Abstract
Cholangiocarcinomas (CCA) are a group of heterogeneous tumors arising from the biliary system. Significant sequencing efforts have provided further insights on the molecular mechanisms of this disease including fibroblast growth factor receptor (FGFR) alterations, which occurs in approximately 15-20% of intrahepatic cholangiocarcinomas. There is lack of data on outcomes of patients following cessation of FGFR inhibitor (FGFRi) therapy. Herein, we described the patient characteristics and treatment outcomes among patients with cholangiocarcinoma harboring FGFR alterations treated with chemotherapy, another targeted therapy or a second FGFRi following treatment with a first FGFRi from a multi-center single institution experience. We conducted a retrospective study of patients with pathologic confirmed diagnosis of cholangiocarcinoma treated at the Mayo Clinic Enterprise. The study was reviewed and approved by the institutional review board. The identified patients had FGFR alterations obtained from clinical genomic reports. The primary outcome was overall survival (OS) and progression free survival (PFS). Our group identified 88 advanced or metastatic cholangiocarcinoma patients, 28 males (31.8%) and 60 females (68.2%), harboring FGFR alterations who received FGFRi. Median progression free survival (PFS) on first FGFRi was 6.6 months for all patients (95% CI: 5.5 – 8.3). Following cessation of first FGFRi therapy 55% of patients received systemic therapy as next line: 67% chemotherapy or other targeted treatment and 33% received another FGFRi therapy. Median PFS for patients who received chemotherapy or other targeted agent was 2.1 months (95% CI: 1.6 – 5.7) and for patients who received a second FGFRi following first FGFRi therapy was 3.7 months (95% CI: 1.5 – not evaluable). 28% (N=25) of the patients received another FGFRi as any line after first FGFRi therapy and median PFS was 4.0 months. This is a large multi-center single institution cohort study assessing the outcomes among patients with cholangiocarcinoma treated with a second FGFRi or chemotherapy after initial treatment with FGFR inhibitors. This data reflects the real-world experience at a tertiary cancer center. Following FGFRi treatment, almost half of the patients are able to receive next line of therapy. As more novel agents are being introduced and the optimal sequencing of FGFRi is under investigation, detailed understanding of outcomes following treatment with an FGFRi is essential.
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