108P - FGFR2 fusions and their impact on efficacy of standard chemotherapy in patients with biliary tract cancer

Background

The incidence of biliary tract cancer (BTC) is increasing globally, while its survival remains dismal. FGFR2 fusions offer a potential therapeutic option with oral inhibitors, although the optimal treatment sequence for these patients remains unclear.

Methods

We included patients from all three Mayo Clinic sites diagnosed with FGFR2 fusion-positive (F2P) BTC and used patients with FGFR2 fusion-negative (F2FN) BTC as historical controls. We estimated overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier techniques.

Results

We identified 43 F2P and 155 F2FN patients with BTC. The most common gene fusion partner was BICC1 (28%). FGFR2 fusion was associated with age ≤65 years (74% vs 44%), female gender (72% vs 45%), intrahepatic BTC (95% vs 71%), and advanced stage at diagnosis (60% vs 11%). In advanced disease, 25 patients in the F2P group received first-line (1L) chemo of which 14 (56%) received gemcitabine/cisplatin (GC). In the F2FN group, 37 had 1L chemo, 16 (43%) with GC. The F2P group had significantly lower PFS compared to F2FN patients, respective median PFS were 5.4 (95% CI 3.8-9) vs 7.6 months (95% CI 4.6-13.3) (p=0.038). In the F2P group who received second-line (2L) therapy, PFS was longer with an FGFR inhibitor (8.2 months, 95% CI 7.2-NE) vs. chemo (5.5 months, 95% CI 4.8-19.3) (Table). The median OS was significantly higher in the F2P patient who never received an FGFR inhibitor (14.8 months, 95% CI 13.2-NE) vs F2FN group (9.6 months, 95% CI 5.52-22.9) (p=0.04). Table: 108P

Median PFS in F2FN and F2P groups based on 1L and 2L therapies

Conclusions

Our study highlights the distinct features of FGFR2 fusion-positive BTC, which is associated with a significantly longer OS despite a shorter PFS on standard 1L chemo. These findings underscore the need for trials to evaluate the efficacy of 1L FGFR inhibitors in these patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Incyte Pharmaceuticals National Cancer Institute.

Disclosure

N. Tran: Financial Interests, Institutional, Funding, Grant K23MD017217-01A1: NIH. M. Borad: Financial Interests, Institutional, Advisory Board: Senhwa, Adaptimmune, Agios, Halozyme, Celgene, EMD Merck Serono, Toray, Dicerna, Taiho, Sun Biopharma, Isis Pharmaceuticals, Redhill, Boston Biomed, Basilea, Incyte, Mirna, Medimmune, Bioline, Sillajen, ARIAD, Puma Pharmaceuticals, Novartis Pharmaceuticals, QED Pharmaceuticals, Pieris Pharmaceuticals; Financial Interests, Personal, Advisory Board: ADC Therapeutics, Exelixis Pharmaceuticals, Inspyr Therapeutics, G1 Therapeutics, Immunovative Therapies, OncBioMune Pharmaceuticals, Western Oncolytics, Lynx Group; Financial Interests, Personal, Other: AstraZeneca. L. Roberts: Financial Interests, Institutional, Advisory Board: Bayer, BTG International, Exact Sciences, Gilead Sciences, GlycoTest, Redhill, TARGET PharmaSolution, Fujifilm Medical Systems; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Exact Sciences, Gilead Sciences, GRAIL, QED Therapeutics, TAVEC. D. Ahn: Financial Interests, Personal, Advisory Board: Advanced Accelerator Applications, Daiichi Sankyo Company , Eisai Inc, Exelixis , Genentech USA, Inc., Ipsen Biopharmaceuticals, Inc , Novartis . T. Bekaii-Saab: Financial Interests, Institutional, Advisory Board: Bayer, Pfizer, Incyte, Ipsen, Seattle Genetics, Genentech, Merck KGA, Merus, Eisai, Servier; Financial Interests, Institutional, Other, DSMB: Merck; Financial Interests, Personal, Advisory Board: AbbVie, Boehringer Ingelheim, Janssen, AstraZeneca, Daiichi Sankyo, Natera, Celularity, Exact Science, Sobi, BeiGene, Xilis, Foundation Medicine, Stemline, Blueprint, Celularity, Caladrius, Glaxo SmithKline, Deciphera, Zai Labs, Illumina, Sanofi; Financial Interests, Personal, Other, DSMB: AstraZeneca, Exelixis, The Valley Hospital, Fibrogen; Financial Interests, Personal, Other, DSMC: PanCAN; Financial Interests, Personal, Royalties, WO/2018/183488: HUMAN PD1 peptide vaccines and uses thereof – Licensed to Imugene: Imugene; Financial Interests, Personal, Royalties, WO/2019/055687: Methods And Compositions For The Treatment Of Cancer Cachexia – Licensed to Recursion: Recursion; Financial Interests, Institutional, Research Grant: Agios, Arys, Bayer, Amgen, Ipsen, Clovis, Pfizer, Celgene, Novartis, Arcus, Atreca, Mirati, Merus, Abgenomics, BMS; Financial Interests, Institutional, Coordinating PI: Boston Biomedical, Incyte; Financial Interests, Institutional, Steering Committee Member: Seattle Genetics; Non-Financial Interests, Advisory Role: Imugene, Sun Biopharma. All other authors have declared no conflicts of interest.