OBJECTIVES: Biliary tract cancer (BTC) is a rare group of malignancies, including gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma, representing less than 1% of adult cancers. BTC often harbors multiple clinically actionable molecular alterations, with expression varying by subtype. Currently, FDA/EMA-approved precision medicines in BTC are only available for FGFR2 and IDH1. As such, a targeted literature review was conducted to define current standard practice in second-line (2L) BTC and the level of utilization of precision medicines in the context of their efficacy.

METHODS: MEDLINE, TRIP, WHO, GIN, and NCCN databases were searched in August 2023 for literature published since 2018. Documents underwent screening/extraction following Cochrane guidance; pre-specified prioritization factors guided selection. Supplementary hand-searches supported and contextualized findings.

RESULTS: 322 clinical guidelines and 423 articles were identified, with 4 guidelines and 26 articles selected for extraction and reporting. For 2L therapy, NCCN and ESMO guidelines recommend FOLFOX as the preferred and standard regimen, respectively, while considering targeted and immuno-therapies linked to actionable alterations and checkpoint blockade therapy. Consistently, FOLFOX/FOLFIRI were the most frequently mentioned 2L treatment options (12 articles; 46%); whereas 6 articles (23%) stated no SOC. NCCN and ESMO guidelines recommend advanced BTC patients receive comprehensive molecular profiling for genetic alterations. Among articles reviewed, HER2, FGFR2, KRAS/MAPK, IDH1/IDH2, BRAF, BRCA, and microsatellite instability were the most discussed actionable alterations, for which immunohistochemistry tests and next-generation sequencing have an important role. Testing for other targets is important, particularly HER2, where several therapies are under clinical investigation.

CONCLUSIONS: In 2L BTC, FOLFOX/FOLFIRI were the most frequently mentioned treatment options, while HER2, FGFR2, KRAS/MAPK, IDH1/IDH2, BRAF, BRCA, and microsatellite instability were the most discussed actionable alterations. Ongoing clinical investigations may cause a shift in the treatment paradigm from chemotherapy to targeted therapies in the context of the efficacy, tolerability, and potential economic value of the latter.