The Lynx Group
Cholangiocarcinoma News

Drug Sensitivities Are Predicted with Tumor Organoid-Based Functional Analysis in Patients with Cholangiocarcinoma

2020 Year in Review: Cholangiocarcinoma — December 19, 2020

Patient-derived tumor organoids may have clinical application to predict drug responses in a personalized treatment setting; they have shown concordance with actionable genomic anchors and retrospective treatment outcomes.

Physicians now have a depth of information regarding molecular aberrations beyond the capacity of traditional DNA sequencing technologies because of analysis of next-generation sequencing. However, it has not led to treatment breakthroughs and is not providing treatment recommendations for many patients. Better predictive assays are needed to match the right drug with the right patient. At this year’s annual meeting of the American Association for Cancer Research, Astrid Margossian, MD, PhD, Chief Medical Officer, SEngine Precision Medicine, Seattle, WA, presented results of a new assay designed to address this issue.

A Clinical Laboratory Improvement Amendments (CLIA)-certified functional drug assay was developed by Dr Margossian and colleagues using patient-derived tumor organoids that can be applied for all solid tumors. The assay measures drug sensitivity and the personalization of response through the Sensory Processing Measure (SPM) score, providing an actionable report that outlines targeted therapies, endocrine treatments, and chemotherapy agents to help clinicians make therapeutic decisions.

Organoids are 3-dimensional structures derived from tumor tissue or tumor-specific stem cells that mimic tumor characteristics, including tumor-cell heterogeneity. Organoids unite many structural and functional aspects of their in vivo counterpart organs. Based on recent evidence, organoids have been shown to help predict drug responses accurately in a personalized treatment setting.

This study aimed to determine the concordance between organoid drug sensitivity measured by SPM score with genomic anchors from genomic reports. The study also aimed to examine the clinical correlation with previous treatments.

Taken for analysis were 19 samples from 17 patients aged 36 to 73 years (mean age, 51 years) with advanced or metastatic CCA. These samples included surgical, core biopsy, and fluids, such as ascites or pleural effusion. Organoid sensitivity was tested using the CLIA-certified functional drug assay to each drug in a library of <120 approved and investigational drugs. Response was quantified with an SPM score integrating drug sensitivity with response personalization using scores from 1 to 100; a higher score indicated a better response.

Fourteen of the 19 samples were screened successfully, and clinical and genomic data were captured for evaluation of 10 of the total 17 patients. Those patients who did not have a full clinical history and genomic profiling were not included in the analysis. There was an average of 71 drugs used per screening per patient, with the test identifying the top 7 scoring drugs per test. Test reports were completed in an average time of 17 days.

Presented in the poster was a case of a 44-year-old woman with stage IIIB multifocal intrahepatic CCA. Her disease progressed during 5 rounds of treatment, which included capecitabine, the FGFR inhibitor pemigatinib (Pemazyre), cisplatin plus gemcitabine, pressurized peritoneal aerosol chemotherapy with cisplatin and doxorubicin, and olaparib (Lynparza).

A paracentesis sample was obtained, and cultured organoids were developed and tested for 48 targeted drugs and chemotherapies for sensitivity. The drug assay verified the resistance to the previous regimens, but the test also showed sensitivities to histone deacetylase inhibitors, SRC kinase inhibitors, mTOR inhibitors, BRAF inhibitors, oxaliplatin, and the multikinase inhibitor midostaurin (Rydapt). Remission was reached in this patient for 4 months when she received dasatinib (Sprycel, an SRC kinase inhibitor).

According to Dr Margossian and colleagues, 87% of the samples had good concordance with actionable genomic anchors and 100% concordance with retrospective treatments based on test results. In addition, concordance with prospective treatment response was achieved by 3 patients in the study.

According to Dr Margossian in an interview with CCA News, “This is a revolutionary approach that helps the oncologist in ‘everyday’ therapeutic decisions. The strong correlation of organoid drug response to previous treatment outcomes demonstrates the predictive power of our test. This innovative technique determines organoid sensitivity or resistance to oncology treatments, with a clear benefit for patients in time and toxicity.”

Source: Margossian A, et al. Cancer Res. 2020;80(16_suppl). Abstract 818.

