Abstract 303P
Background
BTC have a poor prognosis with limited treatment options. This is coupled with a poor understanding of the biological background. Extensive genetic profiling allowed to distinguish different molecular entities. The incidence and the prognostic role of these molecular features have not been fully elucidated.
Methods
This is a retrospective study conducted at Istituto Oncologico Veneto in Padua in which we expanded our previous dataset focusing on patients with diagnosis of advanced/metastatic intrahepatic cholangiocarcinoma. All consecutive patients with availability of tissue samples were considered eligible. Targeted alterations included: FGFR2/3 aberrations, IDH1/2 mutations, HER2 alterations, BRAF alterations, NTRK alterations and mismatch repair proteins deficiency (MMRd). These alterations were identified by means of immunohistochemistry, RT-PCR, next-generation sequencing, and fluorescence in situ hybridization.
Results
A total of 247 patients were enrolled. Twenty-three patients (9.3%) presented FGFR2 fusions/amplifications (F2F). IDH1/2 resulted mutated in 50 patients (20.2%). A total of 18 patients (7.3%) had a HER2 gene alteration, 9 patients (3.6%) had a BRAF gene alteration, 3 patients (1.2%) NTRK1 amplifications and 6 patients (2.4%) had a MMR deficit. Patients F2F had a lower risk of death compared to wild type patients (F2N) (HR 0.48, 95% CI 0.28 - 0.80, p = 0.005). F2F had a median overall survival (OS) of 24.5 months (95% CI 19.4 – NA) compared to 15.7 months (95% CI 13.4 – 18.6) of F2N patients. Fourteen patients received anti-FGFR2 drugs, censoring these patients from the survival analysis still maintains an advantage in OS for F2F patients (HR 0.23, 95%CI 0.10 – 0.52, p < 0.001). This advantage in OS was maintained also at multivariate analysis (p = 0.009).
Conclusions
Our data provide a strong proof - challenged with a robust and detailed multivariate model - that FGFR2 alterations can be prognostic for better survival. Our data should be considered in the design of new trials, for example as adjusting or stratification factors in prospective clinical studies.
Legal entity responsible for the study
The authors.
Funding
QED Therapeutics (San Francisco, CA), Italian Health Ministry and Veneto Region research program NET-2016-02363853, Italian Association for Cancer Research AIRC under the 5 per Mille 2019 program (ID No. 22759).
Disclosure
M.D. Rizzato: Financial Interests, Invited Speaker: AstraZeneca. C. Soldà: Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Advisory Board: Roche, Eisai. S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, Lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi Sankyo, Bristol Myers Squibb, Astellas, GSK, Takeda, Bayer; Financial Interests, Personal, Invited Speaker: Pierre Fabre, GSK, Roche, Servier, Amgen, Bristol Myers Squibb, Incyte, Lilly, Merck Serono, MSD; Financial Interests, Institutional, Invited Speaker: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol Myers Squibb; Non-Financial Interests, Member of Board of Directors, Italian No-Profit Oncology Research Foundation supporting academic Clinical trials: GONOFoundation. F. Bergamo: Financial Interests, Personal, Invited Speaker: Lilly, BMS, MSD, Eisai, Bayer, Amgen; Financial Interests, Personal, Advisory Board: Servier, AAA; Other, congress: Bayer, Ipsen, AAA. M. Fassan: Financial Interests, Advisory Role: Astellas Pharma, Pierre Fabre, MSD, AstraZeneca, Janssen, GSK, BMS, Incyte, Amgen, Lilly, Novartis, Roche; Financial Interests, Funding: Astellas Pharma, QED Therapeutics, Diaceutics, Macrophage Pharma. All other authors have declared no conflicts of interest.