The Lynx Group
Cholangiocarcinoma News

Natural History of Fibroblast Growth Factor Receptor–Altered Cholangiocarcinoma

Web Exclusives — May 28, 2020

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.

Reference

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

Related Items

Phase 1 Results of Gunagratinib in Patients with Advanced Solid Tumors Harboring FGFR Pathway Alterations
2021 Year in Review: Cholangiocarcinoma
A phase 1/2a, first-in-human clinical study demonstrated that the highly selective, irreversible pan-FGFR inhibitor gunagratinib was safe and well-tolerated in patients with advanced solid tumors, including CCA.
Prognostic Value of FGFR2 Alterations in Patients Receiving Systemic Chemotherapy for Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
A retrospective analysis indicated the prognostic value of FGFR2 fusions/rearrangements in patients with intrahepatic CCA receiving systemic chemotherapy, which warrants additional study.
FGFR2 Fusion and/or Rearrangement Profiling in Chinese Patients with Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
Epidemiologic data assessed the incidence rate of FGFR2 gene fusion or rearrangement in Chinese patients with intrahepatic CCA, including those with heterogeneous FGFR2 partner genes.
A Comprehensive Genomic and Immune Profiling Study of IDH1- and IDH2-Driven Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
A comprehensive genomic and immune characterization of IDH-mutated and wild-type intrahepatic CCA revealed significant differences in genetic alterations.
Characteristics of IDH Mutations in Bile Duct Carcinoma in a Chinese Population
2021 Year in Review: Cholangiocarcinoma
A retrospective analysis in a large Chinese patient cohort with bile duct carcinoma indicated that activating IDH1/2 mutations occurred at a lower rate compared with that previously reported in the global population.
Silmitasertib (CX-4945) plus Gemcitabine and Cisplatin as First-Line Treatment for Patients with Locally Advanced or Metastatic CCA
2021 Year in Review: Cholangiocarcinoma
Preliminary evidence suggests that combination treatment with silmitasertib plus gemcitabine/cisplatin as first-line therapy has promising efficacy and a favorable safety profile in patients with locally advanced or metastatic CCA.
Targeted Therapies in CCA: Assessment of US Oncologist Practice Patterns
2021 Year in Review: Cholangiocarcinoma
Findings from a clinical practice assessment identified gaps in knowledge, competence, and confidence regarding testing and the use of targeted therapies in patients with unresectable CCA, underscoring the important role of education in overcoming these gaps.
First-Line Toripalimab plus Lenvatinib in Combination with GemOx Chemotherapy for Advanced Intrahepatic CCA
2021 Year in Review: Cholangiocarcinoma
Results of a phase 2 study indicate that toripalimab and lenvatinib in combination with GemOx chemotherapy provide antitumor activity and reasonable tolerability in patients with advanced intrahepatic CCA.
Comparative Landscape of Actionable Somatic Alterations in Advanced CCA from Circulating Tumor and Tissue-Based DNA Profiling
2021 Year in Review: Cholangiocarcinoma
Findings from a retrospective analysis support the use of both tissue and liquid biopsy biomarker testing to guide therapy selection in patients with advanced CCA, particularly when tissue may not be readily available.
Tibsovo (Ivosidenib) FDA Approved for Advanced or Metastatic Cholangiocarcinoma and IDH1 Mutation
By Loretta Fala
2021 Year in Review: Cholangiocarcinoma
Cholangiocarcinoma (CCA) is an aggressive cancer of the bile duct that forms inside the liver (ie, intrahepatic) or outside the liver (ie, extrahepatic, including perihilar and distal tumors). Individuals with colitis or certain liver diseases may have an increased risk for CCA. Although the precise incidence of CCA is unknown, an estimated 8000 new cases of CCA are diagnosed annually in the United States. It is likely, however, that this number is higher, because CCA is difficult to diagnose and may be misclassified at times.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: