Onkologie. 2024:18(1):48-52 | DOI: 10.36290/xon.2024.010

Cholangiocellular carcinoma - treatment options

Marián Liberko, Renata Soumarová
Onkologická klinika, 3. LF UK a FNKV, Praha
3. lékařská fakulta Univerzity Karlovy, Praha

Cholangiocellular carcinoma represents major medical issue owing to its high mortality rate, despite not being frequent malignancy. Patients diagnosed at early stages are treated with postoperative treatment after surgery with the aim to decrease rate of locoregionanal or distant relapse. Nevertheless, majority of patients are diagnosed in locoregionaly advanced and/or metastatic stage. These patients are treated with systemic treatment. After years of stagnation there is proven survival benefit with the use of immunotherapy. Moreover, due to our better understanding of molecular biology of disease, we are able to better tailor treatment based on presence of targe­table alteration. We provide an overview of current treatment options for cholangiocarcinoma across stages.

Keywords: cholangiocellular carcinoma, NGS testing, systemic treatment, immunotherapy, targeted therapy.

Accepted: February 22, 2024; Published: February 28, 2024  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Liberko M, Soumarová R. Cholangiocellular carcinoma - treatment options. Onkologie. 2024;18(1):48-52. doi: 10.36290/xon.2024.010.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17(9):557-588. doi: 10.1038/s41575-020-0310-z. Epub 2020 Jun 30. PMID: 32606456; PMCID: PMC7447603. Go to original source... Go to PubMed...
    2. Vogel A, Bridgewater J, Edeline J, et al. Biliary tract can­cer: ESMO Clinical Practice Guideline for diagnosis, treat­ment and follow-up. Ann Oncol. 2023;34(2):127-140. doi: 10.1016/j.annonc.2022.10.506. Epub 2022 Nov 10. PMID: 36372281. Go to original source... Go to PubMed...
    3. Lamarca A, Barriuso J, McNamara MG, et al. Molecular targeted therapies: Ready for "prime time" in biliary tract cancer. J Hepatol. 2020;73(1):170-185. doi: 10.1016/j.jhep.2020.03.007. Epub 2020 Mar 12. PMID: 32171892. Go to original source... Go to PubMed...
    4. Kendre G, Murugesan K, Brummer T, et al. Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma. J Hepatol. 2023;78(3):614-626. doi: 10.1016/j.jhep.2022.11.030. Epub 2022 Dec 15. PMID: 36528236. Go to original source... Go to PubMed...
    5. Další literatura u autora a na www.onkologiecs.cz
    6. Tsilimigras DI, Sahara K, Wu L, et al. Very Early Recurrence After Liver Resection for Intrahepatic Cholangiocarcinoma: Considering Alternative Treatment Approaches. JAMA Surg. 2020;155(9):823-831. doi: 10.1001/jamasurg.2020.1973. PMID: 32639548; PMCID: PMC7344787. Go to original source... Go to PubMed...
    7. Ebata T, Hirano S, Konishi M, et al. Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer. Br J Surg. 2018;105(3):192-202. doi: 10.1002/bjs.10776. PMID: 29405274. Go to original source... Go to PubMed...
    8. Edeline J, Benabdelghani M, Bertaut A, et al. Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study. J Clin Oncol. 2019;37(8):658-667. doi: 10.1200/JCO.18.00050. Epub 2019 Feb 1. PMID: 30707660. Go to original source... Go to PubMed...
    9. Jeong H, Kim KP, Jeong JH, et al. Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial. Hepatology. 2023;77(5):1540-1549. doi: 10.1097/HEP.0000000000000046. Epub 2023 Jan 3. PMID: 37070950. Go to original source... Go to PubMed...
    10. Primrose JN, Fox RP, Palmer DH, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20(5):663-673. doi: 10.1016/S1470-2045(18)30915-X. Epub 2019 Mar 25. Erratum in: Lancet Oncol. 2019 Apr 2; PMID: 30922733. Go to original source... Go to PubMed...
