{"entity":{"id":"gemcis-plus-io-btc","kind":"pairing","name":"Gemcitabine-cisplatin + PD-(L)1 blockade in biliary cancer","aka":[],"tldr":"Chemotherapy plus immunotherapy is now the first treatment for advanced bile duct cancer, with a small average gain and a minority of long survivors.","summary":"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.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03875235: TOPAZ-1","url":"https://clinicaltrials.gov/study/NCT03875235"},{"label":"ClinicalTrials.gov NCT04003636: KEYNOTE-966","url":"https://clinicaltrials.gov/study/NCT04003636"}],"tags":[],"related":[],"cancers":["cholangiocarcinoma","gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["topaz-1","keynote-966"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"gemcitabine-cisplatin","b":"checkpoint-inhibitor","rationale":"Chemotherapy-induced immunogenic cell death plus checkpoint blockade; biliary cancers have an inflamed stroma.","evidence":"Two phase 3 trials.","pairingType":"combination"},"route":"/pairings/gemcis-plus-io-btc/","neighbours":{"cancer":[{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"extrahepatic-cholangiocarcinoma","kind":"cancer","name":"Extrahepatic cholangiocarcinoma (perihilar and distal)","route":"/cancers/extrahepatic-cholangiocarcinoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"intrahepatic-cholangiocarcinoma","kind":"cancer","name":"Intrahepatic cholangiocarcinoma","route":"/cancers/intrahepatic-cholangiocarcinoma/"}],"trial":[{"id":"keynote-966","kind":"trial","name":"KEYNOTE-966","route":"/trials/keynote-966/"},{"id":"topaz-1","kind":"trial","name":"TOPAZ-1","route":"/trials/topaz-1/"}],"drug":[{"id":"gemcitabine-cisplatin","kind":"drug","name":"Gemcitabine + cisplatin","route":"/drugs/gemcitabine-cisplatin/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"paper":[{"id":"paper-topaz-1-three-year-survival-j-hepatol-2025","kind":"paper","name":"Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study","route":"/key-papers/paper-topaz-1-three-year-survival-j-hepatol-2025/"}],"roadmap":[{"id":"gallbladder-cancer-roadmap","kind":"roadmap","name":"Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials","route":"/roadmaps/gallbladder-cancer-roadmap/"}]}}