, 77( 6): 1598- 1606. DOI: 10.1016/j.jhep.2022.08.021.
    [3]
    SMITH BD, SMITH GL, HURRIA A, et al. Future of cancer incidence in the United States: Burdens upon an aging, changing nation[J]. J Clin Oncol, 2009, 27( 17): 2758- 2765. DOI: 10.1200/JCO.2008.20.8983.
    [4]
    LLOVET JM, KELLEY RK, VILLANUEVA A, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2021, 7: 6. DOI: 10.1038/s41572-020-00240-3.
    [5]
    LIU JH, CHEN ZC, LI YQ, et al. PD-1/PD-L1 checkpoint inhibitors in tumor immunotherapy[J]. Front Pharmacol, 2021, 12: 731798. DOI: 10.3389/fphar.2021.731798.
    [6]
    RAO Q, LI M, XU W, et al. Clinical benefits of PD-1/PD-L1 inhibitors in advanced hepatocellular carcinoma: A systematic review and meta-analysis[J]. Hepatol Int, 2020, 14( 5): 765- 775. DOI: 10.1007/s12072-020-10064-8.
    [7]
    WANG Y, JIANG M, ZHU JJ, et al. The safety and efficacy of lenvatinib combined with immune checkpoint inhibitors therapy for advanced hepatocellular carcinoma[J]. Biomedecine Pharmacother, 2020, 132: 110797. DOI: 10.1016/j.biopha.2020.110797.
    [8]
    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.
    [9]
    OMATA M, CHENG AL, KOKUDO N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: A 2017 update[J]. Hepatol Int, 2017, 11( 4): 317- 370. DOI: 10.1007/s12072-017-9799-9.
    [10]
    LI T, GUO J, LIU YS, et al. Effectiveness and tolerability of camrelizumab combined with molecular targeted therapy for patients with unresectable or advanced HCC[J]. Cancer Immunol Immunother, 2023, 72( 7): 2137- 2149. DOI: 10.1007/s00262-023-03404-8.
    [11]
    LLOVET JM, LENCIONI R. mRECIST for HCC: Performance and novel refinements[J]. J Hepatol, 2020, 72( 2): 288- 306. DOI: 10.1016/j.jhep.2019.09.026.
    [12]
    MEI KM, QIN SK, CHEN ZD, et al. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: Cohort A report in a multicenter phase Ib/II trial[J]. J Immunother Cancer, 2021, 9( 3): e002191. DOI: 10.1136/jitc-2020-002191.
    [13]
    CAI JQ, ZHANG BL, BI XY. Comprehensive treatment strategy for hepatocellular carcinoma based on surgical treatment in the era of targeted therapy and immunotherapy[J]. Chin J Dig Surg, 2023, 22( 2): 181- 186. DOI: 10.3760/cma.j.cn115610-20221130-0071.

    蔡建强, 张搏伦, 毕新宇. 靶向联合免疫治疗时代以外科为主的肝细胞癌综合治疗策略[J]. 中华消化外科杂志, 2023, 22( 2): 181- 186. DOI: 10.3760/cma.j.cn115610-20221130-00719.
    [14]
    LI H, QIN SK, LIU Y, et al. Camrelizumab combined with FOLFOX4 regimen as first-line therapy for advanced hepatocellular carcinomas: A sub-cohort of a multicenter phase ib/II study[J]. Drug Des Devel Ther, 2021, 15: 1873- 1882. DOI: 10.2147/DDDT.S304857.
    [15]
    YUAN GS, CHENG X, LI Q, et al. Safety and efficacy of camrelizumab combined with apatinib for advanced hepatocellular carcinoma with portal vein tumor Thrombus: A multicenter retrospective study[J]. Onco Targets Ther, 2020, 13: 12683- 12693. DOI: 10.2147/OTT.S286169.
    [16]
    QIN SK, REN ZG, MENG ZQ, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: A multicentre, open-label, parallel-group, randomised, phase 2 trial[J]. Lancet Oncol, 2020, 21( 4): 571- 580. DOI: 10.1016/S1470-2045(20)30011-5.
    [17]
    XU JM, SHEN J, GU SZ, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma(RESCUE): A nonrandomized, open-label, phase II trial[J]. Clin Cancer Res, 2021, 27( 4): 1003- 1011. DOI: 10.1158/1078-0432.CCR-20-2571.
    [18]
    VITHAYATHIL M, D’ALESSIO A, FULGENZI CAM, et al. Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma[J]. Liver Int, 2022, 42( 11): 2538- 2547. DOI: 10.1111/liv.15405.
    [19]
    TADA T, KUMADA T, HIRAOKA A, et al. Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: A multicenter analysis[J]. Cancer Med, 2022, 11( 20): 3796- 3808. DOI: 10.1002/cam4.4763.
    [20]
    BORZIO M, DIONIGI E, VITALE A, et al. Management and prognosis of hepatocellular carcinoma in the elderly: Results of an in-field multicenter cohort study[J]. Liver Int, 2017, 37( 8): 1184- 1192. DOI: 10.1111/liv.13392.
    [21]
    GUO H, WU T, LU Q, et al. Hepatocellular carcinoma in elderly: Clinical characteristics, treatments and outcomes compared with younger adults[J]. PLoS One, 2017, 12( 9): e0184160. DOI: 10.1371/journal.pone.0184160.
    [22]
    DELIGIORGI MV, TRAFALIS DT. Reversible primary adrenal insufficiency related to anti-programmed cell-death 1 protein active immunotherapy: Insight into an unforeseen outcome of a rare immune-related adverse event[J]. Int Immunopharmacol, 2020, 89( Pt B): 107050. DOI: 10.1016/j.intimp.2020.107050.
    [23]
    ZHANG Y, ZHANG X, LI W, et al. Biomarkers and risk factors for the early prediction of immune-related adverse events: a review[J]. Hum Vaccin Immunother, 2022, 18( 1): 2018894. DOI: 10.1080/21645515.2021.2018894.
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