中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 8
Aug.  2022
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(8): 1813-1818

Efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for intrahepatic cholangiocarcinoma

DOI: 10.3969/j.issn.1001-5256.2022.08.018

  • Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China

Research funding:

Foundation of Capital Distinctive Clinical Application Research (Z181100001718131)

More Information
  • Corresponding author: CHEN Jinglong, cjl6412@ccmu.edu.cn(ORCID: 0000-0003-1640-7115)
  • Received Date: 2022-01-28
  • Accepted Date: 2022-03-15
  • Published Date: 2022-08-20
    Abstract
  •   Objective  To investigate the efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for advanced intrahepatic cholangiocarcinoma (ICC).  Methods  A retrospective analysis was performed for the clinical data of the patients with advanced ICC who were admitted to Beijing Ditan Hospital from October 31, 2019 to October 31, 2021 and could not undergo surgery or experienced metastasis after surgery. All patients were treated with lenvatinib combined with sintilimab as the second-line therapy. The patients were followed up, and the RECIST1.1 criteria were used to assess treatment outcome. The primary endpoint was time to progression (TTP), and the secondary endpoints were tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS) time, and safety. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups.  Results  A total of 27 patients were enrolled, among whom there were15 male patients (55.6%) and 12 female patients (44.4%), with a median age of 58 years (range 33-73 years). The median TTP for these patients was 5.5 (95% confidence interval [CI]: 1.7-9.3) months, and 13 patients (48.1%) died of disease progression, with a median OS time of 11.2 (95%CI: 5.0-17.4) months. The overall ORR and DCR were 40.7% and 70.3%, respectively. Of all patients, 66.7% experienced varying degrees of adverse events, and among these patients, 44.4% had an increase in alanine aminotransferase, 44.4% had an increase in aspartate aminotransferase, 37.0% had hypertension, 29.6% had an increase in bilirubin, 29.6% experienced diarrhea, and 25.9% each experienced proteinuria, anorexia, and weakness. No treatment-related death was observed, and only 1 patient developed grade Ⅳ immune-related hepatotoxicity and was relieved without sequelae after corticosteroid therapy, resulting in permanent withdrawal of sintilimab. The patients with lymph node metastasis had a significantly shorter median TTP than those without lymph node metastasis (4.5 months vs 18.8 months, P=0.035), and the patients who achieved disease remission had a significantly longer median TTP [11.6 months (95%CI: 5.6-17.6) vs 2.8 months (95%CI: 1.8-3.8), P < 0.001]; the patients with lymph node metastasis had a shorter median OS time [9.6 months (95%CI: 7.9-11.3) vs 21.9 months (95%CI: 0-44.9), P=0.053], and the patients who achieved disease remission had a significantly longer median OS time [16.6 months (95%CI: 9.0-24.2) vs 6.9 months (95%CI: 3.6-10.2), P=0.011].  Conclusion  Lenvatinib combined with sintilimab has a marked clinical effect and a low incidence rate of serious adverse events as the second-line therapy for advanced ICC, and therefore, it is a safe and effective treatment regimen.

     

