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

Source: https://onco.cc/pairings/gemcis-plus-io-btc/  
OnCo record `gemcis-plus-io-btc` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Gemcitabine + cisplatin + Immune checkpoint inhibitors
- Type: combination
- Rationale: Chemotherapy-induced immunogenic cell death plus checkpoint blockade; biliary cancers have an inflamed stroma.
- Evidence: Two phase 3 trials.

## Sources

- ClinicalTrials.gov NCT03875235: TOPAZ-1: https://clinicaltrials.gov/study/NCT03875235
- ClinicalTrials.gov NCT04003636: KEYNOTE-966: https://clinicaltrials.gov/study/NCT04003636

## Connected records

- cancers: [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Extrahepatic cholangiocarcinoma (perihilar and distal)](https://onco.cc/cancers/extrahepatic-cholangiocarcinoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Intrahepatic cholangiocarcinoma](https://onco.cc/cancers/intrahepatic-cholangiocarcinoma/)
- trials: [KEYNOTE-966](https://onco.cc/trials/keynote-966/), [TOPAZ-1](https://onco.cc/trials/topaz-1/)
- drugs: [Gemcitabine + cisplatin](https://onco.cc/drugs/gemcitabine-cisplatin/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- key papers: [Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study](https://onco.cc/key-papers/paper-topaz-1-three-year-survival-j-hepatol-2025/)
- roadmaps: [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/)

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