GRCh38 · COSMIC v98


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Clinicogenomic Analysis of FGFR2-Rearranged Cholangiocarcinoma Identifies Correlates of Response and Mechanisms of Resistance to Pemigatinib.
Paper ID
Silverman IM, Hollebecque A, Friboulet L, Owens S, Newton RC, Zhen H, Féliz L, Zecchetto C, Melisi D and Burn TC
Incyte Research Institute, Wilmington, Delaware.
Cancer discovery, 2021;11(2):326-339
ISSN: 2159-8290
PMID: 33218975 (view at PubMed or Europe PMC)
Pemigatinib, a selective FGFR1-3 inhibitor, has demonstrated antitumor activity in FIGHT-202, a phase II study in patients with cholangiocarcinoma harboring <i>FGFR2</i> 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 <i>FGFR2</i> 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 <i>FGFR2</i>. Clinicogenomic analysis of pemigatinib-treated patients identified mechanisms of primary and acquired resistance. Genomic subsets of patients with other potentially actionable <i>FGF/FGFR</i> 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 cholangiocarcinoma, to understand the molecular diversity of patients with <i>FGFR2</i> fusions or rearrangements, and to interrogate the clinicogenomics of patients treated with pemigatinib. Our study highlights the utility of genomic profiling in clinical trials.<i>This article is highlighted in the In This Issue feature, p. 211</i>.
Paper Status