Clinicogenomic Analysis of FGFR2-Rearranged Cholangiocarcinoma Identifies Correlates of Response and Mechanisms of Resistance to Pemigatinib.

Cancer Discovery
Ian M SilvermanTimothy C Burn

Abstract

Pemigatinib, a selective FGFR1-3 inhibitor, has demonstrated antitumor activity in FIGHT-202, a phase II study in patients with cholangiocarcinoma harboring FGFR2 fusions/rearrangements, and has gained regulatory approval in the United States. Eligibility for FIGHT-202 was assessed using genomic profiling; here, these data were utilized to characterize the genomic landscape of cholangiocarcinoma and to uncover unique molecular features of patients harboring FGFR2 rearrangements. The results highlight the high percentage of patients with cholangiocarcinoma harboring potentially actionable genomic alterations and the diversity in gene partners that rearrange with FGFR2. Clinicogenomic analysis of pemigatinib-treated patients identified mechanisms of primary and acquired resistance. Genomic subsets of patients with other potentially actionable FGF/FGFR alterations were also identified. Our study provides a framework for molecularly guided clinical trials and underscores the importance of genomic profiling to enable a deeper understanding of the molecular basis for response and nonresponse to targeted therapy. SIGNIFICANCE: We utilized genomic profiling data from FIGHT-202 to gain insights into the genomic landscape of cholangiocar...Continue Reading

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Mar 19, 2021·Cancer Treatment Reviews·Lipika GoyalJohn Bridgewater
Mar 18, 2021·The New England Journal of Medicine·Lipika GoyalVikram Deshpande
Mar 21, 2021·Journal of Hepatology·Giulia CristinzianoOreste Segatto
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Oct 1, 2021·Expert Review of Clinical Pharmacology·Matteo RepettoGiuseppe Curigliano
Oct 27, 2021·Expert Opinion on Investigational Drugs·Stephan BraunMarc Engelhardt

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