The Lynx Group

Natural History of Fibroblast Growth Factor Receptor–Altered Cholangiocarcinoma

Conference Correspondent

Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are emerging as promising therapeutic targets in cholangiocarcinoma (CCA). A retrospective chart review was performed in patients with CCA who were found to have an FGFR alteration on tumor molecular profiling as part of routine care.1 Data on demographics, risk factors, pathology, molecular characteristics, systemic therapies, radiographic response, time on treatment, and overall survival (OS) were collected in a multicenter collaborative effort across 7 academic centers.

A total of 135 patients with FGFR-altered CCA were included in the review. The median age at diagnosis was 57 years (range, 25-92 years), 80 (59.3%) patients were female, 129 (95.6%) had intrahepatic CCA, and 6 (5.6%) had chronic hepatitis B virus. At presentation, 28.2% of patients had resectable disease, including 65.0% with stage I-II, 22.5% with stage III, and 5.0% with stage IV. At the time of initial diagnosis, CA19-9 level was <35 U/mL in 42.6% of patients. Bone metastases were observed in 41 (30.6%) patients with advanced disease. FGFR2 fusions were the most common FGFR alteration (68.2%), followed by FGFR2 mutations (21.5%), FGFR3 mutations (3.7%), FGFR2 rearrangements (1.5%), FGFR1 amplification (1.5%), and FGFR2 amplification (1.5%). The most common FGFR2 fusion partners were BICC1 (28.3%), SORBS1 (4.4%), POC1B (3.3%), and TACC2 (3.3%).

The median lines of palliative systemic therapies received was 3 (range, 0-8), and 40 of 135 (29.6%) patients received liver-directed therapy. For the 55 (59.8%) patients with FGFR2 fusions who received gemcitabine/cisplatin as first-line palliative systemic therapy, the median time on treatment was 6.2 months The median OS from time of initial diagnosis was 36.1 months in the FGFR2 fusion–positive cohort. Among the 92 patients with FGFR2 fusions, 70 (76.1%) patients received an FGFR inhibitor on a clinical trial; 12 (17.1%) were subsequently treated with a second FGFR inhibitor, and 58.3% stayed on the second FGFR inhibitor for ≥4 months. Patients with a BICC1 fusion partner (n = 16) had an overall response rate of 42.9% on FGFR-selective inhibitors compared with 30.8% in non-BICC1 fusion partners (n = 54).

The authors observed that patients with CCA harboring FGFR alterations were found to have a high rate of normal CA19-9, a high rate of bone metastases, and short median time on treatment with first-line palliative gemcitabine/cisplatin. They also noted that additional comparative studies would be necessary to evaluate these findings.


  1. Goyal L, et al. ASCO 2020. Abstract e16686.

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