Validation and Characterization of FGFR2 Rearrangements in Cholangiocarcinoma with Comprehensive Genomic Profiling.

Autor:	Silverman IM; Translational Sciences, Incyte Research Institute, Wilmington, Delaware., Li M; Research and Development, Foundation Medicine, Cambridge, Massachusetts., Murugesan K; Research and Development, Foundation Medicine, Cambridge, Massachusetts., Krook MA; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Javle MM; University of Texas MD Anderson Cancer Center, Houston, Texas., Kelley RK; University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, California., Borad MJ; Mayo Clinic Cancer Center, Scottsdale, Arizona., Roychowdhury S; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Meng W; Research and Development, Foundation Medicine, Cambridge, Massachusetts., Yilmazel B; Research and Development, Foundation Medicine, Cambridge, Massachusetts., Milbury C; Research and Development, Foundation Medicine, Cambridge, Massachusetts., Shewale S; Research and Development, Foundation Medicine, Cambridge, Massachusetts., Feliz L; Clinical Development, Incyte Biosciences International Sàrl, Morges, Switzerland., Burn TC; Translational Sciences, Incyte Research Institute, Wilmington, Delaware. Electronic address: tburn@tyra.bio., Albacker LA; Research and Development, Foundation Medicine, Cambridge, Massachusetts. Electronic address: lalbacker@foundationmedicine.com.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2022 Apr; Vol. 24 (4), pp. 351-364. Date of Electronic Publication: 2022 Feb 14.
DOI:	10.1016/j.jmoldx.2021.12.012
Abstrakt:	Cholangiocarcinoma (CCA) is a heterogeneous biliary tract cancer with a poor prognosis. Approximately 30% to 50% of patients harbor actionable alterations, including FGFR2 rearrangements. Pemigatinib, a potent, selective fibroblast growth factor receptor (FGFR) FGFR1-3 inhibitor, is approved for previously treated, unresectable, locally advanced or metastatic CCA harboring FGFR2 fusions/rearrangements, as detected by a US Food and Drug Administration-approved test. The next-generation sequencing (NGS)-based FoundationOneCDx (F1CDx) was US Food and Drug Administration approved for detecting FGFR2 fusions or rearrangements. The precision and reproducibility of F1CDx in detecting FGFR2 rearrangements in CCA were examined. Analytical concordance between F1CDx and an externally validated RNA-based NGS (evNGS) test was performed. Identification of FGFR2 rearrangements in the screening population from the pivotal FIGHT-202 study (NCT02924376) was compared with F1CDx. The reproducibility and repeatability of F1CDx were 90% to 100%. Adjusted positive, negative, and overall percentage agreements were 87.1%, 99.6%, and 98.3%, respectively, between F1CDx and evNGS. Compared with evNGS, F1CDx had a positive predictive value of 96.2% and a negative predictive value of 98.5%. The positive percentage agreement, negative percentage agreement, overall percentage agreement, positive predictive value, and negative predictive value were 100% for F1CDx versus the FIbroblast Growth factor receptor inhibitor in oncology and Hematology Trial-202 (FIGHT-202) clinical trial assay. Of 6802 CCA samples interrogated, 9.2% had FGFR2 rearrangements. Cell lines expressing diverse FGFR2 fusions were sensitive to pemigatinib. F1CDx demonstrated sensitivity, reproducibility, and high concordance with clinical utility in identifying patients with FGFR2 rearrangements who may benefit from pemigatinib treatment. (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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