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Review
. 2020 Jul;73(1):170-185.
doi: 10.1016/j.jhep.2020.03.007. Epub 2020 Mar 12.

Molecular targeted therapies: Ready for "prime time" in biliary tract cancer

Angela Lamarca  1 , Jorge Barriuso  2 , Mairéad G McNamara  2 , Juan W Valle  3
Affiliations
Review

Molecular targeted therapies: Ready for "prime time" in biliary tract cancer

Angela Lamarca et al. J Hepatol. 2020 Jul.

Abstract

The prognosis for patients with biliary tract cancers (cholangiocarcinoma and gallbladder cancer) is poor, while the incidence of these cancers is increasing. Most patients are diagnosed with advanced disease when treatment options are limited to palliative approaches, mainly focused on chemotherapy. In recent years, novel treatment targets of relevance to biliary tract cancers, mainly present in patients with intrahepatic cholangiocarcinoma, have been identified and are rapidly changing the field. These include fibroblast growth factor receptor (FGFR) fusions and isocitrate dehydrogenase (IDH)-1 and -2 mutations which are each present in around 10-20% of patients with intrahepatic cholangiocarcinoma. In addition, inhibition of other pathways/molecules is currently being explored, including human epidermal growth factor receptor (HER) family members, the Wnt pathway, neurotropic tyrosine kinase receptor (NTRK) fusions and BRAF mutations. The IDH1 inhibitor ivosidenib has already been tested in a phase III clinical trial in pretreated cholangiocarcinoma and showed benefit in terms of progression-free survival. Multiple FGFR inhibitors have consistently shown high response rates in phase II/III trials, especially for patients harbouring FGFR2 fusions. Herein, we provide an overview of the status of targeted therapies in biliary tract cancers, discussing the current clinical development of IDH and FGFR inhibitors in detail, as well as reviewing current caveats and future steps.

Keywords: Biliary tract cancer; Cholangiocarcinoma; FGFR; Fusion; Gallbladder cancer; IDH; Mutation; Targeted therapies.

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Conflict of interest statement

Conflict of interest Angela Lamarca: Travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan and Delcath. Speaker honoraria from Merck, Pfizer, Ipsen and Incyte. Advisory honoraria from EISAI, Nutricia Ipsen, QED and Roche. Member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. Jorge Barriuso: Received travel research and educational support from Ipsen, Pfizer, AAA, Novartis and Nanostring; speaker honoraria from Novartis, Pfizer and Ipsen; advisory honoraria from Nutricia. Mairéad G McNamara: Received research grant support from Servier, Ipsen and NuCana. She has received travel and accommodation support from Bayer and Ipsen and speaker honoraria from Pfizer, Ipsen, NuCana and Mylan. She has served on advisory boards for Celgene, Ipsen, Sirtex and Baxalta; all outside the scope of this work. Juan W Valle: Consulting or Advisory role for Agios, AstraZeneca, Delcath Systems, Keocyt, Genoscience Pharma, Incyte, Ipsen, Merck, Mundipharma EDO, Novartis, PCI Biotech, Pfizer, Pieris Pharmaceuticals, QED and Wren Laboratories; Speakers' Bureau for Imaging Equipment Limited Ipsen Novartis Nucana; and Travel Grants from Celgene and Nucana. Please refer to the accompanying ICMJE disclosure forms for further details.

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