NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023

Featured Updates to the NCCN Guidelines

Authors:
Al B. Benson III Robert H. Lurie Comprehensive Cancer Center of Northwestern University

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Michael I. D’Angelica Memorial Sloan Kettering Cancer Center

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Thomas Abrams Dana-Farber/Brigham and Women’s Cancer Center

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Daniel E. Abbott University of Wisconsin Carbone Cancer Center

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Aijaz Ahmed Stanford Cancer Institute

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Daniel A. Anaya Moffitt Cancer Center

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Robert Anders The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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Chandrakanth Are Fred & Pamela Buffett Cancer Center

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Melinda Bachini The Cholangiocarcinoma Foundation

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David Binder University of Colorado Cancer Center

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Mitesh Borad Mayo Clinic Comprehensive Cancer Center

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Christopher Bowlus UC Davis Comprehensive Cancer Center

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Daniel Brown Vanderbilt-Ingram Cancer Center

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Adam Burgoyne UC San Diego Moores Cancer Center

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Jason Castellanos Fox Chase Cancer Center

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Prabhleen Chahal Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute

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Jordan Cloyd The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

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Anne M. Covey Memorial Sloan Kettering Cancer Center

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Evan S. Glazer The University of Tennessee Health Science Center

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William G. Hawkins Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

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Renuka Iyer Roswell Park Comprehensive Cancer Center

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Rojymon Jacob O’Neal Comprehensive Cancer Center at UAB

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Lawrence Jennings Robert H. Lurie Comprehensive Cancer Center of Northwestern University

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R. Kate Kelley UCSF Helen Diller Family Comprehensive Cancer Center

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Robin Kim Huntsman Cancer Institute at the University of Utah

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Matthew Levine Abramson Cancer Center at the University of Pennsylvania

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Manisha Palta Duke Cancer Institute

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James O. Park Fred Hutchinson Cancer Center

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Steven Raman UCLA Jonsson Comprehensive Cancer Center

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Sanjay Reddy Fox Chase Cancer Center

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Sean Ronnekleiv-Kelly University of Wisconsin Carbone Cancer Center

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Vaibhav Sahai University of Michigan Rogel Cancer Center

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Gagandeep Singh City of Hope National Medical Center

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Stacey Stein Yale Cancer Center/Smilow Cancer Hospital

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Anita Turk Indiana University Melvin and Bren Simon Comprehensive Cancer Center

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Jean-Nicolas Vauthey The University of Texas MD Anderson Cancer Center

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Alan P. Venook UCSF Helen Diller Family Comprehensive Cancer Center

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Adam Yopp UT Southwestern Simmons Comprehensive Cancer Center

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Nicole McMillian National Comprehensive Cancer Network

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Ryan Schonfeld National Comprehensive Cancer Network

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Cindy Hochstetler National Comprehensive Cancer Network

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In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

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  • 1.

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  • 3.

    Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid 2022;1:EVIDoa2200015.

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    Yoo C, Kim KP, Jeong JH, et al. Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study. Lancet Oncol 2021;22:15601572.

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    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. Published online March 23, 2023. doi:10.1001/jamaoncol.2023.0016

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    Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 2018;378:731739.

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  • 14.

    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;21:12341243.

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    Salama AKS, Li S, Macrae ER, et al. Dabrafenib and trametinib in patients with tumors with BRAFV600E mutations: results of the NCI-MATCH trial Subprotocol H. J Clin Oncol 2020;38:38953904.

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  • 16.

    Goyal L, Meric-Bernstam F, Hollebecque A, et al. Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma. N Engl J Med 2023;388:228239.

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    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;11:326339.

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  • 18.

    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;21:671684.

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  • 19.

    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;21:796807.

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  • 20.

    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;7:16691677.

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  • 21.

    Ramanathan RK, Belani CP, Singh DA, et al. A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer. Cancer Chemother Pharmacol 2009;64:777783.

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  • 22.

    Peck J, Wei L, Zalupski M, et al. HER2/neu may not be an interesting target in biliary cancers: results of an early phase II study with lapatinib. Oncology 2012;82:175179.

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  • 23.

    Hainsworth JD, Meric-Bernstam F, Swanton C, et al. Targeted therapy for advanced solid tumors on the basis of molecular profiles: results from MyPathway, an open-label, phase IIa multiple basket study. J Clin Oncol 2018;36:536542.

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  • 24.

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    Meric-Bernstam F, Beeram M, Hamilton E, et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. Lancet Oncol 2022;23:15581570.

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  • 26.

    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;22:12901300.

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  • 27.

    Ohba A, Morizane C, Kawamoto Y, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing unresectable or recurrent biliary tract cancer (BTC): an investigator-initiated multicenter phase 2 study (HERB trial). J Clin Oncol 2022;40(Suppl):Abstract 4006.

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  • 28.

    Ou SI, Jänne PA, Leal TA, et al. First-in-human phase I/IB dose-finding study of adagrasib (MRTX849) in patients with advanced KRASG12C solid tumors (KRYSTAL-1). J Clin Oncol 2022;40:25302538.

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  • 29.

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    Pant S, Saleh M, Bendell J, et al. A phase I dose escalation study of oral c-MET inhibitor tivantinib (ARQ 197) in combination with gemcitabine in patients with solid tumors. Ann Oncol 2014;25:14161421.

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  • 33.

    Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 2018;379:5463.

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    Zhou Y, Lizaso A, Mao X, et al. Novel AMBRA1-ALK fusion identified by next-generation sequencing in advanced gallbladder cancer responds to crizotinib: a case report. Ann Transl Med 2020;8:1099.

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  • 35.

    Subbiah V, Cassier PA, Siena S, et al. Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial. Nat Med 2022;28:16401645.

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  • 36.

    Gu TL, Deng X, Huang F, et al. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma. PLoS One 2011;6:e15640.

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    Argani P, Palsgrove DN, Anders RA, et al. A novel NIPBL-NACC1 gene fusion is characteristic of the cholangioblastic variant of intrahepatic cholangiocarcinoma. Am J Surg Pathol 2021;45:15501560.

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  • 38.

    Augustin J, Gabignon C, Scriva A, et al. Testing for ROS1, ALK, MET, and HER2 rearrangements and amplifications in a large series of biliary tract adenocarcinomas. Virchows Arch 2020;477:3345.

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  • 39.

    Subbiah V, Wolf J, Konda B, et al. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Lancet Oncol 2022;23:12611273.

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