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ABSTRACTIntroductionCholangiocarcinoma (CCA) frequently presents with an advanced disease precluding curative surgery and shows modest response to chemotherapy. Advancements in genomic profiling have unfolded critical pathophysiologic underpinnings of CCA, leading to the development of targeted therapies with encouraging early results. Of the targetable genomic alterations, fibroblast growth factor receptor-2 (FGFR-2) fusions or rearrangements are present in 10–15% of patients with intrahepatic CCA. Clinical trials demonstrating significant antitumor activity of FGFR inhibitors in FGFR-2fusion or rearrangement enriched chemotherapy-refractory patients led to FDA approval of FGFR inhibitors, pemigatinib and infigratinib, in the second-line setting. We identified peer-reviewed articles on FGFR inhibitors utilizing the PubMed database published between 2015 and 2021.Areas coveredThis article provides an overview of clinical and biological characteristics of FGFR-driven CCA, pharmacology and antitumor activity of currently available FGFR inhibitors, and the evolving knowledge of drug resistance mechanisms. Additionally, toxicities associated with FGFR inhibitor use and their management have been described.Expert opinionThe development of FGFR inhibitors is a significant advancement in the therapeutic paradigm of advanced CCA. Ongoing research utilizing FGFR inhibitors in treatment-naïve patients, elucidation of resistance mechanisms to harness future trials, and exploration of combination strategies will transform the treatment landscape of CCA.

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Ding: Merck: Research Funding. Kay:Hospira: Research Funding; Tolero Pharma: Research Funding; Genentech: Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding. Shanafelt:Glaxo-Smith_Kline: Research Funding; Pharmactckucs: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Cephalon: Research Funding; Janssen: Research Funding; Hospira: Research Funding; Polyphenon E Int'l: Research Funding.

Introduction: Ibrutinib has shown remarkable safety and efficacy in CLL. Due to CYP3A4 (3A4) metabolism, the concurrent use of 3A4 inhibitors/inducers with ibrutinib should be avoided. Ibrutinib is also associated with bleeding complications, in part due to effects on collagen-mediated platelet aggregation, thus caution is advised with the simultaneous use of anticoagulant (AC) and antiplatelet agents. It is unknown what proportion of CLL patients starting ibrutinib therapy in routine practice are on these medications. We conducted a retrospective study to evaluate these aspects in a large cohort of CLL pts treated with ibrutinib outside the context of clinical trials.