Abstract 300P
Background
FGFR2 and IDH1 status are key determinants of treatment choice in pretreated patients (pts) with aBTC, due to tailored drug availability and access to clinical trials. While waiting for the results of ongoing first-line trials with targeted therapies (TT), whether FGFR2 and IDH1 alterations impact the sensitivity to standard platinum-based first-line chemotherapy (CT1) remains an open issue. Here we queried the ANITA database intending to describe FGFR2 and IDH1 prognostic role for pts with aBTC and their putative predictive significance to standard CT1.
Methods
ANITA is an observational study, enrolling 621 pts with BTC treated at 10 tertiary Italian cancer centers between 2017 and 2023. The prognostic role of FGFR2 fusions/rearrangements and IDH1 R132 mutation was tested for overall survival (OS, calculated since the first cycle of CT1), excluding pts who received TT (i.e. FGFR2 or IDH1 inhibitors) in any line. The predictive role for platinum-based CT1 was tested for progression-free survival (PFS). Kaplan Meier curves and Cox regression model were generated.
Results
Thirty-four pts with FGFR2-fused/rearranged disease and 45 pts with IDH1-mutated tumors (97% and 95% diagnosed with intrahepatic aBTC, respectively) were identified and included in the analyses. No predictive role for platinum-based CT1 PFS was found for either FGFR2 (p=0.928) or IDH1 (p=0.945) alterations. No association with OS was reported for IDH1 status (p=0.885). At univariate analysis, FGFR2 alterations demonstrated a positive correlation with OS (HR 0.49, 95%CI 0.33-0.74, p=0.005). Among other clinical characteristics, higher (>500 UI/L) CA19-9 levels before CT1, liver metastases, [LR1] synchronous metastatic disease and multiple sites of metastases negatively affected OS. At multivariate analysis, only baseline CA19-9 levels retained statistical significance (p=0.037).
Conclusions
In our case series, FGFR2 or IDH1 targetable alterations do not seem to represent independent prognostic factors in aBTC, nor to confer differential sensitivity to platinum-based standard CT1. Further observation on immunotherapy-comprising first-line regimens is needed to confirm our results.
Legal entity responsible for the study
Fondazione GONO.
Funding
AstraZeneca.
Disclosure
F. Nichetti: Financial Interests, Personal, Invited Speaker: AstraZeneca. L. Salvatore: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Servier, Bayer, Merck, Amgen, Pierre Fabre, GSK, Takeda, Incyte; Financial Interests, Personal, Advisory Role: MSD, AstraZeneca, Servier, Bayer, Merck, Amgen, Pierre Fabre, GSK, Takeda, Incyte. L. Antonuzzo: Financial Interests, Personal, Invited Speaker, Institutional research funding: AstraZeneca, Novartis; Financial Interests, Personal, Invited Speaker: Roche, Astellas, MSD, BMS, Ipsen, Merk, Amgen, Bayer. G. Masi: Financial Interests, Personal, Advisory Role: AstraZeneca, Eisai, MSD, Roche; Financial Interests, Institutional, Sponsor/Funding: Terumo. L. Rimassa: Financial Interests, Personal, Advisory Board, Consulting and advisory role: AbbVie, AstraZeneca, Basilea, Bayer, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, Bayer, BMS, Incyte, Ipsen, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche, Servier, Agios, Eisai, FibroGen, Lilly, MSD, Roche, Servier; Financial Interests, Institutional, Invited Speaker, National (Italian) coordinating PI: AstraZeneca, BeiGene, Zymeworks; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Invited Speaker, European PI: AstraZeneca; Non-Financial Interests, Leadership Role, Treasurer: ILCA; Non-Financial Interests, Leadership Role, Co-chair: EORTC GITCG HB/NET Task Force; Non-Financial Interests, Other, Special Expert Clinical Trials Europe: NCI HB Task Force. L. Fornaro: Financial Interests, Personal, Invited Speaker, Advisory role: Lilli, MSD, Servier; Financial Interests, Personal, Invited Speaker, Advisory role, Institutional funding: Incyte; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Role, Institutional funding: AstraZeneca/Daiichi Sankyo, Astellas Pharma; Financial Interests, Personal, Advisory Role: Tahio Pharmaceutical; Financial Interests, Institutional, Funding: Merck Sharp & Dohme, Janssen, Nucana, AstraZeneca/Daiichi Sankyo, Roche, BeiGene. All other authors have declared no conflicts of interest.