iCCA is a genomically diverse disease where various genomic alterations have been identified. FGFR2 fusions are present in up to 15% of iCCA tumors and are drivers that result in activation of the FGFR pathway. While early studies implicate their potential as a therapeutic target, thier impact on the natural course of the disease is unknown. Herein, we describe the natural history iCCA FGFR2 fusions, its prognostic role and utility for FGFR-targeted therapy.
A multi-center, retrospective analysis was performed, where we identified pts with advanced iCCA. FGFR2 fusions were detected by using a CLIA certified next generation sequencing panel or fluorescence in situ hybridization. We assessed pt outcomes with advanced iCCA whose tumors were identified as having FGFR2 fusions compared to those that did not exhibit FGFR2 fusions. Univariate Cox regression model was used to determine the association between gene alterations with progression free survival (PFS) and (OS).
One hundred thirty-five pts with advanced iCCA were identified, with forty-five having FGFR2 fusions. In patients with iCCA, FGF2R fusions appeared to occur at a younger age (55 v 58 yrs; p = 0.1919) compared to the control but was not signficant. Ethnicity (p = 0.5162), gender (p = 0.4967), differentiation (p = 0.7754) were evaluated and were not significantly different between groups iCCA FGFR2 fusions pts were more likely to be diagnosed with advanced disease, stage IIIB or greater (p = 0.0016). No significant differences in PFS were observed from gemcitabine-platinum based chemotherapy in pts whose tumors exhibited FGFR2 fusions (0.5 v 0.5 yrs, HR 1.19, P = 0.36). An significant median OS was observed in pts whose tumors exhibited FGFR2 fusions compared to those that were WT for FGFR2 fusions (2.7 vs 1.3 yrs, HR 0.44, p = 0.002).
Somatic FGFR2 fusions were associated with a significant survival advantage in pts with advanced iCCA. FGFR2 fusions may also be prognostic to chemotherapy response. FGFR is a therapeutic target of interest, where future prospective studies will be necessary to validate the predictive, prognostic utility and its relevance in pt outcomes in iCCA.
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All authors have declared no conflicts of interest.