Gemcitabine-cisplatin + PD-(L)1 blockade in biliary cancer

Gemcitabine plus cisplatin combined with a PD-1 or PD-L1 checkpoint inhibitor is now the first-line standard for advanced biliary tract cancer, including gallbladder cancer. The pairing rests on chemotherapy-induced immunogenic cell death working together with checkpoint blockade in a group of cancers whose stroma is inflamed. Two phase 3 trials support it: TOPAZ-1 added durvalumab and KEYNOTE-966 added pembrolizumab to the chemotherapy backbone, and both were positive, with a modest average gain and a minority of patients who become long-term survivors. No predictive biomarker, whether PD-L1, tumour mutational burden or microsatellite instability, reliably identifies who those long survivors will be.