120P Management of biliary tract cancers in early onset patients: A French multicenter real-life study from the ACABI-PRONOBIL cohort

Biliary tract cancers (BTC) including cholangiocarcinoma (CC) and gallbladder cancer (GBC) are rare cancers with poor prognosis. Few data are available on early-onset BTC (EOBTC) defined as patients (pts) under age of 50. A retrospective chart review was performed in pts treated for BTC in 14 French centers between 2003 and 2021. Data on demographic characteristics, therapeutic management, and molecular profile were collected. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan Meier method. Prognostic factors were assessed by univariate and multivariate analyses by Cox regression. Overall, 1256 pts with BTC were included. Patients with EOBTC (n=188, 15%) had less comorbidities according to Charlson score (63.5% vs 84.4%, p<0.0001), higher tumor stage (cT3-4: 49.9% vs 32.17%, p=0.0126), bilobar liver involvement (47.7% vs 32.1%, p=0.0002) and metastatic disease (67.5% vs 57.49%, p=0.0097) compared to older pts, but did not differ regarding primary tumor location (intrahepatic vs extrahepatic CC vs GBC), WHO performance status (PS 0-1: 94.4% vs 85.5%, p=0.15), and sex-ratio (50.8% vs 53.4% of males). First-line systemic therapy for advanced BTC (n=818, 65.2%) was mostly a doublet by GEMCIS (45.5% vs 32.1%, p=0.0091) or GEMOX (43.3% vs 56.5%, p=0.0091) in EOBTC vs non-EOBTC respectively. EOBTC pts received more frequently a 2nd line therapy (89.5% vs 80.9%, p=0.02). For advanced BTC pts, median (m)OS was 17.0 mo vs 16.2 mo (p=0.08) and mPFS was 5.8 mo vs 6.0 mo (p=0.89), in EOBTC vs older pts respectively. Molecular profiling was performed in 72.6% of EOBTC pts vs 52.4% in older pts (p=0.0019), and less actionable alterations were found (e.g. IDH1 mutations, 7.8% vs 16.6%; p=0.029; FGFR2-fusion, 11.7% vs 8.9%; p=0.029). We did not find any usual prognostic factors in BTC (CEA, CA19-9, PS, neutrophile-lymphocyte ratio, number of extra-hepatic metastases) associated with EOBTC survival. Pts with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage, and have similar PFS and OS in comparison to older BTC pts. Molecular profiling was more often performed in EOBTC pts but less actionable alterations were found.