The GAP system was found to predict actionable genetic alterations including FGFR2 and IDH. HERIZON-BTC-01 marks the largest phase IIb clinical trial to date for patients with previously treated HER2-positive disease. In several different types of cancer, tumor budding is linked to poor survival outcomes. While biliary tract cancer is one of the fastest-growing types of early-onset cancers, little is known about its biology. Patients with chemotherapy-responsive disease typically undergo observation after 6 months of gemcitabine-based therapy. Adding nanoliposomal irinotecan to fluorouracil plus leucovorin did not improve PFS or OS in cholangiocarcinoma. Participants received pemigatinib 13.5 mg once per day for 21-day cycles with 2 weeks on and 1 week off. The study's primary end point was overall survival. As gem/cis is linked to low survival times, various trials have attempted to improve first-line therapy outcomes for CCA. Drs. Ebben and Uboha break down the importance of the QUIC study, a phase 2 investigation of first-line treatment of BTC. Richard Finn, MD, of University of California, Los Angeles, highlights 3-year follow-up data from KEYNOTE-966. Treatment-related adverse events were mostly sitravatinib related and included hand-foot syndrome and hypertension. A study investigated atezolizumab with varlilumab, an anti-CD27 human antibody, with or without cobimetinib, a MEK inhibitor. Determining which patients can benefit the most from immunotherapy remains elusive. TOPAZ-1's 3-year follow-up is the longest survival follow-up for a global, randomized phase III trial in this setting. Dr. William Jarnagin discusses his recent study on characterizing the heterogeneity of intrahepatic cholangiocarcinoma. This approval marks the first tumor-agnostic approval of a HER2-directed therapy. Dr. Abou-Alfa describes the promising outcomes of infigratinib and delves into further research on FGFR alterations in CCA. Patients who underwent targeted therapy for IDH1/2 alterations or FGFR2 fusions showed a 100% concordance rate. The developed nomogram was found to provide significant diagnostic accuracy with an area under the curve level of 0.882.