Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are emerging as promising therapeutic targets in patients with cholangiocarcinoma (CCA). A retrospective chart review, led by Lipika Goyal, MD, MPhil, Medical Oncologist, Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital, Boston, was performed in patients with CCA who had an FGFR alteration found by tumor molecular profiling as part of routine care.1 Dr Goyal presented this study at the 2020 ASCO annual meeting.
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 CCA and FGFR alterations were included in the review. The patients’ 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% with stage I to II, 22.5% with stage III, and 5% with stage IV. At the time of the initial diagnosis, the 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 (68.2%) FGFR alteration, 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). Of the 135 total patients, 40 (29.6%) received liver-directed therapy. For the 55 (59.8%) patients with FGFR2 fusions who received gemcitabine plus cisplatin as first-line palliative systemic therapy, the median time of treatment was 6.2 months.
The median OS from the 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 in a clinical trial; 12 (17.1%) subsequently received treatment with a second FGFR inhibitor, and 58.3% continued to receive the second FGFR inhibitor for ≥4 months. Patients with a BICC1 fusion partner (N = 16) had an overall response rate of 42.9% with FGFR-selective inhibitors compared with 30.8% in non–BICC1 fusion partners (N = 54).
The investigators observed that patients with CCA harboring FGFR alterations had a high rate of normal CA19-9 level, a high rate of bone metastases, and a short median time of receiving treatment with first-line palliative gemcitabine plus cisplatin. They also noted that additional comparative studies are necessary to evaluate these findings.
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