Abstract
Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.
Highlights
Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors that originate from the epithelium of intrahepatic (IHCC), extrahepatic (EHCC), distal biliary tree, or from the gallbladder (GBC) [1]
isocitrate dehydrogenase 1 (IDH1) mutations and fibroblast growth factor receptor 2 (FGFR2) fusions were almost reported in intrahepatic cholangiocarcinoma, while extrahepatic had a higher frequency of KRAS, CDKN2A, and BRCA1 mutations; extrahepatic and gallbladder cancer had higher rates of homologous recombination repair deficiency and HER2 overexpression/amplification
The IMMUNOBIL PRODIGE 57 study assessed the combination of durvalumab/tremelimumab plus paclitaxel in patients with BTC that progressed to cisplatin/gemcitabine treatment [74]
Summary
Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors that originate from the epithelium of intrahepatic (IHCC), extrahepatic (EHCC), distal biliary tree, or from the gallbladder (GBC) [1]. Cholangiocarcinoma has been considered an orphan disease with very limited therapeutic options In this scenario, a milestone was represented in 2010 by the ABC-02 trial that proved the efficacy of cisplatin plus gemcitabine as the standard of care (SOC) for patients with metastatic BTC [7]. The ABC-06 trial established the FOLFOX regimen, based on a small but significant improvement in survival compared with placebo, as the new SOC following failure of cisplatin plus gemcitabine [9]. After these two lines of treatments, no other therapeutic options are currently approved in the unselected population. The aim of this review is to light on the possible role and place of immunotherapy in the continuum of treatment of BTC with a critical analysis of completed trials, focusing on future perspectives and possible biomarkers of response
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
