Durvalumab: A PD-L1 Blocking Antibody for the Treatment of Adult Patients with Locally Advanced or Metastatic Biliary Tract Cancer

Biliary tract cancers (BTCs), comprising intrahepatic, hilar and extrahepatic cholangiocarcinoma and gallbladder cancers, are associated with poor prognoses. The majority of patients present with advanced-stage disease, and systemic treatment remains the mainstay of treatment. Recently, multiple targeted therapies have been approved by the US Food and Drug Administration (FDA), including pemigatinib, infigratinib, futibatinib and ivosidenib for patients whose disease has progressed on first-line systemic therapy. However, there has been no improvement on the first-line systemic therapeutic regimen of gemcitabine and cisplatin chemotherapy in more than a decade. Recently, durvalumab in addition to gemcitabine plus cisplatin was approved by the FDA as a first-line treatment option for patients with advanced BTC based on the TOPAZ-1 trial. The TOPAZ-1 trial was a phase III double-blind, placebo-controlled trial that enrolled 685 patients into a durvalumab plus gemcitabine plus cisplatin arm or a gemcitabine plus cisplatin arm. The trial demonstrated that the addition of durvalumab to standard-of-care chemotherapy was associated with improvement in median overall survival (12.8 versus 11.5 months), progression-free survival (7.2 versus 5.7 months) and response rates (27% versus 19%). The incidence and severity of adverse events were similar in both groups. Durvalumab in addition to gemcitabine plus cisplatin has become the new standard-of-care treatment for patients with advanced BTCs. This article reviews the immunotherapeutic options for patients with BTCs, describes the studies that led to the TOPAZ-1 trial, and summarizes key areas of research that are necessary to inform future drug development and improve patient outcomes.