664
Views
16
CrossRef citations to date
0
Altmetric
Review

Targeting FGFR in intrahepatic cholangiocarcinoma [iCCA]: leading the way for precision medicine in biliary tract cancer [BTC]?

, & ORCID Icon
Pages 463-477 | Received 21 Dec 2020, Accepted 05 Mar 2021, Published online: 11 Apr 2021

References

  • Marin JJG, Prete MG, Lamarca A, et al. Current and novel therapeutic opportunities for systemic therapy in biliary cancer. Br J Cancer. 2020;123(7):1047–1059.
  • Altekruse SF, Petrick JL, Rolin AI, et al. Geographic variation of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and hepatocellular carcinoma in the United States. PLoS One. 2015;10(3):e0120574.
  • Saha SK, Zhu AX, Fuchs CS, et al. Forty-Year Trends in Cholangiocarcinoma Incidence in the U.S.: intrahepatic Disease on the Rise. Oncologist. 2016;21(5):594–599.
  • Bertuccio P, Malvezzi M, Carioli G, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 2019;71(1):104–114.
  • Everhart JE, Ruhl CE. Burden of digestive diseases in the United States Part III: liver, biliary tract, and pancreas. Gastroenterology. 2009;136(4):1134–1144.
  • Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2017. Bethesda, MD: National Cancer Institute; 2020 April. https://seer.cancer.gov/csr/1975_2017/, based on November 2019 SEER data submission, posted to the SEER web site. Last accessed November 20, 2020.
  • El-Diwany R, Pawlik TM, Ejaz A. Intrahepatic Cholangiocarcinoma. Surg Oncol Clin N Am. 2019;28(4):587–599.
  • Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268–1289.
  • Sapisochin G, Rodríguez De Lope C, Gastaca M, et al. “Very early” intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients? Am J Transplant. 2014;14(3):660–667.
  • Sapisochin G, Facciuto M, Rubbia-Brandt L, et al. Liver transplantation for “very early” intrahepatic cholangiocarcinoma: international retrospective study supporting a prospective assessment. Hepatology. 2016;64(4):1178–1188.
  • 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.
  • Lamarca A, Ross P, Wasan HS, et al. Advanced intrahepatic cholangiocarcinoma: post hoc analysis of the ABC-01, −02, and −03 Clinical Trials. J Natl Cancer Inst. 2020;112(2):200–210.
  • Okusaka T, Nakachi K, Fukutomi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010;103(4):469–474.
  • Lamarca A, Palmer DH, Wasan HS, et al. A randomised phase III, multi-centre, open-label study of Active Symptom Control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced/metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. [abstract ABC-06]. J Clin Oncol. 2019;37(5_suppl. 15):4003
  • Jiao Y, Pawlik TM, Anders RA, et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet. 2013;45(12):1470–1473.
  • Sia D, Losic B, Moeini A, et al. Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma. Nat Commun. 2015;6:6087. Published 2015 Jan 22.
  • Ross JS, Wang K, Gay L, et al. New routes to targeted therapy of intrahepatic cholangiocarcinomas revealed by next-generation sequencing. Oncologist. 2014;19(3):235–242.
  • Lamarca A, Kapacee Z, Breeze M, et al. molecular profiling in daily clinical practice: practicalities in advanced cholangiocarcinoma and other biliary tract cancers. J Clin Med. 2020;9(9):2854.
  • Nakamura H, Arai Y, Totoki Y, et al. Genomic spectra of biliary tract cancer. Nat Genet. 2015;47(9):1003–1010.
