Recent advances in systemic therapy for biliary tract cancer: Evidence from Japan and recommendations in guidelines.

Abstract

Systemic therapy for biliary tract cancer (BTC) has evolved substantially over the past two decades. Gemcitabine plus cisplatin was established as the global standard first-line regimen, followed by further optimization through alternative doublets, intensified triplet chemotherapy, and the recent introduction of immune checkpoint inhibitor-based combinations. In Japan, pivotal clinical trials have played a valuable role in refining treatment strategies, including the establishment of gemcitabine plus S-1, gemcitabine, cisplatin, plus S-1, and adjuvant S-1 after curative resection. Beyond cytotoxic chemotherapy, molecular targeted therapy and tumor-agnostic approaches have expanded treatment options for selected patients in the second-line and later-line settings. Actionable alterations such as FGFR2 fusions, IDH1 mutations, HER2 amplification, microsatellite instability-high status, and other rare genomic events enable precision medicine approaches with meaningful clinical benefit. Despite these advances, prognosis remains poor for many patients with BTC. Ongoing efforts to optimize treatment sequencing, refine perioperative strategies, and integrate comprehensive molecular profiling are expected to further improve outcomes. Continued generation of high-quality clinical evidence and international collaboration will be essential to advance the management of BTC.