The following is a summary of the “Rational development of combination therapies for biliary tract cancers,” published in the January 2023 issue of Hepatology by Harding, et al.

Cancers of the biliary system are a rare kind of gastrointestinal cancer with a high morbidity and mortality rate. Most patients arrive with locally progressed or metastatic illnesses, both terminal. Chemotherapy, precision medicine, immunotherapy, and combination treatments are now used as the standard of care and exploratory therapies for biliary tract cancer, a disease with a pathophysiology that can be exploited for direct therapeutic benefit. 

The immune-based chemotherapy combination of durvalumab, gemcitabine, and cisplatin has recently been found to increase survival in the first-line context, compared to chemotherapy alone. Individuals with specific genetic alterations such as those in IDH1/2 (isocitrate dehydrogenase 1/2), FGFR2 (fibroblast growth factor receptor 2), KRAS, BRAF, ERBB2, NTRK (neurotrophic receptor tyrosine kinase), ROS, RET, and/or deficiencies in mismatch repair enzymes may benefit from precision medicine as a second-line treatment option. Fluoropyridine doublets result in moderate improvements in outcomes in people who do not have targetable genetic abnormalities. 

Both in the context of direct patient care and research into the genetic underpinnings of resistance, next-generation sequencing has become indispensable. This review aims to update readers on the latest developments in standards of care and ongoing investigational agents, discuss the limitations of currently available treatments, and lay the groundwork for future successful combination drug development because many clinical trials are currently underway.

Source: sciencedirect.com/science/article/pii/S0168827822030781