  • TCGA Research Network. Genomic Data Commons Data Portal. [cited 2020 Nov 23]. Available from: https://portal.gdc.cancer.gov/exploration?facetTab=clinical&filters=%7B%22op%22%3A%22and%22%2C%22content%22%3A%5B%7B%22op%22%3A%22in%22%2C%22content%22%3A%7B%22field%22%3A%22cases.diagnoses.primary_diagnosis%22%2C%22value%22%3A%5B%22cholangiocarcinoma%22%5D%7D%7D%2C%7B%22op%22%3A%22in%22%2C%22content%22%3A%7B%22field%22%3A%22cases.project.project_id%22%2C%22value%22%3A%5B%22TCGA-CHOL%22%5D%7D%7D%2C%7B%22op%22%3A%22in%22%2C%22content%22%3A%7B%22field%22%3A%22genes.is_cancer_gene_census%22%2C%22value%22%3A%5B%22true%22%5D%7D%7D%5D%7D&searchTableTab=genes.
  • Churi CR, Shroff R, Wang Y, et al. Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications. PLoS One. 2014;9(12):e115383.
  • Zhu AX, Borger DR, Kim Y, et al. Genomic profiling of intrahepatic cholangiocarcinoma: refining prognosis and identifying therapeutic targets. Ann Surg Oncol. 2014;21(12):3827–3834.
  • Lowery MA, Ptashkin R, Jordan E, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res. 2018;24(17):4154–4161.
  • Wang P, Dong Q, Zhang C, et al. Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Oncogene. 2013 Jun 20;32(25):3091–3100.
  • Saha SK, Parachoniak CA, Ghanta KS, et al. Corrigendum: mutant IDH inhibits HNF-4alpha to block hepatocyte differentiation and promote biliary cancer. Nature. 2015 Dec 3;528(7580):152.
  • Mahipal A, Kommalapati A, Tella SH, et al. Novel targeted treatment options for advanced cholangiocarcinoma. Expert Opin Investig Drugs. 2018;27(9):709–720.
  • Masclef L, Ahmed O, Estavoyer B, et al. Roles and mechanisms of BAP1 deubiquitinase in tumor suppression. Cell Death Differ. 2021;28(2):606–625
  • Kongpetch S, Jusakul A, Ong CK, et al. Pathogenesis of cholangiocarcinoma: from genetics to signalling pathways. Best Pract Res Clin Gastroenterol. 2015;29(2):233–244.
  • Wu Y-M, Su F, Kalyana-Sundaram S, et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov. 2013;3:636–647.
  • Arai Y, Totoki Y, Hosoda F, et al. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma. Hepatology. 2014;59(4):1427–1434.
  • Graham RP, Barr Fritcher EG, Pestova E, et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol. 2014;45(8):1630–1638.
  • Moeini A, Sia D, Bardeesy N, et al. Molecular pathogenesis and targeted therapies for intrahepatic cholangiocarcinoma. Clin Cancer Res. 2016;22(2):291–300.
  • Zhang M, Yang H, Wan L, et al. Single-cell transcriptomic architecture and intercellular crosstalk of human intrahepatic cholangiocarcinoma. J Hepatol. 2020;73(5):1118–1130.
  • Wang F, Kan M, Xu J, et al. Ligand-specific structural domains in the fibroblast growth factor receptor. J Biol Chem. 1995;270(17):10222–10230.
  • Farrell B, Breeze AL. Structure, activation and dysregulation of fibroblast growth factor receptor kinases: perspectives for clinical targeting. Biochem Soc Trans. 2018;46(6):1753–1770.
  • Mohammadi M, Olsen SK, Ibrahimi OA. Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev. 2005;16:107–137.
  • Kalinina J, Dutta K, Ilghari D, et al. The alternatively spliced acid box region plays a key role in FGF receptor autoinhibition. Structure. 2012;20:77–88.
  • Dai S, Zhou Z, Chen Z, et al. Fibroblast growth factor receptors (FGFRs): structures and small molecule inhibitors. Cells. 2019;8(6):614.
  • Guimarães CR, Rai BK, Munchhof MJ, et al. Understanding the impact of the P-loop conformation on kinase selectivity. J Chem Inf Model. 2011;51(6):1199–1204.
  • Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117–1134.
  • Katoh M, Nakagama H. FGF receptors: cancer biology and therapeutics. Med Res Rev. 2014;34(2):280–300.
