The Lynx Group
Cholangiocarcinoma News

Comparative Landscape of Actionable Somatic Alterations in Advanced CCA from Circulating Tumor and Tissue-Based DNA Profiling

2021 Year in Review: Cholangiocarcinoma — December 17, 2021

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.

A retrospective analysis characterized actionable genomic alterations in patients with advanced cholangiocarcinoma (CCA). Results of this analysis were presented at the 2021 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

In this analysis, next-generation sequencing (NGS) data from both circulating tumor and tissue were obtained from patients with advanced CCA. Tempus xT tissue biopsy assay and/or Tempus xF liquid biopsy assay were used to detect germline and/or somatic mutations, including single-nucleotide variants, specific insertion/deletions, amplifications, and gene fusions.

Of the 174 genomic results obtained, 113 were tissue-based NGS results and 61 were liquid-based NGS results. A total of 296 unique alterations were identified. Actionable genetic alterations were identified in 28.8% of the cases, including FGFR2 fusions (6.8%), IDH1/2 (8.4%), BRAF-V600E (2.5%), HER2 (3.0%), MET (0.7%), BRCA1/2/ATM (2%), PIK3CA (4.7%), and ERRFI1 (0.7%). Of these, actionable mutations were found in 33.1% in the ctDNA liquid biopsy cohort and 23.2% in the tissue biopsy cohort. FGFR2 fusion results did not correlate between ctDNA and tissue NGS samples, with FGFR2 fusions being detected in 11.3% of liquid biopsy samples and 3.4% of tissue-based samples.

These data 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.

Source: Kasi PM, Le AD, Barrett A. Comparative landscape of actionable somatic alterations in advanced cholangiocarcinoma from circulating tumor and tissue-based DNA profiling. J Clin Oncol. 2021;39(suppl_3):342-342.

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.
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.
2021 Cholangiocarcinoma Year in Review
By Rachna T. Shroff, MD, MS
2021 Year in Review: Cholangiocarcinoma
This edition of Year in Review is focused on cholangiocarcinoma (CCA), which is a diverse group of malignancies characterized by genomic heterogeneity that potentially drives its pathogenesis. Below is a quick review of some of the topics discussed in this issue, with a focus on recent advances, potentially practice-changing developments, and ongoing challenges in CCA.

Subscribe to CCA News

Stay up to date with personalized medicine by subscribing to receive the free CCA News print publication or weekly e‑Newsletter.

I'd like to receive: