Real-world outcomes of first-line gemcitabine–platinum plus an immune checkpoint inhibitor and subsequent treatment with matched targeted therapy in biliary tract cancer

Background Gemcitabine plus platinum combined with an immune checkpoint inhibitor (GP-ICI) is standard first-line therapy for advanced biliary tract cancer (BTC); however, tumor-site distribution, molecular epidemiology, and postprogression treatment access vary globally. We compared real-world outcomes and postprogression treatment patterns between US and South Korean tertiary centers. Patients and methods Patients with advanced BTC receiving first-line GP-ICI at MD Anderson Cancer Center (MDACC) or Asan Medical Center (AMC) between 2021 and 2025 were retrospectively analyzed. Outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and postprogression survival (PPS). Molecular profiling and treatment patterns were evaluated. Results Among 375 patients (MDACC, n = 121; AMC, n = 254), intrahepatic cholangiocarcinoma was observed at a higher proportion at MDACC (71.9% versus 42.1%), whereas extrahepatic cholangiocarcinoma was more common at AMC (10.7% versus 41.7%). ORR (21.5% versus 15.7%), median PFS (6.6 versus 7.2 months), and median OS (19.5 versus 14.9 months) were comparable. Median PPS was significantly longer at MDACC (13.1 versus 5.8 months; P = 0.002). IDH1 mutations and FGFR2 fusions were more common at MDACC, whereas HER2 alterations were more frequent at AMC. Among patients with actionable alterations, matched targeted therapy was administered more frequently at MDACC (75.8% versus 12.8%; P < 0.001) and was associated with significantly longer PPS [hazard ratio (HR) 0.15, 95% confidence interval (CI) 0.06-0.41, P < 0.001] and a trend toward longer OS (HR 0.54, 95% CI 0.26-1.10, P = 0.089). Conclusions Real-world GP-ICI outcomes were comparable between US and South Korean cohorts. The differences in molecular profiling, matched targeted therapy utilization, and postprogression outcomes underscore the need for broader molecular profiling and improved targeted therapy access in advanced BTC.