Cholangiocarcinoma With <i>FGFR</i> Genetic Aberrations: A Unique Clinical Phenotype.
case_control · Level III
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- Record sourced from PubMed, PMID 35135097.
- Also identified by DOI 10.1200/PO.17.00080.
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Abstract
<i>FGFR</i> genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with <i>FGFR</i> GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown. Patients with CCA with <i>FGFR</i> GAs were identified using next-generation sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with <i>FGFR</i> wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher's exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis. Three hundred seventy-seven patients with CCA were identified, and 95 had <i>FGFR</i> GAs. <i>FGFR2</i> GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, <i>FGFR</i> GAs occurred more frequently in younger patients (≤ 40 years; 20%) compared with older patients (> 40 years; 6.7%; <i>P</i> < .001), presented at an earlier stage (TNM stage I/II <i>v</i> III/IV: 35.8% <i>v</i> 22%, respectively; <i>P</i> = .001), and were associated with a longer OS compared with patients without <i>FGFR</i> GAs (37 <i>v</i> 20 months, respectively; <i>P</i> < .001). This difference remained significant after excluding 36 patients treated with FGFR inhibitors. There was no OS difference (<i>P</i> = .60) between CCA with <i>FGFR2</i> fusions (n = 63) versus other <i>FGFR</i> GAs (n = 29). Patients with <i>FGFR</i> GAs had a better OS with FGFR-targeted therapy compared with standard treatment (<i>P</i> = .01). <i>BAP1</i> mutation was the most common coexisting mutation without prognostic impact, whereas <i>TP53</i> (<i>P</i> = .04) and <i>CDKN2A/B</i> (<i>P</i> = .04) were correlated with a shorter OS. CCA with <i>FGFR</i> GAs represents a unique subtype occurring in younger patients with an indolent disease course. FGFR-targeted therapy may have a positive impact on OS in this subgroup.