Advanced Bile Duct Cancers: A Focused Review on Current and Emerging Systemic Treatments

Abstract

Cancers arising in the biliary tract are rare, with varied incidence depending on geographical location. As clinical presentation is typically vague with non-specific symptoms, a large proportion of patients present with unresectable or metastatic disease at diagnosis. When unresectable, the mainstay of treatment is cytotoxic chemotherapy; however, despite this, 5-year overall survival remains incredibly poor. Diagnostic molecular pathology, using next-generation sequencing, has identified a high prevalence of targetable alterations in bile duct cancers, which is transforming care. Substantial genomic heterogeneity has been identified depending on both the anatomical location and etiology of disease, with certain alterations enriched for subtypes. In addition, immune checkpoint inhibitors with anti-PD-1/PD-L1 antibodies in combination with chemotherapy are now poised to become the standard first-line treatment option in this disease. Here, we describe the established role of cytotoxic chemotherapy, targeted precision treatments and immunotherapy in what is a rapidly evolving treatment paradigm for advanced biliary tract cancer.

Keywords: cholangiocarcinoma; gallbladder cancer; immunotherapy; precision medicine; systemic therapy.

Figure 2

Most common genomic alterations identified based on anatomic location of biliary tract cancer. Frequency of alterations listed is based on Nakamura et al. Nat. Genet. 2015 [10], Lowery et al. Clin. Cancer Res. 2018 [12], Javle et al. Cancer 2016 [13] and Wardell et al. J. Hepatol. 2018 [11].

Figure 1

Timeline of systemic treatments developed for the treatment of advanced biliary tract cancer.