    11. Bridgewater J, Fletcher P, Palmer DH, et al. Long-Term Outcomes and Exploratory Analyses of the Randomized Phase III BILCAP Study. J Clin Oncol. 2022;40(18):2048-2057. doi: 10.1200/JCO.21.02568. Epub 2022 Mar 22. PMID: 35316080. Go to original source... Go to PubMed...
    12. Nakachi K, Ikeda M, Konishi M, et al. Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2023;401(10372):195-203. doi: 10.1016/S0140-6736(22)02038-4. PMID: 36681415. Go to original source... Go to PubMed...
    13. Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al. SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma. J Clin Oncol. 2015;33(24):2617-2622. doi: 10.1200/JCO.2014.60.2219. Epub 2015 May 11. PMID: 25964250; PMCID: PMC4534524. Go to original source... Go to PubMed...
    14. Stein A, Arnold D, Bridgewater J, et al. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial. BMC Cancer. 2015;15:564. doi: 10.1186/s12885-015-1498-0. PMID: 26228433; PMCID: PMC4520064. Go to original source... Go to PubMed...
    15. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-1281. doi: 10.1056/NEJMoa0908721. PMID: 20375404. Go to original source... Go to PubMed...
    16. Phelip JM, Desrame J, Edeline J, et al. Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study. J Clin Oncol. 2022;40(3):262-271. doi: 10.1200/JCO.21.00679. Epub 2021 Oct 18. PMID: 34662180. Go to original source... Go to PubMed...
    17. Shroff RT, Javle MM, Xiao L, et al. Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA Oncol. 2019;5(6):824-830. doi: 10.1001/jamaoncol.2019.0270. PMID: 30998813; PMCID: PMC6567834. Go to original source... Go to PubMed...
    18. Rachna TS, Guthrie KA, Scott AJ, et al. SWOG 1815: A phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers. Journal of Clinical Oncology. 2023;41:4_suppl, LBA490. Go to original source...
    19. Sabbatino F, Villani V, Yearley JH, et al. PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma. Clin Cancer Res. 2016;22(2):470-478. doi: 10.1158/1078-0432.CCR-15-0715. Epub 2015 Sep 15. PMID: 26373575; PMCID: PMC5296951. Go to original source... Go to PubMed...
    20. Oh DY, Lee KH, Lee DW, et al. Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study. Lancet Gas­troenterol Hepatol. 2022;7(6):522-532. doi: 10.1016/S2468-1253(22)00043-7. Epub 2022 Mar 9. Erratum in: Lancet Gastro­enterol Hepatol. 2023 Jun;8(6):e5. PMID: 35278356. Go to original source... Go to PubMed...
    21. Oh DY, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2200015. Go to original source... Go to PubMed...
    22. Kelley RK, Ueno M, Yoo C, et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16. Erratum in: Lancet. 2023;402(10406):964. PMID: 37075781. Go to original source... Go to PubMed...
    23. 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. Lancet Oncol. 2021;22(5):690-701. doi: 10.1016/S1470-2045(21)00027-9. Epub 2021 Mar 30. PMID: 33798493; PMCID: PMC8082275. Go to original source... Go to PubMed...
    24. Hyung J, Kim I, Kim KP, et al. Treatment With Liposomal Irinotecan Plus Fluorouracil and Leucovorin for Patients With Previously Treated Metastatic Biliary Tract Cancer: The Phase 2b NIFTY Randomized Clinical Trial. JAMA Oncol. 2023;9(5):692-699. doi: 10.1001/jamaoncol.2023.0016. PMID: 36951834; PMCID: PMC10037199. Go to original source... Go to PubMed...