  • Ornitz DM, Itoh N. The Fibroblast Growth Factor signaling pathway. Wiley Interdiscip Rev Dev Biol. 2015;4(3):215–266.
  • Chen H, Marsiglia WM, Cho MK, et al. Elucidation of a four-site allosteric network in fibroblast growth factor receptor tyrosine kinases. Elife. 2017;6:e21137. Published 2017 Feb 6
  • Katoh M. Fibroblast growth factor receptors as treatment targets in clinical oncology. Nat Rev Clin Oncol. 2019;16(2):105–122.
  • Farshidfar F, Zheng S, Gingras MC, et al. Integrative genomic analysis of cholangiocarcinoma identifies distinct IDH-mutant molecular profiles [published correction appears in cell rep. 2017 Jun 27;19(13):2878-2880]. Cell Rep. 2017;18(11):2780–2794.
  • Javle M, Lowery M, Shroff RT, et al. Phase II study of bgj398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 2018;36(3):276–282.
  • Shin E, Lim DH, Han J, et al. Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors. BMC Ophthalmol. 2020;20:19.
  • 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.
  • Silverman IM, Hollebecque A, Friboulet L, et al. Clinicogenomic analysis of FGFR2-rearranged cholangiocarcinoma identifies correlates of response and mechanisms of resistance to pemigatinib. Cancer Discov. 2021;11(2):326–339.
  • Goyal L, Saha SK, Liu LY, et al. Polyclonal secondary FGFR2 mutations drive acquired resistance to FGFR inhibition in patients with FGFR2 fusion-positive cholangiocarcinoma. Cancer Discov. 2017;7:252–263.
  • Goyal L, Shi L, Liu LY, et al. TAS-120 overcomes resistance to ATP-competitive FGFR inhibitors in patients with FGFR2 fusion-positive intrahepatic cholangiocarcinoma. Cancer Discov. 2019;9:1064–1079.
  • Krook MA, Bonneville R, Chen HZ, et al. Tumor heterogeneity and acquired drug resistance in FGFR2-fusion-positive cholangiocarcinoma through rapid research autopsy. Cold Spring Harb Mol Case Stud. 2019;5:a004002.
  • Chen H, Ma J, Li W, et al. A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases. Mol Cell. 2007;27:717–730.
  • Huang Z, Chen H, Blais S, et al. Structural mimicry of a-loop tyrosine phosphorylation by a pathogenic FGF receptor 3 mutation. Structure. 2013;21:1889–1896.
  • U.S. Food and Drug Administration. Center for Drug Evaluation and Research. “FDA grants accelerated approval to pemigatinib for cholangiocarcinoma with an FGFR2 rearrangement or fusion.” U.S. FDA, 17 April 2020. [cited 2020 Nov 21]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pemigatinib-cholangiocarcinoma-fgfr2-rearrangement-or-fusion
  • Goyal L, Meric-Bernstam F, Hollebecque A, et al. FOENIX-CCA2: a phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements. J Clin Oncol. 2020;38(5_suppl. 15):108.
  • Furuse J, Goyal L, Meric-Bernstam F, et al. Efficacy, safety, and quality of life (QoL) with futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements: FOENIX-CCA2. Ann Oncol. 2020;31(suppl_6):S1287–S1318.
  • Mazzaferro V, El-Rayes BF, Droz Dit Busset M, et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019;120(2):165–171.
  • Park JO, Feng Y, Chen Y, et al. Updated results of a phase IIa study to evaluate the clinical efficacy and safety of erdafitinib in Asian advanced cholangiocarcinoma (CCA) patients with FGFR alterations. J Clin Oncol. 2019;37(5_suppl. 15):4117.
  • Bahleda R, Italiano A, Hierro C, et al. Multicenter phase i study of Erdafitinib (JNJ-42756493), oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced or refractory solid tumors. Clin Cancer Res. 2019;25(16):4888–4897.
  • Voss MH, Hierro C, Heist RS, et al. A phase I, open-label, multicenter, dose-escalation study of the oral selective FGFR inhibitor debio 1347 in patients with advanced solid tumors harboring FGFR gene alterations. Clin Cancer Res. 2019;25:2699–2707.
