OBJECTIVES: BTC are rare, aggressive malignancies typically diagnosed when disease is metastatic or unresectable, precluding curative treatment. This literature review aimed to identify treatment guidelines and real-world treatment patterns and outcomes for unresectable advanced and metastatic BTC.

METHODS: Databases (MEDLINE, Embase, Evidence-Based Medicine Reviews) were searched between January 1^st 2000–November 25^th 2021, and supplemented by hand-searching grey literature. Eligible records were 1) treatment guidelines, and 2) observational studies reporting real-world treatment outcomes, for unresectable advanced or metastatic BTC. Only multi-country studies and those performed in UK, Germany, France, Australia, Canada, and South Korea were included, to pragmatically restrict the broad search strategy while maintaining representation of a wide range of BTC incidences.

RESULTS: 50 studies were identified. 25 (50%) and 9 (18%) reported first- and second-line treatment outcomes, respectively; 22 (44%) reported outcomes for treatment lines described as ‘palliative’ only. Among first-line studies, outcomes for chemotherapy were most frequently described (23/25 studies), and gem/cis was the most common chemotherapy (10/23 studies). Median overall survival (mOS) with first-line chemotherapy was <12 months in most studies (15/23; range 4.7–27.7 months). Almost all second-line studies (8/9) described outcomes for chemotherapy, most commonly for fluoropyrimidine-based chemotherapy (5/8 studies). mOS with second-line chemotherapy was <12 months in 5/8 studies (range 4.9–21.5 months). Real-world treatment patterns aligned well with guidelines, which recommend gem/cis as first-line standard-of-care and fluoropyrimidine-based chemotherapy at second-line. No real-world outcomes were identified for new targeted second-line treatments included in the latest guidelines.

CONCLUSIONS: Current chemotherapy options for unresectable advanced and metastatic BTC show poor real-world survival. Although gem/cis was established as standard-of-care a decade ago, gem/cis remains the most used first-line chemotherapy, highlighting the lack of innovation in the treatment landscape. There is an urgent unmet need for new treatments with improved outcomes for unresectable advanced and metastatic BTC.