The Lynx Group
Cholangiocarcinoma News

Comparing Primary Tumor, Metastatic Tumor Tissue, and Liquid Biopsy in Intrahepatic Cholangiocarcinoma: Comprehensive Genomic Profiling Study

August 2020, Vol 1, No 1

Genomic alterations that are characteristic of intrahepatic cholangiocarcinoma (CCA) are well known. A study led by Jeffrey S. Ross, MD, Medical Director, Foundation Medicine, Cambridge, MA, examined whether genomic alterations from a primary tumor would differ from metastatic tumor tissue and liquid biopsy in patients with intrahepatic CCA.1 The study results were presented at the 2020 ASCO annual meeting.

Comprehensive genomic profiling was performed on 1268 tissue samples from patients with advanced-stage intrahepatic CCA using primary tumor in 1048 cases, metastatic tumor from 220 cases, and 364 liquid biopsy cases (solid tissue, 318-327 genes; liquid biopsy, 72 genes).1

Tumor mutational burden was determined on the sequenced DNA. PD-L1 expression in tumor cells was measured by immunohistochemistry. The frequencies of untargetable genomic alterations were similar overall. IDH1 and FGFR2 genomic alterations that are known to be enriched in intrahepatic CCA were less frequent in metastatic tumors than in primary tumors.

IDH1 and FGFR2 genomic alterations were identified with liquid biopsy. Genomic alterations uncovered in primary tumors versus metastatic tumors in advanced intrahepatic CCA were significantly different, principally with the metastatic tumor cohort having more KRAS and fewer IDH1 and FGFR2 genomic alterations.

These results suggest that the metastatic tumor group may contain patients without intrahepatic CCA whose metastatic lesions were derived from other primary sites and who were incorrectly diagnosed with intrahepatic CCA.

Liquid biopsy detected more IDH1 genomic alterations than metastatic tumor biopsy, and also detected other potentially targetable alterations.

Reference

  1. Ross JS, Sokol E, Pavlick D, et al. Primary tumor (p-bx) versus metastatic tumor (m-bx) tissue versus liquid biopsy (lb) in intrahepatic cholangiocarcinoma (IHCC): a comparative comprehensive genomic profiling (CGP) study. J Clin Oncol. 2020;38(15_suppl):Abstract 4579.

Related Items

Hot Topics on Cholangiocarcinoma and Biliary Tract Cancer Presented at ASCO 2020
By Milind Javle, MD
August 2020, Vol 1, No 1
Several hot topics were presented at the recent ASCO 2020 annual meeting about cholangiocarcinoma (CCA), which I would briefly discuss here. First, it was very exciting to see 3 important studies regarding immunotherapy for CCA, which may represent a step forward in the development of CCA therapies.
Assessing the Safety, Efficacy, and Biomarkers of Durvalumab in Chemotherapy-Naïve Patients with Advanced Biliary Tract Cancer
August 2020, Vol 1, No 1
Immunotherapies have shown early promising efficacy in some patients with biliary tract cancer. Investigators evaluated the benefit of durvalumab (Imfinzi), a PD-L1 inhibitor, with or without tremelimumab, a CTLA-4 inhibitor, plus chemotherapy with gemcitabine and cisplatin as a first-line treatment for Korean patients with biliary tract cancer. The researchers also performed an extensive biomarker analysis.
Combination Immunotherapy with Ipilimumab and Nivolumab Shows Activity in Patients with Advanced Biliary Tract Cancer
August 2020, Vol 1, No 1
The combination of a CTLA-4 inhibitor and a PD-1 inhibitor with ipilimumab (Yervoy) and nivolumab (Opdivo) has demonstrated superior efficacy compared with single-agent anti–PD-1 therapy in a previous study of patients with advanced melanoma and renal-cell carcinoma.
Nivolumab with Chemotherapy or with Ipilimumab as First-Line Therapy for Patients with Advanced Unresectable Biliary Tract Cancer
August 2020, Vol 1, No 1
Arandomized, phase 2 multi-institutional study compared the role of combination immunotherapy with nivolumab (Opdivo) plus ipilimumab (Yervoy) versus nivolumab plus chemotherapy with gemcitabine and cisplatin in the first-line treatment of patients with advanced biliary tract cancer.
Retrospective Analysis of Post–Second-Line Chemotherapy Outcomes in Patients with Advanced or Metastatic CCA and FGFR2 Fusions
August 2020, Vol 1, No 1
Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with an estimated incidence of 8000 to 10,000 patients annually in the United States. Chemotherapy is the most common second-line treatment with response rates of <10% and median progression-free survival (PFS) of approximately 3 to 4 months, including FOLFOX in the ABC-06 trial. Fibroblast growth factor receptor (FGFR) 2 fusions occur in 13% to 17% of patients with CCA, and multiple targeted agents are in development for patients with FGFR2 fusions. To date, the outcome of patients with CCA and FGFR2 fusions who receive standard second-line chemotherapy is unknown.
Natural History of Cholangiocarcinoma with FGFR Alterations
August 2020, Vol 1, No 1
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.
FOENIX-CCA2: Phase 2 Open-Label Study of Futibatinib in Patients with Intrahepatic Cholangiocarcinoma Harboring FGFR2 Gene Fusions
August 2020, Vol 1, No 1
Futibatinib is a highly selective irreversible fibroblast growth factor receptor (FGFR)1-4 inhibitor, administered as a continuous once-daily oral regimen. The FOENIX-CCA2 phase 2 clinical trial was initiated after the results from a phase 1 dose-escalation/expansion study showed the tolerability and preliminary efficacy of futibatinib in patients with intrahepatic cholangiocarcinoma (CCA) and FGFR2 fusions.
TreeTopp: Phase 2 Study of Varlitinib plus Capecitabine versus Placebo as Second-Line Therapy for Patients with Advanced or Metastatic Biliary Tract Cancer
August 2020, Vol 1, No 1
Varlitinib is a reversible small-molecule, pan human epidermal growth factor receptor (HER) inhibitor with low nanomolar potency against HER1 (EGFR), HER2, and HER4.
Phase 2 Study of Modified FOLFOX versus Modified FOLFIRI in Patients with Locally Advanced or Metastatic Biliary Tract Cancer Refractory to First-Line Chemotherapy
August 2020, Vol 1, No 1
In patients with locally advanced or metastatic biliary tract cancer, treatment with second-line chemotherapy is challenging after disease progression from first-line gemcitabine plus cisplatin, although treatment with modified FOLFOX (mFOLFOX) has been proven to be superior to active symptom control in the ABC-06 trial. Irinotecan (Camptosar) is an active drug used in the treatment of various gastrointestinal cancers.
ClarIDHy Phase 3 Study: IDH1 Mutation Detection in ctDNA and Clinical Response in Patients with Advanced Intrahepatic Cholangiocarcinoma
August 2020, Vol 1, No 1
Mutations in IDH1 are detected in approximately 13% of patients with intrahepatic cholangiocarcinoma (CCA). ClarIDHy was a global, phase 3, double-blind clinical trial in previously treated patients with advanced intrahepatic CCA with IDH1 mutation.

Subscribe to CCA News

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

I'd like to recieve: