Systemic treatment options for advanced biliary tract carcinoma
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REVIEW
Systemic treatment options for advanced biliary tract carcinoma Changqing Xie1
•
Nicole A. McGrath1 • Cecilia Monge Bonilla1 • Jianyang Fu1
Received: 19 May 2020 / Accepted: 25 July 2020 Ó The Author(s) 2020
Abstract Advanced biliary tract cancers (BTC) include a diverse collection of rare and heterogenous tumors with poor prognosis. The combination of gemcitabine and cisplatin is the established first-line therapy for advanced BTC. There are no accepted standard treatments in the second line setting, though there are several ongoing clinical trials that implement chemotherapy as a therapeutic strategy. The understanding of the molecular landscape of BTC has offered hope of targeted therapies to the identified actionable genomic aberrations, such as FGFR2 gene fusions, mutations of IDH1/2, HER2, BRAC1/2 and BRAF. Pembigatinib has become the first approved targeted therapy for BTC with FGFR2 fusion or other rearrangements. Recent immunotherapy has opened new therapy avenues in BTC with pembrolizumab approved for either microsatellite instability high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors, including BTC. The combination of immunotherapy with other modalities is currently being evaluated in different clinical trials, since single agent immunotherapy appears to provide modest benefits in advanced BTC. In this review, we summarize the current status of treatment options, including systemic chemotherapy, targeted therapy, immunotherapy, and various combinations in advanced BTC. Keywords Biliary tract cancer Chemotherapy Targeted therapy Immunotherapy
& Changqing Xie [email protected] 1
Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Introduction Biliary tract carcinoma (BTC) typically refers to malignancies originating in the intra- and extrahepatic biliary ductal system, known as cholangiocarcinoma (CCA), and the gallbladder; however, periampullary tumors are also included as BTCs. The primary risk factors for intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA) include chronic inflammatory diseases of the biliary tract such as primary sclerosing cholangitis and hepatolithiasis, congenital hepatobiliary anomalies, liver fluke infection, non-alcoholic fatty liver disease [1–4]. Moreover, cholelithiasis with the presence of chronic inflammation is the most prevalent risk factor for gallbladder cancer (GBC) [5]. The anatomic subtypes of BTC display distinguished molecular aberrations [6], that suggests complexities of pathogenesis of BTC. Commonly occurring genetic aberrations in iCCA include TP53 (35%), KRAS (24%), ARID1A (20%), IDH1 (18%), MCL1 (16%), and PBRM1 (11%). In contrast, the most frequent aberrations in eCCA are TP53 (45%), KRAS (40%), ERBB2 (25%), SMAD4 (25%), FBXW7 (15%) and CDKN2A (15%) [7]. The clinical presentation of BTC differs with their sites, that patients with eCCA usually present with symptoms and painless jau
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