Advances in the systemic treatment of therapeutic approaches in biliary tract cancer

• Published in: ESMO open Vol. 7; no. 3; p. 100503
• Main Authors: Mirallas, O., López-Valbuena, D., García-Illescas, D., Fabregat-Franco, C., Verdaguer, H., Tabernero, J., Macarulla, T.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2022; Elsevier
• Subjects: biliary tract cancer; cholangiocarcinoma; molecular testing; next-generation sequencing; Review; targeted therapies; biliary tract cancer; targeted therapies; molecular testing; next-generation sequencing; cholangiocarcinoma
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2022.100503

Biliary tract cancers (BTCs) are a rare and heterogenous group with an increasing incidence and high mortality rate. The estimated new cases and deaths of BTC worldwide are increasing, but the incidence and mortality rates in South East Asia are the highest worldwide, representing a real public health problem in these regions. BTC has a poor prognosis with a median overall survival <12 months. Thus, an urgent unmet clinical need for BTC patients exists and must be addressed. The backbone treatment of these malignancies is chemotherapy in first- and second-line setting, but in the last decade a rich molecular landscape has been discovered, expanding conceivable treatment options. Some druggable molecular aberrations can be treated with new targeted therapies and have already demonstrated efficacy in patients with BTC, improving clinical outcomes, such as the FGFR2 or IDH1 inhibitors. Many other molecular alterations are being discovered and the treatment of BTC will change in the near future from our current clinical practice. In this review we discuss the epidemiology, molecular characteristics, present treatment approaches, review the recent therapeutic advances, and explore future directions for patients with BTC. Due to the rich molecular landscape of BTC, molecular profiling should be carried out early. Ongoing research will bring new targeted treatments and immunotherapy in the near future. •BTCs are a heterogenous group of tumors with a poor prognosis.•Surgery is the only curative treatment of BTC.•Cisplatin plus gemcitabine still remains the standard of care in the first-line setting. Immunotherapy may replace this in the near future.•FOLFIRI, XELIRI, and nal-IRI are promising new options for second-line setting.•BTCs have multiple molecular alterations potentially targetable. It is highly recommended to obtain a molecular analysis.