EvidenceExtrahepatic cholangiocarcinoma (perihilar and distal)

A direct check of the HERIZON-BTC-01 testing algorithm in routine pathology: IHC 3+ can stand alone, 2+ needs ISH, and the low-level amplification in weakly stained tumours is the group where HER2 drugs are least likely to help.

A lower, more conservative prevalence than the 2017 meta-analysis, using the trial's own definition. Heterogeneity means a small biopsy can miss HER2, which argues for testing resection specimens and for reflex testing rather than testing on request.

Durvalumab with gemcitabine-cisplatin is a first-line standard for advanced biliary tract cancer, with pembrolizumab (KEYNOTE-966) as the alternative.

Adjuvant capecitabine is the standard after resection of intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, endorsed by ASCO and ESMO guidelines.

The prevalence estimate that made HER2 the first gallbladder-relevant target; it argues for testing every advanced gallbladder cancer, since one in five may qualify for zanidatamab or trastuzumab deruxtecan.

The clearest early head-to-head of the three biliary sites on one platform: for gallbladder cancer it made HER2 the target to test for and showed that IDH and FGFR inhibitors would rarely apply.

This single-arm trial is why NCCN lists chemoradiation after a positive margin or involved nodes. The near-identical survival after R0 and R1 resection is suggestive but unproven; no randomised trial has followed, and the UK does not routinely offer it.

Gemcitabine-cisplatin is the backbone of first-line treatment for advanced biliary tract cancer, now combined with durvalumab or pembrolizumab.