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
5134 - Early prediction of the platinum-resistant relapse risk using the CA125 modeled kinetic parameter KELIM: a pooled analysis of AGO-OVAR 7 & 9; ICON 7 (AGO/GINECO/ MRC CTU/GCIG trials).
Presenter: OLIVIER COLOMBAN
Session: Poster Display session 2
Resources:
Abstract
4410 - Mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), in combination with carboplatin and bevacizumab: Initial results from a Phase 1b study in patients (pts) with ovarian cancer
Presenter: David Omalley
Session: Poster Display session 2
Resources:
Abstract
5077 - Response to Pegylated Liposomal Doxorubicin (PLD) and Weekly Paclitaxel (wpac) in Platinum Resistant (PR) Ovarian Cancer (OC) by BRCA mutation status
Presenter: Louise Bremer
Session: Poster Display session 2
Resources:
Abstract
3483 - Impact of prior pegylated liposomal doxorubicin (PLD) treatment in recurrent ovarian cancer (ROC): Sub-group analysis from a randomized, open-label study comparing trabectedin (T) and PLD versus PLD alone in ROC (ET743-OVC-3006)
Presenter: Bradley Monk
Session: Poster Display session 2
Resources:
Abstract
5423 - OCTAVE - A phase I study of enadenotucirev, an oncolytic group B adenovirus, in combination with weekly paclitaxel in platinum-resistant epithelial ovarian cancer
Presenter: Iain McNeish
Session: Poster Display session 2
Resources:
Abstract
1385 - Phase I study of low dose whole abdominal radiation therapy (LDWART) in combination with weekly paclitaxel (wP) for platinum resistant ovarian cancer (PROC)
Presenter: Natalie Ngoi
Session: Poster Display session 2
Resources:
Abstract
2090 - Phase 1b/2a study assessing the safety and efficacy of adding AL3818 (Anlotinib) to standard platinum-based chemotherapy in subjects with recurrent or metastatic endometrial, ovarian or cervical carcinoma
Presenter: David Miller
Session: Poster Display session 2
Resources:
Abstract
1960 - Phase I Study of Intraperitoneal TRX-E-002-1 in Subjects with Persistent or Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer: Three-month Follow-up Results of the Dose Escalation Phase
Presenter: Jermaine Coward
Session: Poster Display session 2
Resources:
Abstract
4288 - Hybrid capture-based genomic profiling of circulating tumor DNA (ctDNA) from patients with ovarian cancer
Presenter: Mi Yang
Session: Poster Display session 2
Resources:
Abstract
3433 - Tumor Microvessel Density for predicting Nintedanib activity: data from the randomized CHIVA trial (a GINECO study)
Presenter: Maud Villemin
Session: Poster Display session 2
Resources:
Abstract