  • Ng MCH, Goyal L, Bang YJ, et al. AB065. P-36. Debio 1347 in patients with cholangiocarcinoma harboring an FGFR gene alteration: preliminary results. Hepatobiliary Surg Nutr. 2019;8(Suppl. 1):AB065.
  • Wu D, Guo M, Min X, et al. LY2874455 potently inhibits FGFR gatekeeper mutants and overcomes mutation-based resistance. Chem Commun (Camb). 2018;54:12089–12092.
  • Michael M, Bang YJ, Park YS, et al. A phase 1 study of LY2874455, an oral selective pan-FGFR inhibitor, in patients with advanced cancer. Target Oncol. 2017;12(4):463–474.
  • Chae YK, Hong F, Vaklavas C, et al. Phase II study of AZD4547 in patients with tumors harboring aberrations in the FGFR pathway: results from the NCI-MATCH Trial (EAY131) Subprotocol W. J Clin Oncol. 2020;38(21):2407–2417.
  • Saborowski A, Lehmann U, Vogel A. FGFR inhibitors in cholangiocarcinoma: what’s now and what’s next? Ther Adv Med Oncol. 2020 Published 2020 Sep 16;12:1758835920953293.
  • 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.
  • Delahousse J, Verlingue L, Broutin S, et al. Circulating oncometabolite D-2-hydroxyglutarate enantiomer is a surrogate marker of isocitrate dehydrogenase-mutated intrahepatic cholangiocarcinomas. Eur J Cancer. 2018;90:83–91.
  • 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 [published correction appears in Lancet Oncol. 2020 Oct;21(10):e462]. Lancet Oncol. 2020;21(6):796–807.
  • Lowery MA, Burris HA 3rd, Janku F, et al. Safety and activity of ivosidenib in patients with IDH1-mutant advanced cholangiocarcinoma: a phase 1 study. Lancet Gastroenterol Hepatol. 2019;4(9):711–720.
  • Kelley RK, Bridgewater J, Gores GJ, et al. Systemic therapies for intrahepatic cholangiocarcinoma. J Hepatol. 2020;72(2):353–363.
  • Galdy S, Lamarca A, McNamara MG, et al. HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target? Cancer Metastasis Rev. 2017;36(1):141–157.
  • Javle M, Churi C, Kang HC, et al. HER2/neu-directed therapy for biliary tract cancer. J Hematol Oncol. 2015;8:58. Published 2015 May 29.
  • Harding J, Cleary J, Shapiro G, et al. O-005—treating HER2-mutant advanced biliary tract cancer with neratinib: benefits of HER2-directed targeted therapy in the phase 2 SUMMIT ‘basket’ trial. Ann Oncol. 2019;30:iv127.
  • Chun YS, Javle M. Systemic and Adjuvant Therapies for Intrahepatic Cholangiocarcinoma. Cancer Control. 2017;24(3):1073274817729241.
  • 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. The Lancet Oncology. 2020;21(9):1234–1243.
  • Personeni N, Lleo A, Pressiani T, et al. Biliary tract cancers: molecular heterogeneity and new treatment options. Cancers (Basel). 2020;12(11):3370.
  • Valle JW, Lamarca A, Goyal L, et al. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 2017;7(9):943–962.
  • Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1(2):e000023.
  • Alqahtani SA, Colombo M. Systemic therapy for advanced cholangiocarcinoma: new options on the horizon. Hepatoma Res. 2020;6. DOI:10.20517/2394-5079.2020.65.
  • U.S. Food and Drug Administration. Center for Drug Evaluation and Research“FDA approves larotrectinib for solid tumors with NTRK gene fusions.” U.S. FDA, 14 December 2018. [cited 2020 Feb 3]. Available from: https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions-0
  • U.S. Food and Drug Administration. Center for Drug Evaluation and Research. “FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC” U.S. FDA, 16 August 2019. [cited 2021 Feb 3]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-entrectinib-ntrk-solid-tumors-and-ros-1-nsclc.