    25. Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(6):796-807. doi: 10.1016/S1470-2045(20)30157-1. Epub 2020 May 13. Erratum in: Lancet Oncol. 2020;21(10):e462. PMID: 32416072; PMCID: PMC7523268. Go to original source... Go to PubMed...
    26. Zhu AX, Macarulla T, Javle MM, et al. Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial. JAMA Oncol. 2021;7(11):1669-1677. doi: 10.1001/jamaoncol.2021.3836. PMID: 34554208; PMCID: PMC8461552. Go to original source... Go to PubMed...
    27. Lamarca A, Ostios L, McNamara MG, et al. Resistance mechanism to fibroblast growth factor receptor (FGFR) inhibitors in cholangiocarcinoma. Cancer Treat Rev. 2023;121:102627. doi: 10.1016/j.ctrv.2023.102627. Epub 2023 Sep 16. PMID: 37925878. Go to original source... Go to PubMed...
    28. Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21(5):671-684. doi: 10.1016/S1470-2045(20)30109-1. Epub 2020 Mar 20. Erratum in: Lancet Oncol. 2024;25(1):e3. PMID: 32203698; PMCID: PMC8461541. Go to original source... Go to PubMed...
    29. Javle M, Roychowdhury S, Kelley RK, et al. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol. 2021;6(10):803-815. doi: 10.1016/S2468-1253(21)00196-5. Epub 2021 Aug 3. PMID: 34358484. Go to original source... Go to PubMed...
    30. Goyal L, Meric-Bernstam F, Hollebecque A, et al. Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. N Engl J Med. 2023;388(3):228-239. doi: 10.1056/NEJMoa2206834. PMID: 36652354. Go to original source... Go to PubMed...
    31. Subbiah V, Sahai V, Maglic D, et al. RLY-4008, the First Highly Selective FGFR2 Inhibitor with Activity across FGFR2 Alterations and Resistance Mutations. Cancer Discov. 2023;13(9):2012-2031. doi: 10.1158/2159-8290.CD-23-0475. PMID: 37270847; PMCID: PMC10481131. Go to original source... Go to PubMed...
    32. Hollebecque A, Borad A, Goyal L. Efficacy of RLY-4008, a highly selective FGFR2 inhibitor in patients (pts) with an FGFR2-fusion or rearrangement (f/r), FGFR inhibitor (FGFRi)-naïve cholangiocarcinoma (CCA): ReFocus trial. Annals of Oncology. 2022;33(7): S1381. Available from: https://doi.org/10.1016/j.annonc.2022.08.006. Go to original source...
    33. Javle M, Kankeu Fonkoua LA, Mahipal A, et al. Tinengotinib in patients with advanced, fibroblast growth factor receptor (FGFR) inhibitor refractory/relapsed cholangiocarcinoma. Annals of Oncology. 2023;34(2):S215-S216. Available from: https://doi.org/10.1016/j.annonc.2023.09.1388. Go to original source...
    34. Subbiah V, Lassen U, Élez E, et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020;21(9):1234-1243. doi: 10.1016/S1470-2045(20)30321-1. Epub 2020 Aug 17. PMID: 32818466. Go to original source... Go to PubMed...
    35. Javle M, Borad MJ, Azad NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021;22(9):1290-1300. doi: 10.1016/S1470-2045(21)00336-3. Epub 2021 Jul 30. PMID: 34339623. Go to original source... Go to PubMed...
    36. Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial. J Clin Oncol. 2024;42(1):47-58. doi: 10.1200/JCO.23.02005. Epub 2023 Oct 23. PMID: 37870536; PMCID: PMC10730032. Go to original source... Go to PubMed...
    37. Harding JJ, Fan J, Oh DY, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol. 2023;24(7):772-782. doi: 10.1016/S1470-2045(23)00242-5. Epub 2023 Jun 2. PMID: 37276871. Go to original source... Go to PubMed...
    38. Marabelle A, Le DT, Ascierto PA, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020;38(1):1-10. doi: 10.1200/JCO.19.02105. Epub 2019 Nov 4. PMID: 31682550; PMCID: PMC8184060. Go to original source... Go to PubMed...

    Return to the content


    Oncology

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.