Antibody-Drug Conjugates and Their Potential in the Treatment of Patients with Biliary Tract Cancer.

Simple Summary: Survival for patients with biliary tract cancer (BTC) is poor, especially in the advanced stage, where curative treatments are not available. While chemotherapy and immunotherapy are used in standard practice, antibody–drug conjugates (ADCs) have emerged as a novel therapy option. ADCs potentially enhance cancer cell death and reduce side effects. The anti-HER2 ADC Trastuzumab Deruxtecan (T-Dxd) has shown survival benefit for patients whose tumours are HER2-positive, including a subgroup of BTCs. In April 2024, the regulatory authority FDA approved T-Dxd for adults with unresectable or metastatic HER2-positive solid tumours, including BTCs, lacking other treatment options. Ongoing trials are exploring other potentially actionable BTC molecular alterations. This review will discuss the current evidence and ongoing research in this subject area. Background: Biliary tract cancers (BTCs) are aggressive in nature, often presenting asymptomatically until they are diagnosed at an advanced stage. Surgical resection or liver transplantation are potential curative options. However, a large proportion of patients present with incurable locally advanced or metastatic disease and most of these patients are only eligible for palliative chemotherapy or best supportive care. More recently, targeted therapies have proven beneficial in a molecularly selected subgroup of patients with cholangiocarcinoma who have progressed on previous lines of systemic treatment. However, only a minority of patients with BTCs whose tumours harbour specific molecular alterations can access these therapies. Methods: In relation to ADCs, studies regarding use of antibody–drug conjugates in cancer, particularly in BTCs, were searched in Embase (1974 to 2024) and Ovid MEDLINE(R) (1946 to 2024) to obtain relevant articles. Examples of current clinical trials utilising ADC treatment in BTCs were extracted from the ClinicalTrials.gov trial registry. Conclusions: Overall, this review has highlighted that ADCs have shown encouraging outcomes in cancer therapy, and this should lead to further research including in BTCs, where treatment options are often limited. The promising results observed with ADCs in various cancers underscore their potential as a transformative approach in oncology, warranting continued exploration and development and the need for education on the management of their specific toxicities. By addressing current challenges and optimising ADC design and application, future studies could potentially improve treatment outcomes for patients with BTCs and beyond, potentially in both early and advanced stage settings. [ABSTRACT FROM AUTHOR]