Related Items

Ivosidenib Approved for Advanced or Metastatic Cholangiocarcinoma
Web Exclusives
Ivosidenib has been approved by the FDA for adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 mutation as detected by an FDA-approved test.
Recent Developments in Genomic-Driven Therapies for Cholangiocarcinoma
June/July 2021, Vol 2, No 2
Personalized medicine has expanded the treatment options for patients with cholangiocarcinoma (CCA). At the 2021 Annual Meeting of the Cholangiocarcinoma Foundation (CCF), Ghassan K. Abou-Alfa, MD, MBA, Professor of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, discussed recent developments in personalized therapies, highlighting genomic alterations that are informing the new therapies for patients with CCA.
FDA Grants Accelerated Approval to Infigratinib for Metastatic Cholangiocarcinoma
June/July 2021, Vol 2, No 2
The FDA granted accelerated approval to the kinase inhibitor infigratinib (Truseltiq) for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) that harbors an FGFR2 fusion or other rearrangement.
Futibatinib in Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Rearrangements: Primary Results of FOENIX-CCA2 Presented at AACR 2021
June/July 2021, Vol 2, No 2
The primary results of the phase 2 FOENIX-CCA2 clinical trial of futibatinib in patients with previously treated intrahepatic cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements were presented by Lipika Goyal, MD, MPhil, Assistant Professor of Medicine, Massachusetts General Hospital, Boston, at the 2021 Annual Meeting of the American Association for Cancer Research (AACR).
Truseltiq (Infigratinib) New Targeted Therapy FDA Approved for Advanced or Metastatic Cholangiocarcinoma Harboring FGFR2 Alterations
By Loretta Fala
June/July 2021, Vol 2, No 2
Cholangiocarcinoma (CCA) represents a group of heterogeneous cancers that originate in the bile ducts that connect the liver and gallbladder to the small intestine. Although the exact prevalence of CCA is unknown, CCA is a rare cancer; approximately 8000 new cases of CCA are diagnosed annually in the United States.
Incorporating FGFR Inhibitors into the Treatment Paradigm for Cholangiocarcinoma: Current Concepts and Future Directions
By Mitesh J. Borad, MD; Milind M. Javle, MD; Michael Morse, MD, FACP, MHS; Lewis R. Roberts, MB, ChB, PhD
June/July 2021, Vol 2, No 2
On January 15, 2021, experts in the management of patients with cholangiocarcinoma (CCA) convened for a virtual accredited continuing education satellite symposium held during the 2021 annual meeting of the American Society of Clinical Oncology Gastrointestinal Cancers Symposium. The goal was to educate healthcare providers on various aspects of CCA, including epidemiology, current standards of care, unmet clinical needs, the safety and efficacy of fibroblast growth factor receptor (FGFR) inhibitors as second-line therapy, and practical approaches to incorporating FGFR inhibitors into the treatment paradigm for the disease.
The Latest Research in Biliary Tract Cancers Presented at ASCO GI 2021
March 2021, Vol 2, No 1
At the CCA Summit held during the 2021 ASCO Gastrointestinal (GI) Cancers Symposium, Rachna T. Shroff, MD, MS, Chief, Section of GI Medical Oncology, University of Arizona Cancer Center, Tucson, discussed 15 clinical trials that were presented at the ASCO GI Cancers Symposium on cholangiocarcinoma (CCA) and hepatobiliary diseases. She highlighted key advances related to chemotherapy, targeted therapies, and biomarkers in the management of biliary tract cancers, including CCA.
Targeted Therapies in Cholangiocarcinoma: Next-Generation Sequencing Is a Must
December 2020, Vol 1, No 3
The recent FDA approval of the first FGFR inhibitor, pemigatinib (Pemazyre), and the positive results from the phase 3 study of the first IDH1 inhibitor, ivosidenib (Tibsovo), represent major breakthroughs in the treatment of patients with cholangiocarcinoma (CCA), a rare cancer associated with poor outcomes. However, the duration of response with these agents is still relatively short.
FGFR Inhibition in Cholangiocarcinoma: Overcoming Acquired Resistance
December 2020, Vol 1, No 3
In April 2020, the FDA granted accelerated approval to pemigatinib (Pemazyre), the first targeted therapy for cholangiocarcinoma (CCA). The FGFR inhibitor was approved for adults with CCA and FGFR2 fusion.
Emerging Molecular Targets in Cholangiocarcinoma: IDH1, HER2, BRAF, and Beyond
December 2020, Vol 1, No 3
Targeted therapy has improved survival for patients with cancer across a broad spectrum of disease sites, but until recently, progress has been slow in the treatment of patients with cholangiocarcinoma (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: