Conventional chemotherapy for advanced-stage biliary tract cancers (BTCs) is associated with median overall survival (OS) durations of <12 months. In 2022, however, the FDA approved durvalumab in combination with first-line chemotherapy based on a significant OS improvement in the phase III TOPAZ-1 trial. Now, data from the phase III KEYNOTE-966 trial of pembrolizumab cement chemoimmunotherapy as the new frontline standard-of-care treatment for these cancers.