Journal of Surgery Concepts & Practice ›› 2025, Vol. 30 ›› Issue (06): 544-550.doi: 10.16139/j.1007-9610.2025.06.14
• Review • Previous Articles
YU Liqin, YAN Xiaoyu, WANG Puxiongzhi, WANG Wei(
), WANG Jian(
)
Received:2025-04-29
Online:2025-11-25
Published:2026-01-26
Contact:
WANG Wei, WANG Jian
E-mail:dr_wangjian@126.com;ww.wwj@163.com
CLC Number:
YU Liqin, YAN Xiaoyu, WANG Puxiongzhi, WANG Wei, WANG Jian. Current status and reflections on immunotherapy and targeted therapy for unresectable biliary tract cancer[J]. Journal of Surgery Concepts & Practice, 2025, 30(06): 544-550.
| [1] |
TARIQ N U, MCNAMARA M G, VALLE J W. Biliary tract cancers: current knowledge, clinical candidates and future challenges[J]. Cancer Manag Res, 2019, 11:2623-2642.
doi: 10.2147/CMAR URL |
| [2] |
VALLE J W, LAMARCA A, GOYAL L, et al. New horizons for precision medicine in biliary tract cancers[J]. Cancer Discov, 2017, 7(9):943-962.
doi: 10.1158/2159-8290.CD-17-0245 pmid: 28818953 |
| [3] |
BRANDI G, RIZZO A, DALL'OLIO F G, 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 URL |
| [4] |
ZHAO D Y, LIM K H. Current biologics for treatment of biliary tract cancers[J]. J Gastrointest Oncol, 2017, 8(3):430-440.
doi: 10.21037/jgo.2017.05.04 pmid: 28736630 |
| [5] |
KIM R D, CHUNG V, ALESE O B, et al. A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer[J]. JAMA Oncol, 2020, 6(6):888-894.
doi: 10.1001/jamaoncol.2020.0930 pmid: 32352498 |
| [6] |
PIHA-PAUL S A, OH D Y, UENO M, et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: results from the KEYNOTE-158 and KEYNOTE-028 studies[J]. Int J Cancer, 2020, 147(8):2190-2198.
doi: 10.1002/ijc.v147.8 URL |
| [7] |
UENO M, IKEDA M, MORIZANE C, et al. Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer: a non-randomised, multicentre, open-label, phase 1 study[J]. Lancet Gastroenterol Hepatol, 2019, 4(8):611-621.
doi: 10.1016/S2468-1253(19)30086-X URL |
| [8] |
HACK S P, ZHU A X. Atezolizumab: an investigational agent for the treatment of biliary tract cancer[J]. Expert Opin Investig Drugs, 2021, 30(10):1007-1015.
doi: 10.1080/13543784.2021.1974838 URL |
| [9] |
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: 10.21037/hbsn URL |
| [10] |
LEE S H, LEE H S, LEE S H, et al. Efficacy and safety of pembrolizumab for gemcitabine/cisplatin-refractory biliary tract cancer: a multicenter retrospective study[J]. J Clin Med, 2020, 9(6):1769.
doi: 10.3390/jcm9061769 URL |
| [11] | MARABELLE A, LE D T, ASCIERTO P A, 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]. J Clin Oncol, 2020, 38(1):1-10. |
| [12] |
SILVA V W, ASKAN G, DANIEL T D, et al. Biliary carcinomas: pathology and the role of DNA mismatch repair deficiency[J]. Chin Clin Oncol, 2016, 5(5):62.
doi: 10.21037/cco.2016.10.04 pmid: 27829276 |
| [13] |
MCNAMARA M G, JACOBS T, LAMARCA A, et al. Impact of high tumor mutational burden in solid tumors and challenges for biomarker application[J]. Cancer Treat Rev, 2020, 89:102084.
doi: 10.1016/j.ctrv.2020.102084 URL |
| [14] |
MARABELLE A, FAKIH M, LOPEZ J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study[J]. Lancet Oncol, 2020, 21(10):1353-1365.
doi: S1470-2045(20)30445-9 pmid: 32919526 |
| [15] | LI W, WANG Y, YU Y, et al. Toripalimab in advanced biliary tract cancer[J]. Innovation (Camb), 2022, 3(4):100255. |
| [16] | JEONG S Y, HONG J Y, PARK J O, et al. The efficacy of immune checkpoint inhibitors in biliary tract cancer with KRAS mutation[J]. Therap Adv Gastroenterol, 2023, 16:17562848231170484. |
| [17] |
CHEN X, WANG D, LIU J, et al. Genomic alterations in biliary tract cancer predict prognosis and immunotherapy outcomes[J]. J Immunother Cancer, 2021, 9(11):e003214.
doi: 10.1136/jitc-2021-003214 URL |
| [18] | OH D Y, RUTH HE A, QIN S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer[J]. NEJM Evid, 2022, 1(8):EVIDoa2200015. |
| [19] |
KELLEY R K, 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[J]. Lancet, 2023, 401(10391):1853-1865.
doi: 10.1016/S0140-6736(23)00727-4 pmid: 37075781 |
| [20] | OH D Y, HE A R, QIN S, et al. Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase Ⅲ TOPAZ-1 study[J]. J Hepatol,2025:S0168-8278(25)02201-9. |
| [21] |
CHEN X, WU X, WU H, et al. Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase Ⅱ trial[J]. J Immunother Cancer, 2020, 8(2):e001240.
doi: 10.1136/jitc-2020-001240 URL |
| [22] |
CHEN X, QIN S, GU S, et al. Camrelizumab plus oxaliplatin-based chemotherapy as first-line therapy for advanced biliary tract cancer: a multicenter, phase 2 trial[J]. Int J Cancer, 2021, 149(11):1944-1954.
doi: 10.1002/ijc.v149.11 URL |
| [23] |
MONGE C, PEHRSSON E C, XIE C, et al. A phase Ⅱ study of pembrolizumab in combination with capecitabine and oxaliplatin with molecular profiling in patients with advanced biliary tract carcinoma[J]. Oncologist, 2022, 27(3):e273-e285.
doi: 10.1093/oncolo/oyab073 URL |
| [24] |
KAAKOUR D, HAGOPIAN G, LEE S, et al. Durable responses in patients with advanced cholangiocarcinoma on sequential dual-agent immunotherapy after progressing on single-agent immunotherapy[J]. Am J Clin Oncol, 2022, 45(10):410-414.
doi: 10.1097/COC.0000000000000941 URL |
| [25] |
TEICHER B A. TGFβ-directed therapeutics: 2020[J]. Pharmacol Ther, 2021, 217:107666.
doi: 10.1016/j.pharmthera.2020.107666 URL |
| [26] |
YOO C, OH D Y, CHOI H J, et al. Phase Ⅰ study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract cancer[J]. J Immunother Cancer, 2020, 8(1):e000564.
doi: 10.1136/jitc-2020-000564 URL |
| [27] |
PILONES K A, VANPOUILLE-BOX C, DEMARIA S. Combination of radiotherapy and immune checkpoint inhibitors[J]. Semin Radiat Oncol, 2015, 25(1):28-33.
doi: 10.1016/j.semradonc.2014.07.004 pmid: 25481263 |
| [28] |
CHEN Y, WEI M, SHEN S, et al. The combination of radiation therapy and immunotherapy is effective and well-tolerated for unresectable biliary tract cancer[J]. Int J Radiat Oncol Biol Phys, 2022, 113(4):816-824.
doi: 10.1016/j.ijrobp.2022.03.019 URL |
| [29] |
VITALE L A, THOMAS L J, HE L Z, et al. Development of CDX-1140, an agonist CD40 antibody for cancer immunotherapy[J]. Cancer Immunol Immunother, 2019, 68(2):233-245.
doi: 10.1007/s00262-018-2267-0 pmid: 30382327 |
| [30] | KELLEY R K, MITCHELL E, BEHR S, et al. Phase 2 trial of pembrolizumab (PEM) plus granulocyte macrophage colony stimulating factor (GM-CSF) in advanced biliary cancers (ABC): clinical outcomes and biomarker analyses[J]. J Clin Oncol, 2018, 36(15_suppl):4087. |
| [31] |
KAM A E, MASOOD A, SHROFF R T. Current and emerging therapies for advanced biliary tract cancers[J]. Lancet Gastroenterol Hepatol, 2021, 6(11):956-969.
doi: 10.1016/S2468-1253(21)00171-0 URL |
| [32] |
SUTHERLAND M, AHMED O, ZAIDI A, et al. Current progress in systemic therapy for biliary tract cancers[J]. J Hepatobiliary Pancreat Sci, 2022, 29(10):1094-1107.
doi: 10.1002/jhbp.v29.10 URL |
| [33] |
ABOU-ALFA G K, SAHAI V, HOLLEBECQUE A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study[J]. Lancet Oncol, 2020, 21(5):671-684.
doi: 10.1016/S1470-2045(20)30109-1 URL |
| [34] |
JAVLE M, ROYCHOWDHURY S, KELLEY R K, 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[J]. Lancet Gastroenterol Hepatol, 2021, 6(10):803-815.
doi: 10.1016/S2468-1253(21)00196-5 URL |
| [35] |
GOYAL L, MERIC-BERNSTAM F, HOLLEBECQUE A, et al. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma[J]. N Engl J Med, 2023, 388(3):228-239.
doi: 10.1056/NEJMoa2206834 URL |
| [36] |
BEKAII-SAAB T S, VALLE J W, VAN CUTSEM E, et al. FIGHT-302: first-line pemigatinib vs. gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements[J]. Future Oncol, 2020, 16(30):2385-2399.
doi: 10.2217/fon-2020-0429 URL |
| [37] |
QUEIROZ M M, LIMA N F JR, BIACHI DE CASTRIA T. Immunotherapy and targeted therapy for advanced biliary tract cancer: adding new flavors to the pizza[J]. Cancers (Basel), 2023, 15(7):1970.
doi: 10.3390/cancers15071970 URL |
| [38] | SCHÖNHERR H, AYAZ P, TAYLOR A M, et al. Disco-very of lirafugratinib (RLY-4008), a highly selective irreversible small-molecule inhibitor of FGFR2[J]. Proc Natl Acad Sci U S A, 2024, 121(6):e2317756121. |
| [39] |
MOEINI A, SIA D, BARDEESY N, et al. Molecular pathogenesis and targeted therapies for intrahepatic cholangiocarcinoma[J]. Clin Cancer Res, 2016, 22(2):291-300.
doi: 10.1158/1078-0432.CCR-14-3296 pmid: 26405193 |
| [40] |
ABOU-ALFA G K, MACARULLA T, JAVLE M M, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study[J]. Lancet Oncol, 2020, 21(6):796-807.
doi: 10.1016/S1470-2045(20)30157-1 URL |
| [41] |
ZAREI M, HUE J J, HAJIHASSANI O, et al. Clinical development of IDH1 inhibitors for cancer therapy[J]. Cancer Treat Rev, 2022, 103:102334.
doi: 10.1016/j.ctrv.2021.102334 URL |
| [42] |
ARTEAGA C L, ENGELMAN J A. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics[J]. Cancer Cell, 2014, 25(3):282-303.
doi: 10.1016/j.ccr.2014.02.025 pmid: 24651011 |
| [43] |
TELLA S H, KOMMALAPATI A, BORAD M J, et al. Second-line therapies in advanced biliary tract cancers[J]. Lancet Oncol, 2020, 21(1):e29-e41.
doi: 10.1016/S1470-2045(19)30733-8 pmid: 31908303 |
| [44] |
VOGEL A, KASPER S, BITZER M, et al. PICCA study: panitumumab in combination with cisplatin/gemcitabine chemotherapy in KRAS wild-type patients with biliary cancer-a randomised biomarker-driven clinical phase Ⅱ AIO study[J]. Eur J Cancer, 2018, 92:11-19.
doi: 10.1016/j.ejca.2017.12.028 URL |
| [45] |
MALKA D, CERVERA P, FOULON S, et al. Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial[J]. Lancet Oncol, 2014, 15(8):819-828.
doi: 10.1016/S1470-2045(14)70212-8 pmid: 24852116 |
| [46] |
LEE J, PARK S H, CHANG H M, et al. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study[J]. Lancet Oncol, 2012, 13(2):181-188.
doi: 10.1016/S1470-2045(11)70301-1 pmid: 22192731 |
| [47] | BALASUBRAMANIAN B, YACQUB-USMAN K, VENKATRAMAN S, et al. Targeting FGFRs using PD173074 as a novel therapeutic strategy in cholangiocarcinoma[J]. Cancers(Basel), 2023, 15(9):2528. |
| [48] |
MORIZANE C, UENO M, IKEDA M, et al. Update for: new developments in systemic therapy for advanced biliary tract cancer[J]. Jpn J Clin Oncol, 2025, 55(3):210-218.
doi: 10.1093/jjco/hyaf016 pmid: 39902800 |
| [49] |
OSTWAL V, MANDAVKAR S, BHARGAVA P, et al. Trastuzumab plus gemcitabine-cisplatin for treatment-naïve human epidermal growth factor receptor 2-positive biliary tract adenocarcinoma: a multicenter, open-label, phase Ⅱ study (TAB)[J]. J Clin Oncol, 2024, 42(7):800-807.
