Abstract 4843
Background
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.
Methods
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).
Results
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).
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Daniel Ahn.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3278 - Immune-Related Gene Expression Profiling after Neoadjuvant Chemotherapy (NACT) of Ovarian High-Grade Serous Carcinoma
Presenter: Luis Manso
Session: Poster Display session 2
Resources:
Abstract
4906 - Tumor-infiltrating lymphocytes (TILs) in patients with epithelial ovarian cancer undergoing neoadjuvant chemotherapy: A restrospective study
Presenter: Sara Giovannoni
Session: Poster Display session 2
Resources:
Abstract
3919 - Prognostic significance of elements of the adaptive immunity in the microenvironment of epithelial ovarian cancer.
Presenter: Periklis Foukas
Session: Poster Display session 2
Resources:
Abstract
5139 - Neutrophil-to-lymphocyte ratio predicts platinum sensitivity in epithelial ovarian cancer patients: a MITO24 retrospective study
Presenter: Alberto Farolfi
Session: Poster Display session 2
Resources:
Abstract
4212 - The prognostic impact of monocyte to lymphocyte ratio (MLR) in advanced epithelial ovarian cancer (EOC)
Presenter: Marc Cucurull Salamero
Session: Poster Display session 2
Resources:
Abstract
5123 - TP53 Hotspot mutations as immunoreactive neoantigens define a signature with differential survival outcomes in advanced ovarian cancer
Presenter: Marica Garziera
Session: Poster Display session 2
Resources:
Abstract
3795 - Use of bevacizumab (Bev) in real life for first-line (fl) treatment of ovarian cancer (OC)/ The GINECO ENCOURAGE cohort of 500 French patients
Presenter: Dominique Berton-Rigaud
Session: Poster Display session 2
Resources:
Abstract
2359 - Phase II study: Letrozole maintenance therapy after first line chemotherapy in patients with advanced serous and endometrioid ovarian cancer
Presenter: Alexandra Tyulyandina
Session: Poster Display session 2
Resources:
Abstract
3619 - Baseline IPI (Immune Prognostic Index) predicts survival in patients with advanced cervical cancer treated with immune checkpoint inhibitors (ICI).
Presenter: Felix Blanc-Durand
Session: Poster Display session 2
Resources:
Abstract
3474 - Preselecting tumor-infiltrating lymphocyte subsets to implement adoptive inmmunotherapy in ovarian cancer
Presenter: Diego Salas-Benito
Session: Poster Display session 2
Resources:
Abstract