The Lynx Group
Interview with the Innovators
NTRK Gene Fusion Enrichment in Patient Subpopulations
Dr Ezra Cohen of UC San Diego, La Jolla, CA, and Dr Arturo Loaiza-Bonilla of the Comprehensive Care and Research Center, Philadelphia, PA, identify specific subpopulations of patients in which NTRK gene fusions may be commonly uncovered.
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Occurrence of TRK Fusion–Positive Tumors in Different Cancer Types
Dr Ezra Cohen of UC San Diego, La Jolla, CA; Dr Mary Fidler of Rush University Medical Center, Chicago, IL; and Dr Arturo Loaiza-Bonilla of the Comprehensive Care and Research Center, Philadelphia, PA, confer on the categorization of various cancer types in which NTRK gene fusions may be detected.
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Significance of Early and Broad Testing of Tumor Mutations
Dr Ezra Cohen of UC San Diego, La Jolla, CA; Dr Mary Fidler of Rush University Medical Center, Chicago, IL; and Dr Arturo Loaiza-Bonilla of the Comprehensive Care and Research Center, Philadelphia, PA, discuss how testing for tumor mutations early and broadly may lead to better treatment outcomes.
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Who Should Be Screened for Tumor Mutations?
Dr Ezra Cohen of UC San Diego, La Jolla, CA; Dr Mary Fidler of Rush University Medical Center, Chicago, IL; and Dr Arturo Loaiza-Bonilla of the Comprehensive Care and Research Center, Philadelphia, PA, examine who should be tested for tumor mutations.
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Using FGFR Inhibitors in Clinical Practice
Dr Angela Lamarca discusses the use of FGFR inhibitors in daily practice. Their use will depend largely on data from currently ongoing second- and first-line clinical trials. She suggests that consideration should be given to their use in combination with chemotherapy and/or as maintenance therapy after first-line chemotherapy. Dr Milind Javle summarizes the field, suggesting that a time may come when patients with CCA are never treated with chemotherapy at all. Pemigatinib was FDA approved as second-line therapy in cholangiocarcinoma in May 2020.
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Toxicities Associated with FGFR Inhibitors
Dr Vaibhav Sahai reviews the toxicities that have been encountered in clinical trials with FGFR inhibitors. He suggests that most of these adverse events are class effects and include hyperphosphatemia (which is relatively easy to manage with dietary restrictions and phosphate-binding agents), nail and hair changes, stomatitis, and retinal epithelial changes. In contrast, Dr Angela LaMarca considers the adverse events associated with chemotherapy, including myelosuppression, nausea, vomiting, diarrhea, and others. Dr Milind Javle suggests that the toxicities encountered with chemotherapy are significantly worse than those with FGFR inhibitors.
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Effective Targeted Therapies in CCA: IDH1 and FGFR
Dr Angela Lamarca reviews the current clinical trials with FGFR inhibitors, particularly those with patients with FGFR2 fusion and other genetic aberrations. Dr Vaibhav Sahai highlights those FGFR inhibitors that are nonselective and those that are selective for FGFR1-4, and discusses the clinical trial results with the selective inhibitors, including pemigatinib and infigratinib. He remarks that the response rates and progression-free survival in these trials have been remarkable, far better than what is seen with chemotherapy.
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Managing CCA Patients While Waiting for Molecular Biomarker Testing Results
Dr Vaibhav Sahai and Dr Angela Lamarca consider options for managing patients with CCA while awaiting results from biomarker testing, which can take 3 to 6 weeks. They discuss starting these patients on first-line chemotherapy and then switching appropriate patients to second-line targeted therapy, and also speak to the increased utility of next-generation sequencing in CCA.
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The Use of Molecular Biomarker Testing in Patients with CCA
Dr Vaibhav Sahai discusses different approaches to molecular biomarker testing, including when to order the tests in the course of the disease, use of institutional and commercial testing facilities, and what platforms exist for testing.
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Current Approaches to Treatment of Advanced CCA
Dr Angela Lamarca discusses approaches to first- and second-line therapy for patients with advanced CCA.
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