doi: 10.1200/JCO.23.01193 URL |
| [50] |
LEE C K, CHON H J, CHEON J, et al. Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean cancer study group (KCSG-HB19-14)[J]. Lancet Gastroenterol Hepatol, 2023, 8(1):56-65.
doi: 10.1016/S2468-1253(22)00335-1 URL |
| [51] | NAKAMURA Y, MIZUNO N, SUNAKAWA Y, et al. Tucatinib and trastuzumab for previously treated human epidermal growth factor receptor 2-positive metastatic biliary tract cancer (SGNTUC-019): a phase Ⅱ basket study[J]. J Clin Oncol, 2023, 41(36):5569-5578. |
| [52] |
HARDING J J, FAN J, OH D Y, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study[J]. Lancet Oncol, 2023, 24(7):772-782.
doi: 10.1016/S1470-2045(23)00242-5 pmid: 37276871 |
| [53] |
OHBA A, MORIZANE C, KAWAMOTO Y, et al. Trastuzumab deruxtecan in human epidermal growth factor receptor 2-expressing biliary tract cancer (HERB; NCCH1805): a multicenter, single-arm, phase Ⅱ trial[J]. J Clin Oncol, 2024, 42(27):3207-3217.
doi: 10.1200/JCO.23.02010 URL |
| [54] | LI J, GUO Y, XUE J, et al. First-in-human phase Ⅰ study of anti-HER2 ADC MRG002 in patients with relapsed/refractory solid tumors[J]. J Clin Oncol, 2020,38(15_suppl):TPS1101-TPS1101(2020). |
| [55] |
PEI S N, LIAO C K, CHEN Y S, et al. A novel combination of bevacizumab with chemotherapy improves therapeutic effects for advanced biliary tract cancer: a retrospective, observational study[J]. Cancers (Basel), 2021, 13(15):3831.
doi: 10.3390/cancers13153831 URL |
| [56] |
MOFFAT G T, HU Z I, MERIC BERNSTAM F, et al. KRAS allelic variants in biliary tract cancers[J]. JAMA Netw Open, 2024, 7(5):e249840.
doi: 10.1001/jamanetworkopen.2024.9840 URL |
| [57] | BEKAII SAAB T S, YAEGER R, SPIRA A I, et al. Adagrasib in advanced solid tumors harboring a KRASG12C mutation[J]. J Clin Oncol, 2023, 41(25):4097-4106. |
| [58] |
HO J, FIOCCO C, SPENCER K. Treating biliary tract cancers: new targets and therapies[J]. Drugs, 2022, 82(17):1629-1647.
doi: 10.1007/s40265-022-01808-x |
| [59] |
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[J]. Lancet Oncol, 2020, 21(9):1234-1243.
doi: 10.1016/S1470-2045(20)30321-1 URL |
| [60] |
MIYAMOTO M, OJIMA H, IWASAKI M, et al. Prognostic significance of overexpression of c-Met oncoprotein in cholangiocarcinoma[J]. Br J Cancer, 2011, 105(1):131-138.
doi: 10.1038/bjc.2011.199 |
| [61] |
WANG Y, JIANG M, ZHU J, et al. The safety and efficacy of lenvatinib combined with immune checkpoint inhibitors therapy for advanced hepatocellular carcinoma[J]. Biomed Pharmacother, 2020, 132:110797.
doi: 10.1016/j.biopha.2020.110797 pmid: 33068935 |
| [62] |
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 URL |
| [63] |
WANG D, YANG X, LONG J, et al. The efficacy and safety of apatinib plus camrelizumab in patients with previously treated advanced biliary tract cancer: a prospective clinical study[J]. Front Oncol, 2021, 11:646979.
doi: 10.3389/fonc.2021.646979 URL |
| [64] |
FOUASSIER L, MARZIONI M, AFONSO M B, et al. Signalling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance[J]. Liver Int, 2019, 39(Suppl 1):43-62.
doi: 10.1111/liv.2019.39.issue-S1 URL |
| [65] | YOKOI K, KOBAYASHI A, MOTOYAMA H, et al. Survival pathway of cholangiocarcinoma via AKT/mTOR signaling to escape RAF/MEK/ERK pathway inhibition by sorafenib[J]. Oncol Rep, 2018, 39(2):843-850. |
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