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
1902 - Phase II trial of preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by postoperative gemcitabine (GEM) in patients (pts) with borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)
Presenter: Jae Ho Jeong
Session: Poster Display session 2
Resources:
Abstract
3716 - Prognostic factors for predicting early recurrence within the first year of surgery in pancreatic ductal adenocarcinoma
Presenter: Naru Kim
Session: Poster Display session 2
Resources:
Abstract
3947 - Integrated population pharmacokinetic modelling of liposomal irinotecan in patients with various tumour types, including untreated metastatic pancreatic cancer (mPC)
Presenter: Teresa Macarulla
Session: Poster Display session 2
Resources:
Abstract
2880 - Expression of long noncoding RNA and clinical outcomes of pancreatic cancer patients who received adjuvant chemotherapy by S-1 or GEM after curative resection.
Presenter: Mariko Kamiya
Session: Poster Display session 2
Resources:
Abstract
5029 - POLO: Time to treatment discontinuation and subsequent therapies following maintenance olaparib for patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC)
Presenter: Eric Van Cutsem
Session: Poster Display session 2
Resources:
Abstract
4730 - Diagnostic Value of Digital Multiplexed Detection of Single Nucleotide Variants in Pancreatic Cancer Specimens Collected by Endoscopic Ultrasound Fine-Needle Aspiration
Presenter: Irina Cazacu
Session: Poster Display session 2
Resources:
Abstract
3303 - Phase I/II study of LDE225 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer
Presenter: Esther Pijnappel
Session: Poster Display session 2
Resources:
Abstract
2009 - Efficacy of platinum-containing chemotherapy and prognosis of pancreatic cancer patients with homologous recombination deficiency: meta-analysis of published clinical studies
Presenter: Elizeveta Polyanskaya
Session: Poster Display session 2
Resources:
Abstract
2164 - Plasmatic CXCL8 is a marker for TGFß-activated kinase 1 (TAK1) activation which may predict resistance to nanoliposomal irinotecan (nal-IRI) in gemcitabine-refractory pancreatic cancer (PC) patients
Presenter: Valeria Merz
Session: Poster Display session 2
Resources:
Abstract
2529 - A protein level signature of four selected genes associated with survival outcomes of patients with pancreatic ductal adenocarcinoma
Presenter: Jie Hua
Session: Poster Display session 2
Resources:
Abstract