  • Silva VW, Askan G, Daniel TD, et al. Biliary carcinomas: pathology and the role of DNA mismatch repair deficiency. Chin. Clin. Oncol. 2016;5(62):62.
  • Fontugne J, Augustin J, Pujals A, et al. PD- L1 expression in perihilar and intrahepatic cholangiocarcinoma. Oncotarget. 2017;8(15):24644–24651.
  • Gani F, Nagarajan N, Kim Y, et al. Program death 1 immune checkpoint nd tumor microenvironment: implications for patients with intrahepatic cholangiocarcinoma. Ann. Surg. Oncol. 2016;23(8):2610–2617.
  • Ueno M, Chung HC, Nagrial A, et al. Pembrolizumab for advanced biliary adenocarcinoma: results from the multicohort, phase 2 KEYNOTE-158 study. Ann. Oncol. 2018;29(Suppl. 8):viii205–viii270.
  • Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials [published correction appears in Lancet Oncol. 2020 Feb;21(2):e70][published correction appears in Lancet Oncol. 2020 Jul;21(7):e341][published correction appears in Lancet Oncol. 2020 Aug;21(8):e372]. Lancet Oncol. 2020;21(2):271–282.
  • Kim RD, Chung V, Alese OB, et al. A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer. JAMA Oncol. 2020;6(6):888–894.
  • Bang Y-J, Ueno M, Malka D, et al. Pembrolizumab (pembro) for advanced biliary adenocarcinoma: results from the KEYNOTE-028 (KN028) and KEYNOTE-158 (KN158) basket studies.. J Clin Oncol. 2019;5(5):4079.
  • 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.
  • 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. Lancet Oncol. 2020;21(10):1353–1365.
  • Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366:925–931.
  • Roger A, Finet A, Boru B, et al. Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients. Oncoimmunology. 2018;7(7):e1442166.
  • Rodolfo C-S, Ignacio M-O, Juan C-M, et al. Stereotactic ablative radiotherapy combined with immune checkpoint inhibitors reboots the immune response assisted by immunotherapy in metastatic lung cancer: a systematic review. Int J Mol Sci. 2019;20(9):2173.
  • Fiorica F, Belluomini L, Stefanelli A, et al. Immune checkpoint inhibitor nivolumab and radiotherapy in pretreated lung cancer patients: efficacy and safety of combination. Am J Clin Oncol. 2018;41(11):1101–1105.
  • Sharabi A, Kim SS, Kato S, et al. Exceptional response to Nivolumab and stereotactic body radiation therapy (SBRT) in neuroendocrine cervical carcinoma with high tumor mutational burden: management considerations from the center for personalized Cancer therapy at UC san Diego Moores Cancer center. Oncologist. 2017;22:631–637.
  • Qin Q, Nan X, Miller T, et al. Complete local and Abscopal responses from a combination of radiation and Nivolumab in refractory Hodgkin’s lymphoma. Radiat Res. 2018;190:322–329.
  • Liu X, Yao J, Song L, et al. Local and abscopal responses in advanced intrahepatic cholangiocarcinoma with low TMB, MSS, pMMR and negative PD-L1 expression following combined therapy of SBRT with PD-1 blockade. J Immunother Cancer. 2019;7(1):204.
  • Liu ZL, Liu X, Peng H, et al. Anti-PD-1 Immunotherapy and Radiotherapy for Stage IV Intrahepatic Cholangiocarcinoma: a Case Report. Front Med (Lausanne). 2020;7:368. Published 2020 Aug 28.
  • 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.
  • Mahipal A, Tella SH, Kommalapati A, et al. Prevention and treatment of FGFR inhibitor-associated toxicities. Crit Rev Oncol Hematol. 2020;155:103091.
  • Tella SH, Kommalapati A, Borad MJ, et al. Second-line therapies in advanced biliary tract cancers. Lancet Oncol. 2020;21(1):e29–e41.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.