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
2670 - Molecular subtypes of metastatic(met) gastric cancer(GC) (MoTriGastric): new biomarkers closer to the clinics
Presenter: Maria Alsina Maqueda
Session: Poster Display session 2
Resources:
Abstract
3797 - Exploring candidate signal transduction pathways for targeted therapy in esophageal cancer
Presenter: Aafke Creemers
Session: Poster Display session 2
Resources:
Abstract
5485 - Clinical implication of CLDN18, RhoGAP, and E-cadherin in gastric signet ring cell carcinoma
Presenter: Hyunho Kim
Session: Poster Display session 2
Resources:
Abstract
1970 - Identification of a spectrum of germline mutations for hereditary diffuse gastric cancer in the Russian population by next-generation sequencing.
Presenter: IRINA EFIMOVA
Session: Poster Display session 2
Resources:
Abstract
4989 - The molecular profiling and prognostic value of Chinese gastric signet ring cell carcinoma patients
Presenter: Jia Wei
Session: Poster Display session 2
Resources:
Abstract
7145 - A phase 2 basket study of MCLA-128, a bispecific antibody targeting the HER3 pathway, in NRG1 fusion-positive advanced solid tumors
Presenter: Alison Schram
Session: Poster Display session 2
Resources:
Abstract
1406 - Simultaneous Resection of Pancreatic Cancer and Liver Oligometastases After Induction Chemotherapy in Stage IV Patients:an Open-Label Prospective Randomized Multicenter phase 3 trial(CSPAC-1)
Presenter: Miaoyan Wei
Session: Poster Display session 2
Resources:
Abstract
1530 - Multicenter randomized phase II trial of 5-Fluorouracil/leucovorin (5-FU/LV) with or without liposomal irinotecan (nal-IRI) in metastatic biliary tract cancer (BTC) as second-line therapy after progression on gemcitabine plus cisplatin (GemCis): NIFTY trial
Presenter: Changhoon Yoo
Session: Poster Display session 2
Resources:
Abstract
1563 - A randomized phase II study of Maintenance therapy with multiepitope vaccine Tedopi (OSE2101) ± nivolumab or FOLFIRI after induction chemotherapy (CT) with FOLFIRINOX in patients (Pts) with advanced Pancreatic ductal adenocarcinoma (aPDAC) (TEDOPaM – PRODIGE 63 GERCOR study)
Presenter: Cindy Neuzillet
Session: Poster Display session 2
Resources:
Abstract
2780 - A phase 3, randomized, double-blind, placebo-controlled, international study of durvalumab in combination with gemcitabine plus cisplatin for patients with advanced biliary tract cancers: TOPAZ-1
Presenter: Do-Youn Oh
Session: Poster Display session 2
Resources:
Abstract