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

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. 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. 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: 108PMedian PFS in F2FN and F2P groups based on 1L and 2L therapiesFGFR2 Fusion NegativeFGFR2 Fusion PositiveNPFS, months (95% CI)NPFS, months (95% CI)1L chemo377.6 (4.6-13.3)215.4 (3.8-9)1L FGFR inhibitor0na47.7 (2.1-NE)1L Overall377.6 (4.6-13.3)255.9 (3.8-8.5)2L chemo2010 (4.6-13.8)95.5 (4.8-19.3)2L FGFR inhibitor0na168.2 (7.2-NE)2L Overall2010 (4.6-13.8)258.4 (7.2-13.8) Open table in a new tab 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.