Biliary tract cancer

The EU has approved 7 indications of 6 drugs in biliary tract cancer. 5 of them need a biomarker result: FGFR (2), HER2 (1), IDH1/2 (1) and MMR/MSI (1). 6 tumour-agnostic approvals also apply when the tumour carries the alteration.

Approved indications, Biliary tract cancer
Drug	Biomarker requirement	Regimen	Setting	Conditions

dMMR / MSI-H1
Pembrolizumab Keytruda		Monotherapy	2L advanced	Disease progression on or following at least one prior therapy

FGFR2 fusion2
Futibatinib Lytgobiconditional		Monotherapy	2L advanced	Cholangiocarcinoma only; Progressed after at least one prior line of systemic therapy
Pemigatinib Pemazyreconditional		Monotherapy	2L advanced	Cholangiocarcinoma only; After at least one prior line of systemic therapy

HER21
Zanidatamab Ziiheraconditional	HER2-positive (IHC 3+)	Monotherapy	2L advanced	After at least one prior line of systemic therapy

IDH1 mutation1
Ivosidenib Tibsovo	R132	Monotherapy	2L advanced	Cholangiocarcinoma only; After at least one prior line of systemic therapy

No biomarker required2
Durvalumab Imfinzi	None	+ gemcitabine and cisplatin	1L advanced	None
Pembrolizumab Keytruda	None	+ gemcitabine and cisplatin	1L advanced	None

Tumour-agnostic approvals6

Approved for any solid tumour that carries the alteration, wherever the tumour started.

Drug	Biomarker requirement	Regimen	Setting	Conditions

EpCAM1
Catumaxomab Korjuny		Monotherapy	2L	Malignant ascites; not eligible for further systemic anticancer therapy

HER21
Trastuzumab deruxtecan Enhertuconditional	HER2-positive (IHC 3+)	Monotherapy	2L advanced	After prior treatment; No satisfactory treatment options

NTRK fusion3
Entrectinib Rozlytrekconditional		Monotherapy	Any line	No prior NTRK inhibitor; Older than 1 month; disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity; no satisfactory treatment options
Larotrectinib Vitrakviconditional		Monotherapy	Any line	Locally advanced, metastatic or where surgical resection is likely to result in severe morbidity; no satisfactory treatment options
Repotrectinib Augtyroconditional		Monotherapy	Any line advanced	Prior NTRK inhibitor, or no prior NTRK inhibitor and treatment options not targeting NTRK provide limited clinical benefit or have been exhausted; Aged 12 years and older

RET fusion1
Selpercatinib Retsevmo		Monotherapy	Any line advanced	Treatment options not targeting RET provide limited clinical benefit, or have been exhausted; Aged 2 years and older

Biomarkers in biliary tract cancer

Label wording7

The sentence from section 4.1 of the SmPC that each indication above comes from.

Pembrolizumab (Keytruda)
unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy.
Pembrolizumab (Keytruda)
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the first-line treatment of locally advanced unresectable or metastatic biliary tract carcinoma in adults.
Durvalumab (Imfinzi)
IMFINZI in combination with gemcitabine and cisplatin is indicated for the first-line treatment of adults with unresectable or metastatic biliary tract cancer (BTC).
Zanidatamab (Ziihera)
Ziihera as monotherapy is indicated for the treatment of adults with unresectable locally advanced or metastatic HER2-positive (IHC3+) biliary tract cancer (BTC) previously treated with at least one prior line of systemic therapy (for biomarker-based patient selection, see section 4.2).
Pemigatinib (Pemazyre)
Pemazyre monotherapy is indicated for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.
Ivosidenib (Tibsovo)
Tibsovo monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy (see section 5.1).
Futibatinib (Lytgobi)
Lytgobi monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.