    • FullText(HTML)
  • loading
    • References(23)
  • [1]
    KHAN SA, TAVOLARI S, BRANDI G. Cholangiocarcinoma: Epidemiology and risk factors[J]. Liver Int, 2019, 39 (Suppl 1): 19-31. DOI: 10.1111/liv.14095.
    [2]
    BERTUCCIO P, MALVEZZI M, CARIOLI G, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma[J]. J Hepatol, 2019, 71(1): 104-114. DOI: 10.1016/j.jhep.2019.03.013.
    [3]
    SQUADRONI M, TONDULLI L, GATTA G, et al. Cholangiocarcinoma[J]. Crit Rev Oncol Hematol, 2017, 116: 11-31. DOI: 10.1016/j.critrevonc.2016.11.012.
    [4]
    VALLE J, WASAN H, PALMER DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer[J]. N Engl J Med, 2010, 362(14): 1273-1281. DOI: 10.1056/NEJMoa0908721.
    [5]
    VALLE JW, FURUSE J, JITLAL M, et al. Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials[J]. Ann Oncol, 2014, 25(2): 391-398. DOI: 10.1093/annonc/mdt540.
    [6]
    LAMARCA A, PALMER DH, WASAN HS, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial[J]. Lancet Oncol, 2021, 22(5): 690-701. DOI: 10.1016/S1470-2045(21)00027-9.
    [7]
    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.
    [8]
    KUDO M, IKEDA M, MOTOMURA K, et al. A phase Ib study of lenvatinib (LEN) plus nivolumab (NⅣ) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Study 117[J]. J Clin Oncol, 2020, 38(4_suppl): 513. DOI: 10.1200/JCO.2020.38.4_suppl.513.
    [9]
    LEE AJ, CHUN YS. Intrahepatic cholangiocarcinoma: the AJCC/UICC 8th edition updates[J]. Chin Clin Oncol, 2018, 7(5): 52. DOI: 10.21037/cco.2018.07.03.
    [10]
    MAKAR AB, MCMARTIN KE, PALESE M, et al. Formate assay in body fluids: application in methanol poisoning[J]. Biochem Med, 1975, 13(2): 117-126. DOI: 10.1016/0006-2944(75)90147-7.
    [11]
    BRANDI G, RIZZO A, DALL'OLIO FG, et al. Percutaneous radiofrequency ablation in intrahepatic cholangiocarcinoma: a retrospective single-center experience[J]. Int J Hyperthermia, 2020, 37(1): 479-485. DOI: 10.1080/02656736.2020.1763484.
    [12]
    YOSHIKAWA D, OJIMA H, IWASAKI M, et al. Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma[J]. Br J Cancer, 2008, 98(2): 418-425. DOI: 10.1038/sj.bjc.6604129.
    [13]
    XU YF, YANG XQ, LU XF, et al. Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma[J]. Biochem Biophys Res Commun, 2014, 446(1): 54-60. DOI: 10.1016/j.bbrc.2014.02.050.
    [14]
    BOONJARASPINYO S, BOONMARS T, WU Z, et al. Platelet-derived growth factor may be a potential diagnostic and prognostic marker for cholangiocarcinoma[J]. Tumour Biol, 2012, 33(5): 1785-1802. DOI: 10.1007/s13277-012-0438-8.
    [15]
    TOHYAMA O, MATSUI J, KODAMA K, et al. Antitumor activity of lenvatinib (e7080): an angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models[J]. J Thyroid Res, 2014, 2014: 638747. DOI: 10.1155/2014/638747.
    [16]
    KIMURA T, KATO Y, OZAWA Y, et al. Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1-6 hepatocellular carcinoma model[J]. Cancer Sci, 2018, 109(12): 3993-4002. DOI: 10.1111/cas.13806.
    [17]
    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.
    [18]
    UENO M, IKEDA M, SASAKI T, et al. Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results[J]. BMC Cancer, 2020, 20(1): 1105. DOI: 10.1186/s12885-020-07365-4.
    [19]
    O'MALLEY DM, BARIANI GM, CASSIER PA, et al. Pembrolizumab in patients with microsatellite instability-high advanced endometrial cancer: results from the KEYNOTE-158 study[J]. J Clin Oncol, 2022, 40(7): 752-761. DOI: 10.1200/JCO.21.01874.
    [20]
    KIM RD, KIM DW, ALESE OB, et al. A phase lI study of nivolumab in patients with advanced refractory biliary tract cancers (BTC)[J]. J Clin Oncol, 2019, 37(15_suppl): 4097. DOI: 10.1200/JCO.2019.37.15_suppl.4097.
    [21]
    LIN J, YANG X, LONG J, et al. Pembrolizumab combined with lenvatinib as non-first-line therapy in patients with refractory biliary tract carcinoma[J]. Hepatobiliary Surg Nutr, 2020, 9(4): 414-424. DOI: 0.21037/bsn-20-338.
    [22]
    KATO Y, TABATA K, KIMURA T, et al. Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway[J]. PLoS One, 2019, 14(2): e0212513. DOI: 10.1371/journal.pone.0212513.
    [23]
    ZHANG Q, LIU X, WEI S, et al. Lenvatinib plus PD-1 inhibitors as first-line treatment in patients with unresectable biliary tract cancer: A single-arm, open-label, phase ii study[J]. Front Oncol, 2021, 11: 751391. DOI: 10.3389/fonc.2021.751391.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(3)  / Tables(2)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (1274) PDF downloads(123) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return