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

Search for other papers by Al B. Benson III in
Current site
Google Scholar
PubMed
Close
 MD
,
Michael I. D’Angelica Memorial Sloan Kettering Cancer Center

Search for other papers by Michael I. D’Angelica in
Current site
Google Scholar
PubMed
Close
 MD
,
Thomas Abrams Dana-Farber/Brigham and Women’s Cancer Center

Search for other papers by Thomas Abrams in
Current site
Google Scholar
PubMed
Close
 MD
,
Daniel E. Abbott University of Wisconsin Carbone Cancer Center

Search for other papers by Daniel E. Abbott in
Current site
Google Scholar
PubMed
Close
 MD
,
Aijaz Ahmed Stanford Cancer Institute

Search for other papers by Aijaz Ahmed in
Current site
Google Scholar
PubMed
Close
 MD
,
Daniel A. Anaya Moffitt Cancer Center

Search for other papers by Daniel A. Anaya in
Current site
Google Scholar
PubMed
Close
 MD
,
Robert Anders The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Search for other papers by Robert Anders in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Chandrakanth Are Fred & Pamela Buffett Cancer Center

Search for other papers by Chandrakanth Are in
Current site
Google Scholar
PubMed
Close
 MD, MBA
,
Melinda Bachini The Cholangiocarcinoma Foundation

Search for other papers by Melinda Bachini in
Current site
Google Scholar
PubMed
Close
,
David Binder University of Colorado Cancer Center

Search for other papers by David Binder in
Current site
Google Scholar
PubMed
Close
 MD
,
Mitesh Borad Mayo Clinic Comprehensive Cancer Center

Search for other papers by Mitesh Borad in
Current site
Google Scholar
PubMed
Close
 MD
,
Christopher Bowlus UC Davis Comprehensive Cancer Center

Search for other papers by Christopher Bowlus in
Current site
Google Scholar
PubMed
Close
 MD
,
Daniel Brown Vanderbilt-Ingram Cancer Center

Search for other papers by Daniel Brown in
Current site
Google Scholar
PubMed
Close
 MD
,
Adam Burgoyne UC San Diego Moores Cancer Center

Search for other papers by Adam Burgoyne in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Jason Castellanos Fox Chase Cancer Center

Search for other papers by Jason Castellanos in
Current site
Google Scholar
PubMed
Close
 MD, MS
,
Prabhleen Chahal Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute

Search for other papers by Prabhleen Chahal in
Current site
Google Scholar
PubMed
Close
 MD
,
Jordan Cloyd The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

Search for other papers by Jordan Cloyd in
Current site
Google Scholar
PubMed
Close
 MD
,
Anne M. Covey Memorial Sloan Kettering Cancer Center

Search for other papers by Anne M. Covey in
Current site
Google Scholar
PubMed
Close
 MD
,
Evan S. Glazer The University of Tennessee Health Science Center

Search for other papers by Evan S. Glazer in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
William G. Hawkins Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Search for other papers by William G. Hawkins in
Current site
Google Scholar
PubMed
Close
 MD
,
Renuka Iyer Roswell Park Comprehensive Cancer Center

Search for other papers by Renuka Iyer in
Current site
Google Scholar
PubMed
Close
 MD
,
Rojymon Jacob O’Neal Comprehensive Cancer Center at UAB

Search for other papers by Rojymon Jacob in
Current site
Google Scholar
PubMed
Close
 MD
,
Lawrence Jennings Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Search for other papers by Lawrence Jennings in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
R. Kate Kelley UCSF Helen Diller Family Comprehensive Cancer Center

Search for other papers by R. Kate Kelley in
Current site
Google Scholar
PubMed
Close
 MD
,
Robin Kim Huntsman Cancer Institute at the University of Utah

Search for other papers by Robin Kim in
Current site
Google Scholar
PubMed
Close
 MD
,
Matthew Levine Abramson Cancer Center at the University of Pennsylvania

Search for other papers by Matthew Levine in
Current site
Google Scholar
PubMed
Close
 MD, PhD
,
Manisha Palta Duke Cancer Institute

Search for other papers by Manisha Palta in
Current site
Google Scholar
PubMed
Close
 MD
,
James O. Park Fred Hutchinson Cancer Center

Search for other papers by James O. Park in
Current site
Google Scholar
PubMed
Close
 MD
,
Steven Raman UCLA Jonsson Comprehensive Cancer Center

Search for other papers by Steven Raman in
Current site
Google Scholar
PubMed
Close
 MD
,
Sanjay Reddy Fox Chase Cancer Center

Search for other papers by Sanjay Reddy in
Current site
Google Scholar
PubMed
Close
 MD
,
Sean Ronnekleiv-Kelly University of Wisconsin Carbone Cancer Center

Search for other papers by Sean Ronnekleiv-Kelly in
Current site
Google Scholar
PubMed
Close
 MD
,
Vaibhav Sahai University of Michigan Rogel Cancer Center

Search for other papers by Vaibhav Sahai in
Current site
Google Scholar
PubMed
Close
 MBBS, MS
,
Gagandeep Singh City of Hope National Medical Center

Search for other papers by Gagandeep Singh in
Current site
Google Scholar
PubMed
Close
 MD
,
Stacey Stein Yale Cancer Center/Smilow Cancer Hospital

Search for other papers by Stacey Stein in
Current site
Google Scholar
PubMed
Close
 MD
,
Anita Turk Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Search for other papers by Anita Turk in
Current site
Google Scholar
PubMed
Close
 MD
,
Jean-Nicolas Vauthey The University of Texas MD Anderson Cancer Center

Search for other papers by Jean-Nicolas Vauthey in
Current site
Google Scholar
PubMed
Close
 MD
,
Alan P. Venook UCSF Helen Diller Family Comprehensive Cancer Center

Search for other papers by Alan P. Venook in
Current site
Google Scholar
PubMed
Close
 MD
,
Adam Yopp UT Southwestern Simmons Comprehensive Cancer Center

Search for other papers by Adam Yopp in
Current site
Google Scholar
PubMed
Close
 MD
,
Nicole McMillian National Comprehensive Cancer Network

Search for other papers by Nicole McMillian in
Current site
Google Scholar
PubMed
Close
 MS
,
Ryan Schonfeld National Comprehensive Cancer Network

Search for other papers by Ryan Schonfeld in
Current site
Google Scholar
PubMed
Close
 BA
, and
Cindy Hochstetler National Comprehensive Cancer Network

Search for other papers by Cindy Hochstetler in
Current site
Google Scholar
PubMed
Close
 PhD
Restricted access

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.

  • Collapse
  • Expand
  • 1.

    Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin 2023;73:1748.

  • 2.

    Park J, Kim MH, Kim KP, et al. Natural history and prognostic factors of advanced cholangiocarcinoma without surgery, chemotherapy, or radiotherapy: a large-scale observational study. Gut Liver 2009;3:298305.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

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

  • 4.

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    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

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Maynard H, Stadler ZK, Berger MF, et al. Germline alterations in patients with biliary tract cancers: a spectrum of significant and previously underappreciated findings. Cancer 2020;126:19952002.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Samadder NJ, Riegert-Johnson D, Boardman L, et al. Comparison of universal genetic testing vs guideline-directed targeted testing for patients with hereditary cancer syndrome. JAMA Oncol 2021;7:230237.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    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.

  • 9.

    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. Lancet Oncol 2020;21:271282.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Sicklick JK, Kato S, Okamura R, et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat Med 2019;25:744750.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Schenker M, Burotto M, Richardet M, et al. CheckMate 848: a randomized, open-label, phase 2 study of nivolumab in combination with ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden. Cancer Res 2022;82(12 Suppl):Abstract CT022.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Piha-Paul SA, Oh DY, 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. Int J Cancer 2020;147:21902198.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    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;6:888894.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

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

  • 17.

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Hyman DM, Piha-Paul SA, Won H, et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 2018;554:189194.

  • 25.

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Hong DS, Fakih MG, Strickler JH, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med 2020;383:12071217.

  • 30.

    Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med 2021;384:23712381.

  • 31.

    Goyal L, Zheng H, Yurgelun MB, et al. A phase 2 and biomarker study of cabozantinib in patients with advanced cholangiocarcinoma. Cancer 2017;123:19791988.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

  • 34.

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

  • 37.

    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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 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.

    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 22646 9404 802
PDF Downloads 18138 5759 424
EPUB Downloads 0 0 0